final bsci 222

reductionist

modern biology, break things and see how they work individually

westminster tournament roll - england tapestry 1511

roman empire used african troops, british troops into africa, some african alleles in britian british were also slave traders but slavery was illegal in britians - can see black man on tapestry, community of blacks for 800 years also chinese people running trade

Francis Galton

( 1822-1911) galton's interest in mental operation led him to psychometry - the science of measuring mental facilities father of behavioral genetics- ground work laying twin studies, monozygotic and dizygotic twins and inheritance of ability man's natural ability is derived by inheritance- practicable to produce a highly gifted race of men by judicious marriage during several consecutive generations- breed from the best of humanity many accomplishments, pedigree analysis, inheritance of ability, normal distribution famous, knighted , wanted to take control and breed humans like animals wanted to start a british master race with rising powers of germany and america ripped out of the narrative around 1945, accused of being nazi

zygotes missing 1 chromosome

( monosomy), cannot develop to birth- except for females with single x chromosome

a diploid organsim has 2n=36 chromosomes how many chromosomes will be found in a trisomic member of this species?

2n+1= 37

testerone receptor

2 alternative promoters broken , no penale spine, use hydraulics

tetrasomy

gain a pair of homologous chromosomes

outcome of robertsonian translocation

1 metacentric chromosome and 1 chromosome with 2 short arms

polyploidy

1 extra complete set of chromosomes, added because of failure of chromosomes to separate during mitosis or meiosis ( autopolyploidy- 1 species) or because of hybridization ( allopolyploidy) - triploid

all possible uses for stem cells

- care for degenerative diseases such as Parkinson, Alzheimers, and MS - repair spinal cord injuries - treat burn patients 1.) remove skin cells from patient 2.) reprogram skin - ipsc 3.) treat iPs cells so that they differentiate into a specific cell type 4.) return cells to repair damaged tissue

human genome project process

- dna samples were collected from sperm -dna was distributed to 4 in america, and 1 in britian - researchers performed mapping, sequencing, and analysis using specialized equipment cut many genes into random fragments, sequence each fragment , over lap sequence read, over lap continues for a complete sentence 7 days a week for 13 years break up chromosome into 300 base pairs at a time , 1 fragment at a time 2nd and 3rd generation machines illumer- 10,000 little sequences at a time, can do 2 human genomes a day keep overlapping sequences nanopore- can do whole chromosome, small, million bp, can do more in day , than warehouse machines in weeks

why our flat faces?

- speech, we have fat tongue , L shaped , down throat because face compressed, life tongue to make sounds, no Neanderthal could make this sound tongues were initially entirely in mouth, - tongue moved down the throat to provide a vertical section for producing vowels such as ee, ooh, and aah evolutionary benefits of language outweighed increase risk of choking produced by the position of our layrnx and tongue

SEMG2

.91 in us neutral .67 in gorilla, slightly negative, detract from performance but not by much 3.15 in chimp- rapid evolution all about trying to get their sperm through sperm of other males and try to coagulate faster rate of molecular evolution of semg2 correlate with levels of female promiscuity humans can produce it SEMG2 , sufficiently demethylated will get coagulation

heterozygote inversion

1 wild type chromosome and 1 with a para centric inversion in prophase 1- invs. loop forms - metaphase lines up - have to inversion loop to match genes , bump is fragile and hard to achieve gametes: wont happen , loose chromosomes dysfunctional: can be mechanism for speciation- us separating from chimp invs- made successful meiosis more difficult

3 rules for american eugenicist

1.) immigration- took much from eastern europe, less emotionally stable, laughlin 1924 - immigration act- constricted immigration to the US 2.) inter racial : laws prevented this ( white northerners and inbred white southerners- davenport issue, would wreck northern race laughlin passed laws for sterilization at state level in 35 states sterilze through ranking - idiot- imbecile 1941- 36000 american sterilize 1970 stopped 100,000 had been officially sterilized

human brain develop

10 protein coding regions known to be critical for brain size have changed rapidly ( dN/dS>1) in humans best known ASPM - abnormal spindle like microcephaly associated gene regulates the number of times neuronal stem cells can divide, many amino acid changes in higher primates and additional changes in the human sequence humans divide more often than chimps defects are linked with microcephaly - smaller cortex, brain expression of the effectors of ASPM in mice produce expanded brains- died as mouse skull is too small 2 human alleles exist , 1 in people who speak tonal languages( inflection and impart meaning ) and a new allele 5800ya in european and some african language who speak atonal languages, in sumeria at exact same time as atonal language arose variance in human genomes- go to Africa- most diverse people with most diverse culture, can tease apart culture vs genes did atonal languages or the mutation come first? ASPM is also in intelligent animals such as elephants and dolphin

key points of evolution

1000 MYA yeast unicellular biology 500 MYA multicellular biology- drosophilla 65 MYA mammalian biology - mouse need not only human genome but to compare- 1% difference in chimps and us make us human can look at multi cellular lifeforms in context of unicellular yeast

homo sapiens from homo heidelbergensis

125kya in east africa- flat skull, dome 10kya before that still had snout and eye ridge with technology of throwing spear- dome skull with flatter face and lighter bodies, smaller bones, kill from distance , now need politics to talk, laughter came about around this time not in much danger with spear - thin bones, could have larger population - why heidelbergensis replaced

plastic

19 billion pounds of plastic ends up in the ocean every year 90% of sear birds have plastic in their bellies plants can be transformed with bacterial ( alcaligenes- use plastic as their storage molecule - we use glycogen) genes expressing the biodegradable plastic polyhydroxybutyrate (PHB) in its chloroplasts make plastic and degrade it for energy- get bacteria to produce plastic- too expensive - have to feed bacteria- plant can feed themselves took the gene from bacteria and put it into chloroplasts- chloroplasts use sun energy--> sugar chloroplasts with alcaligenes - use the sun to create plastic- plants 1/3 weight in plastic- extract plastic - make biodegradable plastic plants can also make petroleum - bad in thunderstorms , use algae in containers

geneticists manifesto

1939, 23 geneticists used the geneticists manifesto , demanding measures to improve the genetics quality of the human race stated that natural talent could not be assessed in the USA which did not offer equal opportunities to its citizens eugenics did not take in account that complex triats like abilities are multifactorial ( genes, environment, and society )

beginning of biotechnology - evil uses

1970s - E.coli, make insulin- accidentally made bacteria that would kill us now engineer microbes to be more deadly- engineer deadly pathogens- after collapse of soviet union- government cant afford to keep paying scientists, large program to make biological warfare, many went west adinovirus- group of virus that causes colds- engineered to modify collagen gene, gave it to a rabbit, produced auto immune disease that attacked the structure and made it dissolve most deadly product- omega strain fused small pox and ebola , had the infectivity of small pox and massively boosted by killing power of ebola- omega loose-risk

proconsul africanus

1st ape, lived 20-60 mya body like a monkey, arms and legs are the same size chimps have longer arms, we have longer legs gene A1 had duplicated through unequal crossing over 2 copies - 1 can diversity- us and chimp insert this compare orthologs how A1 in chimp has changed compared to A1 in us - find pattern of evolution since species diversified

Genghis Khan

1st mongol empire 1206-1227 major genetic influence , slaughtered males descendants maintained power for 100s of years, males were prolific with harems and concubines todays mongol empire 8% y chromosome identical, .5% of worlds male population identical 16 million descendants

meiosis abnormalities

20% of human fertilized eggs contain chromosomes abnormalities cf2% of mice only 2 % of fetuses with chromosomal abnormalities survive to birth more than 30% of human conceptions spontaneously abort giant panda and mountain gorilla also mess up meiosis theory- too accumulate many recessives other animals:natural/sexual selection weeds out recessives

animal gene gun

20000 lb in ^2 pressure- different sizes for animal organs sapphire tipped gun can shoot atomized droplets of genetic matieral through the skin and directly into test animal quickly used in china for colon cancer- insert into anus australia- immunize sheep, large scale - gold particles have genes with antigens- viruses, antigenic gene expressed in sheep cells- produce viral proteins - immune response to viral proteins

triploid

3 of every chromosomes- occur by fertilization of 2 sperms birth rare- abnormal survive for a few hour- usually mosaic

pedigree collapse

30 generations ago 1.07 billion ancestors , more than world population at the time, worlds population was only 100,000,00 with 281,474,976,710,656 descendants indicates massive redundancy

rapid changes in regulatory sequences

4 distinct mutations confer adult lactose intolerant in different populations

interbreeding

40kya- neanderthals account for 2% of the genes in non-africans - we each carry different parts of the neanderthal genome , neanderthal genetic variants influence modern risks for disease resistance, depression, heart attacks , nic addiction several neanderthal genes associated with skin phenotypes under positive selection 18 genes ( several related to Uv radiation ) within the 3p.21.31 region of east africans -chromosome 11 UV genes - in asians but not europeans, europeans burn more easily, developed in neanderthals during ice age from sun off ice europeans it deeply wooded area lost it europeans , asians and people from oceania have the same amount of neanderthal dna - europeans co existed with neanderthal without breedings

sialic acid

45 genes involved in sialic acid metabolism are disrupted or have altered function Alu element , transposable jumped into gene and knocked it out which allowed the brain to grow

crohns disease

5 snps that increase the risk of crohns are recognized by a group of transcriptional activators called GATA 2 gwa study, disease in bones but associated with inflammation of the gut

many genes in haplotype

5% of our rapidly evolving regions dont contain genes, look for enhancers or other regulatory regions regions selected for - contain many genes- which has been selected for? - do integrated genetic population analysis mouse models: ectodysplasin receptor- most people in asia have mutation, single amino acid change, radical missense, mouse with european allele and ouse with asian allele, asian - hair thicker, mammary small, sweat glands EDAR- asian warlords favored thick hair- sexual selection

finding trait in genome

6 billion nucleotides, few nucleotide difference between those who have trait and those who don't - cut dna into manageable pieces- map genome can use RFLP

ancient mammals

70-80 MYA mammals in dinosaur time, big fat teeth fused together , extinct with dinosaurs, a few mammals and birds survived and everything is descended from them now mouse tree shrew- primitive characteristics - look like first ancestral mammal shrew survived- great lineages from small ancestors can compare genomes and see what defines us as mammals can also look what makes mouse and humans different - line up 3 billion bp - computer can go back and forth and see what is conserved and what is different

charles charlemagne

800 ad tried to revive roman empire, had many sons, all descended from him, indicates pedigree collapse

malaria

800 years ago began to chop trees, left tree stump , accumulate water, mosquitos, malaria, then the disease killed 1/2 of everyone thats ever lived , alleles of everyone are marked with resistance to malaria

why do women have more non-disjunction?

90% eggs males- continue to do mitosis , replenish themselves- 80 year old man is still producing semen women- about 400 eggs, stores in prophase older mothers are more likely to give birth to a child with down syndrome- at age 40-1/100 down syndrome - there are lives birth most embryos with down syndrome never get to be born - spontaneously aborted at age 50- 90% are aneuploid sperm will hit egg and divide a few times- then spontaneously abort

epigenetics in human , neanderthals and denisovians

99% of the epigenome was identical across us, neanderthals, and denisovians about 700 regions vary, in more than 200 of these , neanderthals and denisovians shared the same methylation pattern while humans had the opposite - this says 2000 different methylated regions (DMR) , substantial methylation changes in the HOXD cluster, may explain ancestral differences between archaic and present day humans - genes that varied in neanderthals were in morphological genes- HOXD

Humans and Neanderthals

99.5% same , neanderthals were lactose intolerant, lacked penile spines, had red hair and the same FOXP2 sequence that we have HARS are highly conserved in neanderthals runx2 sequence is similar to a mutation in humans that leads to a bell shaped rib cage- has to different promoters, for ribs, face, nose , one different in protein production larger , bell like chest cavity, wider pelvis, compact, no waist- possible adaption against the cold complex social interaction- protected wounded neanderthals , - marked red hand on cave dated 70k years - wanted to be known MC1R red hair

humans to each other

99.9% similar to each other, 3.5 million SNPS distinguishing us, know very little about indels between humans and different size genomes between us

first transgenic primate

ANDi was produced by microinjecting a provirus into an egg

result of conjugation between cells with different F factors

F+ *F- = 2 F+ cells Hfr * F- = 1 Hfr and 1 F- - entire chromosome would have to be transferred F'+F-= 2 F- cells

eugenic rating

B+- greater , given medal, and certificate, couldnt marry into families without the certificate- stamp of genetic worthiness

plant GMO/ corn

Bt corn synthesize an insecticidal toxin gene from Bt bacteria corn has been genetically modified to resist insect infestation make use of cry gene in bacillus thurigenes Bt , this gene directs the production of a protein that causes paralysis and death to many insects also make Bt cotton - modify its codon gene , use new promoter corn root worm - insecticidal resistance but not resistant to Bt toxin

BTK serial killer

Dennis Rader and Adam Lanza, killed 20 children and 7 adults must have genetic changes for such crazy behavior can cause an issue as this stigmatizes people who have never committed a crime,

ectodysplasin A receptor

EDAR plays a crucial role in the development of hair teeth and exocrine glands cascade that results in activation of a TA EDAR chinese variant , 30kya, 3710A- introduced into mice produced shovel shaped teeth, thicker hair follicles, smaller breasts, and increased number of sweat glands- variant 370A

characteristics of E.Coli cells with different types of F factor

F+- f factor is present as separate circular plasmid, is a donor in conj. F-- f factor is absent, and is a recipient in conj. Hfr- f factor is present but integrated into the bacteria chromosome, is a Hfr donor in conjugation f'- f factor is present as separate circular plasmids, and carrying some bacterial genes- donor in conjugation

green fluorescent protein

GFP - RFP, widely used some fluorescent natural , can be engineered for variation - brainbow- transgenic mice, neurons with multiple distinctive hues- in hippocampus- short term to long term memories- mice in basic environment- no stimulation, mice in complex environment- see neurons and interconnections in hippocampus , nerve cells randomly express fluorescent proteins of different colors , combinations of these proteins labeled neurons with distinctive hues discovered: stimulated vs unstimulated mice - huge difference in size and complexity of hippocampus neurons taxi driver: know all streets in london -reproduces mice with stimulus used for highlighting specific structures and to observe cells overtime expressing one or more proteins tagged with fluorescent protein

genome-wide association studies

Gwas, finding alleles for general conditions polygenic inheritance, have all genome variants on one side and all phenotypes on another what each SNP could be associated with linked to diabetes: 9p21 , cell growth regulator, banding pattern odds ratio1.2, not previously linked to diabetes, but finding genes we already know are involved validates screening

mein kopf

Hitler said US had right ideas about eugenics studied laws of several american states immigration and reproduction laws

insertion sequences

IS3 and IS2- control insertion in to the bacterial chromosome and excision from it , transposable elements with direct repeats- transposase recognizes these- have direct repeats in the chromosome , it can insert right into the chromosome insert into host- have to have insertion sequences and IS3 and IS3 transposons- composite can also jump

convergent evolution

populations that independently experience parallel environmental changes represented replicated natural experiments

Dr Kary Mullis

PCR, want dna from the gene to study it- in PCR polymerase runs back and forth across genomic dna to mass produce dna - can get dna from someone who has the condition mass produce

sterilization supreme court case

VA, carrie buck raped by cousin, had child - vivian, 3 investigated by eugenic field researcher- estabrook, noted all were feeble minded included 7 month old vivian , laughlin produced pedigree for evidence, carrie buck fought back upheld by supreme court for sterilization - Chief justice holmes- 3 generations of imbeciles are enough

MC1R

a receptor that acts as a switch between production of red pigment pheomelanin and the black and brown pigment eumelanin MC1R from neandtherals showed a point mutation not seen in modern humans, when the mutation was produced in humans cells - impaired MC1R- red hair and pale skin in modern humans - although humans today have a different mutation we all start have with red hair

CRISPR

a bacterial immune system, stretches of bacterial dna with palindrome , included spacers- that was phage dna,- from a virus that had previously infected bacteria CRISPR associated proteins (CAS ) are enzymes that cut DNA and CRISPR is a collection of viral DNA sequences that tell Cas-9 where to cut , bacteria use Cas enzymes to grab fragments of viral DNA- insert the virus fragments into their own CRISPR sequences Cas come along and cut viral dna, picks up pieces of dna and scans genome, find matching dna and cuts it up when another virus comes along, the bacteria can use CRISPR sequences as a cheat sheet to recognize the invader CRISPR regions can fill with viral DNA- repersent the enemies the microbe has encountered can use RNA synthesized to match a target DNA sequence to guide Cas9 ( from Streptococcus) to the right spot in the genome- easier than techniques for gene editing, can repair a faulty gene by cutting it out with CRISPR/cas9 and injected a normal copy of it into a cell- replace viruses

HAR 2

a neural specific enhancer with 12 human substitutions in a 119 base pair segment , drives gene activity in the wrist and thumb during fetal development where as the chimp version cannot- favoring the dexterity to manufacture complex tools stronger and shows a broader pattern of expression than the chimp sequence a response elements for many different transcriptional activators , attach to LacZ , see where it is active- hands , drives expression of genes as a master control- massive impact chimps need differnet hand to go though three

cranid

a program that deduces racial characteristic based on measurement of the skull cheddar man - 14% west asian and 82% west European measures parameter, features, produce racial background easy between asian and european skull asian -broader, wide zygomatic arches , rounder eye socket 9kya- europeans still looked asian, cheddar 14% west asian white skin 9kya- with agriculture, before that homosapiens were all dark skinned neanderthals were only light skinned hominid

generalized transduction

a random fragment of host DNA is packaged in the virus in place of the virus DNA/lytic cycle dnase degrades dna, some dna does not degrade, same size as vira dna, proteins assemble around anything of right size, virus assembles around host dna ,dna comes from anywhere- generalized bacteria are infected with phage and bacterial genes become incorporated into a few phages

bacteriophage

a virus that infect bacteria, - has syringe to inject genetic material virulent phages reproduce through lytic cycle and always kill host cell quickly temperate phages- inactive prophage- phage DNA integrates into bacterial chromosome, genetic material into host- similar to HFR- not better HIV- lysogenic

genetic drift

act on the genetic variation in the gene pool to change the frequency of alleles random fluctuations of allele frequencies from generation to generation are more likely in small, isolated, populations, island populations/ socioreligious groups or following a genetic bottleneck- small samples are less representative range of variation we are left with now , mtDNA in modern humans and compared with chimps and gorilla- have more variation than we do chimp and 1st cousin are more distantly related than us and most distantly related person in the world , we are all very close related- seem different because we are prone to changes that affect appearance

STAT2

affect the immune system found in about 5% of Eurasians and 54% of Papuans

trisomy mosaicism syndrome

affected individual has a combination of cells with the normal chromosomes # and those with trisomy during mitosis in the zygote after fertilization

POU2F3

affects skin cells known as keratinocytes and is found in about 2/3 of east asians

embryonic stem cells

all cell types with different culture conditions form in embryo in blastocyst pluripotent reproduce in the lab for many years -form cell line

frequency of aneuploid events

all events happen at a random chance, there is not more trisomy in the chromosomes that survive trisomy 22- dont see this because these contain key genes for how nerves are put together

M168

all non africans have a marker 168, coalescence to Eurasia adam , when left africa 60k years ago there was a mutation M89 distinguishes people in middle east, 50kya ( on top of M168) M9- turkey appeared in M89 lineage 45kya near iran m130- arose on m168 en route to Australia 1 successful exit out of africa, 1 man had mutation

crop plants and polyploidy

all polyploid, advantage triploid , pentaploid- sterile - odd number, uneven number to get balanced gametes,- is not possible segregate gamete would have 1 chromosome and 2 of another advantage: diploid banana is full of seeds polyploids bigger, more dna, bigger nuclei, big cell

Hardy-Weinberg equilibrium

allele frequencies will not change in a closed, infinitely large sexually reproducing, diploid, where random mating occurring p^2 +2p1+q^2=1 p=A q=a accumulation of changes in allele or genotype frequencies in a population results from failure to meet the criteria for hardy- Weinberg equilibrium sex by itself will not lead to evolution , only shuffling pre- existing variation

zygotes with 3 of the same chromosome ( trisomy)

also lethal except for some smaller chromosomes with a few number of genes 13,18,21

non-synonymous mutation

alter the amino acid sequence of the protein more likely to be subject to selection rate of non - synonymous mutation dN can change shape of protein , natural or sexual selection

cloning genes

amplifying a specific piece of DNA via a bacterial cell, cloning vector: a replicating DNA molecule attached with a foreign DNA fragment to be introduced into a cell

cloning vector

an idealized cloning vector has an origin of replication , one or more selectable, markers and one or unique restriction sites must contain an origin of replication recognized in the host cell so that it is replicated alone with the DNA that it carries needs a simples cleavage sites for each of the restriction enzyme used should carry selectable markers ( reporter gene) - traits that enable cells containing the vector to be selected manufacture of bulk quantities of genes- usually use PCR to isolate and amplify a gene from a genome - also plasmids that are transformed into bacteria that copy them many times

crispr and human dna

an rna guide molecule can be programmed to match any unique dna sequence in the genome a special enzyme called cas9 can be attached to the rna guide, its job is to find the target sequence of dna run align with the target dna sequence and the cas9 attaches and cuts both strands of the dna double helix dna can be amended with an extra dna insertion or a deletion of defective nda a dna cutting and pasting system that uses a customizable rna to guide a dna cutting enzyme to the right spot on dna CRISPR allows researchers to change, deleted or replace genes

mouse model for non-disjunction

anaphase 1: chromosomes are separating by spindle apparatus, chance of two chromosomes are close together and end up in same cell- chance they might be father enough , but if in same cell- aneuploid

TLR genes

ancient genes that help the system detect bacteria, fungi , and parasites

fish genetic engineering

aquaculture, major food source, shrinking , selected for smaller fish through fishing, smaller fish can slip through nets, only 100 full sized cods left in the world now fish farms- can introduce genes in salmon that make it larger ocean pout- very cold waters, promoters work in these conditions, took growth hormone from salmon and ocean pout and put in atlantic salmon - can now grow in the winter standard salmon can only grow in the summer have huge nuclei , grow fish in tanks or net in water salmon eat fish- huge pollution , need antibiotics - genetically engineered fish should not escape - would be bad for environment- in tanks 2015- FDA approved advantage salmon-enetically engineered

negative eugenics

avoid breeding from the worst

BACS /MAC

bacterial artificial chromosomes mammal artificial chromosomes- includes telomere at both ends, a centromere, an origin of replication and a poly linker site to deliver huge quantities of DNA

personalized medicine

based on individual patient - will know if you are protected from high fat diet or not instead of evidenced based medicine which is treating diseases based on large population studies , know that some people wont help

RFLP analysis

before PCR- comparison of set of restriction fragments , produced by DNA from different individual sites recognizes by restriction enzymes may be different in different individuals, look for restriction fragments that are only found in people with a phenotype-genetic marks for the location of the disease causing allele- genetic mark is a chromosome landmark whose inheritance can be studied

darwin

believed that diligence and drive are just as important as intelligence heritability is higher for drive than intelligence related to francis galton more than cousins because of inbreeding

hybrid product of polyploid plants

best of both plants, will not have harmful recessives, heterozygotes, picks best genes - inherited

blindness with genetic engineering

blindness affects 45 million people throughout the world, genetic engineering is now being used to treat patients with Leber congenital amaurosis, a genetic form of blindness homozygous mutation gene is put into adino virus, and injected into the retina of cells, vision improved

tallest/smallest people in world

bone structure- tallest people in world- sexual selection smallest people in world- natural selection african pygmy- benefits to be small in highly humid climate

inversion

break in chromosome and that fragment is inverted and rejoined instead of being lost , - do not involve loss of genetic material and unless breakpoints disrupt an important gene - can have normal phenotype- fragments gets put back in by dna repair system-upside down pericentric- will be folded up too, less active variation in human genome- there is no typical human genome

positive eugneics

breed from the best

de- extinction with crispr

bringing back animals by working with close relations 95% genome of mammoths similar to asian elephant, tweak genome- reproduce mammoth and surrogate mom church- allele replacement , mammoth - low temperature - altered hemoglobin- active at low temperature, more fat , allele for extra fat and allele for thick hair also want to de extinct , neanderthals, human stem cells flooded with neanderthal dna , inserted 15 mammoth alleles into DNA of asian elephants and can place hybrid cells in an artificial womb

positional cloning

by identifying sites that are inherited together with a disease, can locate responsible gene, huntingtons disease, cystic fibrosis, BRCA1 and BRCA2 even though they dont know what the gene is still need to chromosome walk to gene

cas-9

can be precision guided weapons copies the genetic material in each spacer into an RNA molecule, then take up one of one of the RNA molecules, viral RNA and Cas enzymes drift through cell- encounter genetic material from a virus that matches , CRISPR latches on tightly , cause enzymes than chop dna , and prevent virus from replicating

dna coated gold particles

can be shot into plants with air gun or electrical discharge ( gene gun) - can also be used for organ targeted gene therapy of animals

plasmids and customization

can be used to customize bacteria researchers can insert desired genes into plasmids , creating recombinant plasmids as the recombinant bacteria multiply as do the foreign genes, plasmid and the foreign dna are cut by the same restriction enzyme , when mixed the sticky ends anneal joining the foreign DNA and plasmid nicks are sealed in the sugar phosphate bond with DNA ligase

3 major classes of stem cells

can be used to treat diseases 1.) totipotent- can form entire organism, 8-16 mammalian cells, clone farm animals, produce entire organism 2.) pluripotent- embryonic stem cell, become any tissue type, develop through further division , cells on the outside form the placenta , cell in middle becomes pluripotent 3.) multi potent - adult stem cell , can become specific cell types, unipotent

surrogate mother for cloning

can create in vitro- biological uterus - stem cells grow in molds to produce uterus - fertilized egg in this implant human can stay in for 6 days -law animals can stay longer - mass produce with mechanical uterus

HindIII

can cut both a human and elephant dna and and join it together with ligase to form recombinant DNA

cancer and crispr

cancer therapeutic targets using CRISPR- cas9 screens crispr screen of cancer genes, disrupting nearly 20,000 genes in over 300 cancers, from 30 cancer types to uncover which genes are critical for cancer survival scientists identified several thousand key cancer genes

virus and recombinant bio technology

capsids- dna surrounded by proteins, existence independent of the host's cell destroy the cell because they can exist outside

making human GAA to treat glycogen storage disease ( pompe disease )

casein promoter - expressed in milk alpha glucosidase gene - treat pompe disease, glycogen in liver- without enzyme glycogen cannot break down- die if injected with alpha glucosidase- survive milk bunny

dolly- first cloned sheep

cell from mammary glands used as nucleus - thought it had undifferentiated cells- wrong cultured mammary cell in nutrient poor conditions some cells totipotent- could produce whole organism - de methylation occurs in nutrient poor conditions - without methyls gene can express 2nd sheep - egg cell donor, de nucleated, fuse mammary cell with de nucleated egg cell - electrical charge - embryo -cells divide , 8-16 cells , totipotent plant embryo in 3rd sheep - surrogate mother sheep identical to mammary cell donor when frog egg cell divides- no longer totipotent mammalian cell divides- totipotent

M45

central asian y chromosome marker ancestor to europeans, chukchi - best adapted to ice age ate seals and domesticated wolves to colonize west we have many mutations superimposed on m145

MYH16

change in muscle protein , 2 base deletion in myosin gene, the mouth used to produce a muscle that produced the sagittal crest , once we lost muscle did need sagittal crest skull is now round, lost mechanical efficiency , bone could be cracked my muscle needed flat skull, allowed brain to grow homo habilis - 2.4 million years ago made the protein less effective primates , massive jaw muscle shrank , made a 3 fold expansion of the brain possible, when gene broke allowed mutations to accumulate part of 1/6 genes involved with pedomorphism of head knocked out 6 major genes australopithecus - ancestor , had gorilla vs , human like pelvis, hands teeht, and a chimp foot

aneuploids

changes in number of individual chromosomes can be produced by non-disjunction disjunction-successfully separate homologous chromosomes non- disjunction fail to separate- 1 cell gets both chromosome- gets two copies of each gene occur more than often 90% during egg formation than during sperm formation become more frequent as women age nullisomy- loss of homologous pair of chromosomes trisomic- three chromosome monosomic - one chromosome

sorcerer II- global ocean sampling expedition

characterization of viruses within aquatic microbial samples cruise the world, collect 90-200 L of sea water from each of 37 different stations record PH, salinity, temp of water pass water through filter and store at 20C until shipment from next port - filtered different kinds of bacteria discovered 60 million new genes by trolling the oceans - mostly viruses but because of transduction had genes from hosts attached to them

artificial gene synthesis

chemical synthesis of a DNA sequence that represents one or more genes provides a method to efficiently produce long stretches of natural and non-natural nucleic acid sequences, broadening the scope of biological experiments, non natural gene sequences can be synthesized

translocation

chromosome rearrangement between non homologous chromosomes detected by karotype reciprocal : 2 non- homologous break and exchange fragments, two chromosomes sharing non reciprocal: genetic material moves from one chromosome to another

7% of us do not make any functional CYP2D6 enzyme

codeine provides no pain relief 30% of arabs cant make morphine and 10% of European one of the P450 genes, codeine is broken into morphine by CYP2D6 enzyme when we domesticated plants we ate less toxins, genes are no longer used, mutations accumulated in our defenses

paralogs

comparing homologous gene in the same organisms / species arise from gene duplications

transformation

competent cells: cells take up DNA transformants: cells that receive genetic material genetic material : co-transformed , cells that are transformed by 2 or more genes 1.) a donor cell dies 2.) a fragment of DNA from the dead donor cell binds to DNA binding proteins on the cell wall of a competent , living recipient bacteria 3.) the Rec A protein promotes genetic exchange between a fragment of the donor's dna and the recipient DNA bacteria not doing well in environment- bacteria in past could live there- had the dna- dna in plant or animal that would allow the bacteria to adapt- produces recombinant proteins - suspicious its viral dna its taking up - methylates it- viruses dont have methylated dna- insert into genome in place of dna that is no use of it - and see if it survives better

gene transfer in bacteria

conjugation- natural gene transfer and antibiotic resistance, direct transfer- 1 way from donor to recipient, not reciprocal antibiotic resistance comes from the actions of genes on R plasmids that can transfer naturally- r= resistance became widespread in the last 70 years since beginning of widespread use of antibiotics transfer is not limited to bacteria of the same or related species bacteria dying from antibiotics- can get r-plasmid- copies and turns on - if r- gene was on chromosome would have to copy whole thing started use antibiotics to find bacteria with R plasmid mass of antibiotic resistance genes- MRSA can be identical bacteria species but vary in plasmids

haplotypes

conserved blocks, separated by recombination hot spots, less likely to be separated if between hotspots, SNPS can proxy haplotypes- short cuts snps can be represented by other snps, use to follow recent rapid evolutionary change - have tag snps that are proxy to the others- strong correlation between snps - can associate snps with diseases- use RFLP markers for certain diseases linkage disequilibrium , chromosome from mom and dad- recombination hot spots expect crossing over - can be closer but more likely to be separated- linkage disequilibrium a million bp may separate recombination hot spots - haplotype list all the snps 8000 years for haplotype to break down

510 regulatory regions

conserved in chimps, monkeys, chickens, and mice are lost in us many involved in steroid hormone signaling and neural function sensory whiskers and penile spine alternative promoters are deleted from the androgen receptor gene

minimal bacterial cell

contains only the gene that are necessary and sufficient to ensure continuous growth under ideal lab conditions craig venter created learn what it takes for life starting point was mycoplasm mycoides -syn 3.0- operates on 473 genes, 1/2 of the number of genes found in the wild bug and has the smallest set of genes in any organism out of 473 genes 41% contained genome expression information , 18% cell membrane, 17% cytosolic metabolism and 7% dna repair 149 genes were not assigned biological function, conserved , 1/2 genes we have - do not know what they have, didn't know we had them until- human genome can defrog the genome, re-engineer the genome in a more logical function, align common pathways- all genes in dna replication together and can now build more complex cells with difference modules for each activity - minimum genomes went out to people - who can add most existing modules? - infinite variety of genes to put together biological machines of the future

Fire

controlling our own evolution important conquest of FIRE - more than 1mya then agriculture revolution 10kya mode foods high in starch more accessible fire led to improved nutrition from cooked proteins- without meat the protein hungry brain would have been an expensive luxury, had to adapt genetically to food, protein encoding genes under positive selection in humans can eat food pre digested- no longer need huge teeth and massive jaws to grind vegetation and no longer need massive guts to digest vegetation homo erectus invented

new strains of flu virus / swine flu

created by reassortment of genetic material when they effect some hosts - contain many strains of virus generalized transduction- created by reassortment of genetic material rna from human, avian, swine, are all in the same cell- capsid around all rnas- in combination becomes deadly - swine flue

clone carrot from a single carrot cell

cross section of a carrot- use gene gun - small fragments grown in nutrient medium- stirring causes single cells to fall off plants, all cells are totipotent, single cells free in suspension begin to divide, embryonic plant developed from a cultured single cell- 1 cell =1 carrot

insect resistance tomato plant

cut out the gene insert gene into a vector with a selectable resistance marker gene copy vector in bacteria coat tungsten or gold particles with DNA vectors load vector coated particles onto bullet- gene gun shooting the gene gun releases the particles at a high velocity penetrating the plant cells, vector enters the cells , genes are incorporated into the plant genome cells are plated on a selective antibiotic media , only cell with vector will survive

rate of selective pressure

dN/dS=1 neutral ( genetic drift) , doesnt matter if amino acid changes, not important protein dN/dS <1 negative selection , selection against changes in sequence dN/dS >1 positive (darwinian ) selection selection for changes in sequence ,change is good, will lead to rapid change in dna sequences what we look for comparing genomes language of molecular evolution

state fair eugenic exhibits

davenport design, guinea pig showing inheritance, showed eugenic marriages would breed out most unfitness in 3 generations, what you really are has been settled since birth selected parents : better children, warehouse at fair, 3.5 hour examination for IQ, emotional stability, and ( athleticism , developed by James Naismith, creator of basketball, racist) judge human livestock - family evaluation and individual evaluation

emerging from africa

descended from 70-100 people who left africa 50-60 kya, many left africa but only this one successful surveyed genomes of 787 from people around the world

ethical questions of bio engineering

designer babies, with engineered children can create a separate subspecies of humanity trans humanist: life is short we should improve by engineering , fundamentally transforming the human condition by developing technologies that will greatly enhance intellectual, physical, and psychological capacities - ethical questioning if this is eugenics government shouldnt be involved , we make our own eugenic decisions to enhance families

brownian evolution

developed technology, fire , milk cheese with lactose, and mutation in 1 person had a selective advantage people died because they could not compete

P450

different alleles for P450 can be broken down into extensive, intermediate or poor metabolism of medicines between percentages of different races metabolism is if the medicine can be broken down into its useful form

evolution

differential survival of alleles genetics and time, accumulation of changes with selection we have less variation pathogens was one of reason early human beings do not get to breed

genetic recombination with us

dna and virus are good at mixing and matching our own dna- recombinant bio technology gene creatures- need hard drive, plasmid, virus and transposable elements

transformation- simple

dna is present in the medium taken up by the bacteria

synonymous mutations

do not alter the amino acid sequence of the protein selectively neutral background level of random mutation rate of synonymous mutation dS pseudogenes- mutations here do not count, not selected for or against accumulate 4 nucleotides per site per billion years silent ( actin - important protein, cytoskeleton , low non-synonymous rate, high synonymous rate - mutations are random, amino acid substitutions must be disadvantageous ,especially in conserved gene evolution kills off non- synonymous mutations

para centric inversion

does not involve the centromere

ancestors

double every generation a(g)= 2^g after 32 generations exceeds the number of living humans

trisomy 21

down syndrome 3 copies of chromosome 21 300 genes- none of them essential, affect how brain cells connect- DSCAM, genes in circulation- die early of heart realted conditions, sterile, live longer than any other trisomy translocation of chromosome 21 onto another chromosome results in familial down syndrome phenotypically normal but can produce children with down syndrome

cloned genes with plasmids

e.coli - workhorse of all biotechnology and plasmid - cell easily manipulated, transform E.coli, put plasmids into E.coli- mass produce Dna Dna with EcoR1 site and plasmid with EcoR1 sites, cut both gene of interest and plasmid with EcoR1 plasmid opens up , complementary sticky ends, anneal- low temperature, dna ligase to glue- recombinant DNA- human dna is integrated into a bacterial plasmid electroporation - plasmid with origin of replication, replicates , put E.coli in nutrient conditions 37 degrees, temperature of the gut- turbid suspension of E.coli cells- each have about 40 plasmids, centrifuge them , extract plasmids- each copy with copy of gene

bacteria in gut

e.coli, salmonella, have F plasmids , narrow range like related bacteria single mutated genes can pass through millions through mating bridge f- plasmid: contains a number of genes that regulate transfer into the bacterial cell, replication and insertion into the bacterial chromosome

EcoR1

eco- from e .coli 1- first found cut with sticky ends- palindromic- only at this sequence would they eventually reattach denature come apart again

trisomy 18

edwards syndrome ( 47+18) lethal in 2 weeks

buster martin

englands oldest worker, marathon at age 95 cigarettes, drank many cytochrome P450 genes, all well-elderly have them , detoxifying poison , mice have more of these genes than we do can eat more , eat what would kill apes zip code doesnt apply to him because he has protective alleles

differences in genetically identical animals

epigenetic events , litter will not be identical looking

position effects

euchromatin , heterochromatin- different methylation

founder effect out of africa

expansion out of africa sampled only part of the african gene pool - founders effects, we lost bio diversification establishes a pattern of variation common to all non africans eurasia - more drift accumulated because the subsets of the local gene pool carried forward by migrants became successively more homo- less heterozygosity bottleneck- most of us died 60k year ago

F' cell

f factor is present as separate circular plasmids, carrying some bacterial genes can come from an Hfr cell when the f factor excises from the bacteria chromosome and carries bacterial genes with it during conjugation the F factor with the lac gene is transferred into F' cell - producing a partial diploid with 2 copies of a gene

Homo heidelbergensis

first appeared 800kya immediate predecessor to neanderthals, denisovians and humans had a typical cranial volume of 1100-1400 cm^3 - overlaps 1350 avg. of modern humans avg H. sapeins had a larger brain than heidelbergensis, and a smaller brain than h. neanderthlas last CA of us and neanderthal large muscles and brain, fought very close to enemy had long snout and teeth spaced out, no tooth decay as food could slip out , large ridges to protect eyes, and sloping skull to get brains out of the way our skull: over eye ridges, vulnerable for attack ,v

adult stem cells

generate a limited number of cell types with different culture conditions differentiated adult cells can be reprogrammed to form induced pluripotent stem cells (iPSCs) which are capable of differentiating into many different types of cells present in adult body

human artificial chromosomes

formed from truncated chromosome 14 or 21 can make completely artificial with synthetic dna cassette chromosome: upgraded system, destroy chromosome - puts thousand genes into a cell can use with gene therapy - if you cannot put gene into chromosome without disrupting it

y chromosome haplogroup with british surnames

founded 700 ya compared to a group of men with different surnames y chromosome haplogroups for names common in england smith vs control- first was anyone was blacksmith, close representation of haplogroup of england specific names--> same haplogoups in y chromosome except what was illegitimate

races

founded by small populations with different combinations of alleles- genetic drift, sampling error "chance" european population established by 5-7 clans ,populations were isolated - mountains

genome editing

generate rna guide- doesnt need to be phage go along dna searching for match with sequence and cut it , cas9 enzyme- biotechnological purpose, opens up dna , rna aligns, extra dna - repair systems normally join dna with a piece of extra dna customizable rna

orthologs

genes in different species that evolved from the same gene in a common ancestor

recombinant dna techniques

genetic engineering, each of ca.800 Type 2 restriction enzymes cuts a different combination of nucleotides name after source- such as E.coli- tools to cut genes- restriction enzymes - originally isolated from bacteria tool that puts it together- ligase, glue

pharmacogenetics

genetic variation that underlies our responses to chemicals TT and Tt find PTC bitter- find broccoli ( has carcinogens but also protective alleles fro cancer) bitter, and have more food dislikes- tt cant taste PTC- how pharmacogenetics worked many alleles for 700 function food/taste/ odor, live in a world with slightly different smell likes and dislikes could be to avoid poisonous foods, balanced polymorphism - times are good , good plants- beneficial to be a taste and selected the best plants times are bad- ideal not to be a fussy eater, mixed population the best

nancy whexler

genetic way of learning about human disease gene- do not need to know about gene- huge pedigree- search sequence of dna that only people with trait have- need landmarks in gene- with restriction map and with enzyme that cut at specific sites in genome

germ line gene therapy

genetics engineering and enhancement gene therapy ( enhance traits such as intelligence and athletic ability) - not currently legal because of ethical issues can permanently solve problems if kid is short and it will be injected with growth hormones, hormone from transgenic goat, milk has hormone, but short people have fewer cancers 90% of growth hormones are given to boys but if you gave him gene for heigh and he was able to pass it on - illegal, were giving him product anyway

restriction map

genetics landmarks, location of restriction enzyme cut sites on a piece of DNA, cutting DNA from different people with the same restriction enzymes identifies single nucleotides polymorphisms (SNPs) as they produce segments of different lengths- restriction fragment length polymorphisms (RFLPS) using multiple restriction enzymes produces detailed map of SNPs- 1 nucleotide difference, different pattern in gel

gene therapy cancer trials

give people tumor suppressant gene - P53 china- also use adino virus - but only add a single base pair , frameshift mutation west- gene is not present at all

mass produce clones

go to early embryo, take each cell out individually for a source nuclei transfer- producing production herd quickly egg from tracy ( anti - trypsin in her milk , used to treat cystic fibrosis and emphysema ) divide 8-16 cells - totipotent- take out each cell individually- more eggs , de nucleate, fuse together - divide and put into surrogate

bio steel R

goats are producing BioSteel R recombinant spider silk protein in their milk , Julia Essasis - use transgenic organisms in art can be collected, purified and spun into fibers for applications in the medical , military and industrial performance bulletproof skin - made of spider silk took skin from cadaver- either side from spider silk from spider goats

auroch

great black bull, 8-12kya, big buffalo- dangerous-controlled it by killing most violent and aggressive-selected for docility, cow is now sexually mature baby auroch- can bring back the auroch by finding features of the original and breeding

fluorescent use

green under control of actin promoter- constituent - all cells produce actin, all cells green mice for cancer studies: their immune system genes are replaced by human immune system - put human cancers in mice- look at angiogenesis- mice blood vessels into human cancer- what is producing growth factors- identify genes and mass produced them, naked mouse expressing green fluorescent protein under control of the actin promoter- human cancers that express RFP can be implanted into these mice, cancers will give off red fluorescence now the cancers can be observed and monitored

genetically engineered livestock

growth hormone- somatropin , gene to increase yield and out space disease improve nutritional content of meat

pre 1980s identifying important DNA sequences

had to be very knowledgable about a disease to work out its genetic basis - realized genes could be hunted in a genetic fashion by tracing pattern of disease in families

plasmid with host dna

happens when f plasmid jumps out and has a part of hosts chromosome has come off with the plasmid perhaps the lac operon and the f plasmid transfer

engineered plasmids

has origin of replication can mass produce in E.Coli, poly linker sites- 50 bp long , containing multiple unique restriction enzyme sites- with 1 site for each plasmid- if 5 EcoR1 sites, plasmid would disintegrate selectable marker- allows us to say if recombinant plasmid is in the E.coli, - usually antibiotic resistance- only bacteria with plasmid resistance gene will survive if antibiotics is in the medium can also have bioluminescent genes

golden rice

has the potential to help , prevent 1-2 million deaths each year caused deficiency in vitamin A - death and blindness bill gates grain rice- no B carotene used a whole pathway of genes, synthase from maize , bacteria, control of specific promoter- only works in rice seed

HAR 1

has undergone 18 substitutions over its 118 base stretch , only 2 had changed in the prior 310 million years that separated chickens from apes produces non-protein coding RNA in neurons that develop the cerebral cortex- turns on in stem cells that make spherical hemispheres- thinking part of the brain malfunctions in these neurons lead to abnormal foldings of cerebral cortex ( lissencephaly) HAR1 may have altered ancestral human brain function most diverse sequence between us and everything else completely rewritten in us base pairing becomes more strong as it goes from A-U to G-C , 2 hydrogen bonds to 3 hydrogen bonds- sequence is more rigid 49 most accelerated regions go from weak - strong 77%

chromosome 19 apolipoprotein in E gene (apoe)

has variants e2,e3,e4, that differ by 1 amino acid show snp frequency that may be adaptive in ancient environments E4 common , ancestral, low fat diets, help you survive malnutrition , but homozygosity for E4 increase heart disease and Alzheimer not adapted for our new environment other genes may help alleviate effect e3 is common with fatty diets- homozygous can eat on western diet we have lots of fat, LDL bad cholesterol, would accumulate in bloodstream, and we would get heart disease, we want E3 e4- protect from Alzheimer's, 2% 2 copies of this allele and are very likely to succumb to Alzheimer's

gene therapy to deliver a blood clotting factor gene

have a clone gene insert rna version of normal allele into retrovirus or viral vector, works like adino virus, use hollowed out HIV virus let virus infect bone marrow cell that have been removed from the patient viral dna carrying the normal allele inserts into the chromosome- let virus infect but not the entire body, only bone marrow, can see where it is inserted into genetic material by sequencing either side of the therapeutic gene cannot insert into proto-oncogene

growing organs with stem cells

have a mold for stem cells , differentiate the right genes, grow more organs , can have spare parts from our own cells, no rejection with induced pluripotent stem cells

copies of gene used in 2 possible ways

have bacteria or other expression systems make protein coded by gene bacteria or yeast - can make human insulin, or study protein - expression systems insert copies of genes into organisms that need it - diabeteic humans could make own insulin- gene therapy

transgenic animals

have genomes that have been permanently altered through recombinant DNA technology - micro injection into the germ line only currently used for pharming, transgenic goat was engineered to produce human antithrombin in her milk ( approved to treat blood clots in USA and europe ) can produce spiker silk in milk of goats

papuans

have highest incidence of apoe e4 more than 50% little heart disease when they eat their traditional diet of sugar cane, taro, posums, and tree kangaroo western diet would have high risk of early heart attack

genetic inbreeding

health problems, closely related offspring tend to carry the same deleterious recessive gene to pass on

hexose accumulator and sucrose accumulator

hexose - helps with making a big tomato and sucrose makes a good tomato

HFR

high frequency, of recombination, - does not mean common 1/10000 insertions the F plasmid goes into cell and drags the host genes with it - recombination of chromosomal genes from bacteria into another insertion sequences in chromosome so plasmid can go into chromosome have the F plasmid incorporated into the chromosome Hfr mating with F cells rarely produce F+ because of how transfer occurs- takes too long, tube will break if successful- bacterial genes may be transferred from an Hfr cell to an F- cell during conjugation- crossing over can take place between the donated Hfr chromosome and the og chromosome conjugation produces a partial diploid can be converted into an F' cell

gonorrhea transformation

host genes in animal pathogens, bacteria that gives us gonorrhea, lots of animal genes in it- advantageous because proteins to mask from immune system

Pseduogenes

huge amount of pseudogenes more than any other mammal

chimp gene and positive selection

include many for micro-skeletal system, white blood cells and immunity semen coagulation proteins - to block rival sperm, produce sticky protein - caogulin , to seal off sperm so that other sperm cant go through it sperm competition drives evolution of larger testis 1 mya - bipedal , most apes, huge shoulders, long arms, bell shaped rib cage, adaptions in chimps- smaller thumbs - knuckle walker - our ancestors never knuckle walked , better immune system no HIV, no soft tissue cancer, more methylation

human and chimp differences

humans are pedomorphic ( neoteny) african apes human and chimp speciation occurred 6.3 mya 35 million human chimp SNP differences ( 1.06% differences ) ( 10,000 changed protein coding region genes and were subject to selection and mutations to regulatory regions) also 5 million indels ranging from 1bp to 15 kb, contribute to 90mb of divergent sequences (3.5%) of overall genome, mostly in regions that do not encode proteins 29% of orthologous proteins are identical - most proteins that differ do so by 1 or 2 amino acid replacements- can be a radical missense and can radically change the function of the protein can use monkey or mouse gene as an out-group to allow determination of whether sequence changes have occurred in the human or chimp lineages

where do allopolyploids come from?

hybridization between 2 species followed by chromosomes doubling

genetic screens

hypothesis free approach to biological processes-systematic collection of mutants gives unbiased view- allows surprises males eat food with mutagen ( EMS)- developing sperm and other cells each have different new mutations cross to wild type females, offspring each have different mutation, outcross offspring separately- making inbred lines of new mutations

human genome project

identify all the genes in human DNA determine the sequences of the 3 billion nucleotides that make up human dna store this information in publicly accessible data bases 40 years ago watson and other geneticist decided to change the way things are done, couldnt recruit people to do chromosome walking sold human genome idea to congress- have to be public so that no one can own it Vegner and Watson fought started the beginning of the democratization of biology was interested in 98.5% that is not genes new eyes to see what matters

melanin corpin gene

important gene in skin pigmentation , active gene working put melanin into skin african allele, negative selection, no non-synonymous mutations, short haplotype, european haplotype, positive selection, few non synonymous mutations, very long haplotype, many nucleotides bracketing the gene are conserved , broken, early humans up untill 10kya ate a lot of meat--> vitamin D , now need to make it in skin,

coalescence events

in a family tree of a finite population, it will occasionally happen that 2 or more different ancestors in the same generation share a common ancestor in the previous generations

natural selection

individuals with higher fitness survive and leave more offspring than individuals with lower fitness- their heritable traits increase in frequency in future generations fitness: individuals relative ability to survive ( viability) and transmit genes to next generation

iGEM/ accessible bio technology

international genetically engineered machine students work with biobricks, crispr , generate new bio organisms can use human genome project- public, can test ideas progress can be done by many people zagner: cutting and pasting genes, selling CRISPR, edit any genome- selling DIY gene editing kits biohacking: spaces for DIY possibility for bio terrorist

pericentric inversion

involces the centromere 3 human chromosomes differ from chimps by only pericentric inversion

DCH2S and GL13

involved in faces, why our faces are different than neanderthals

Hermann Joseph Muller

jewish, communist, geneticist nobel prize for mutation worked with soviet union and fought with stalin chief instigator of geneticist manifesto -1939 demand measure to improve genetic quality of the human race wanted equal opportunity - only genes would distinguish

copy number variations

large 1kb-1mb indels mean individual humans differ in size by about 9 million bases, but in some cases could be up to 250 million bases most humans differ by .5% CNV height , disease, sense, metabolism unrelated humans share 99.9% of dna sequence may occur within exons or non coding sequences 20% of differences in gene activity are due to CNV, shift in diets led to selection of cnv not well understand except when clear- such as chimps vs humans with amylase genes, started off with 2 amylase genes, duplication with unequal crossing over, more amylase you have, more amylase in saliva

1% of us have 2 copies of a small deletion in CCr5

largely immune to infection by the HIV virus evolved from black death - rare in africa- breeding population wiped out only children and elderly- then gene was selected for and now its common

polyploid plants

larger than their diploid counter parts , 1/3 all flowering plants are polyploidy, grass- polyploidy- good at it because no sex chromosome, self fertilization - good for polyploidy - double chromosomes- cell daughter of anther ( pollen) and ovules ( eggs) , both double , self fertilize- polyploid

haplogroup

last a very long time , mitochondria, y chromosome mtdna showed that cheddar man- stone age caveman and local school teacher share a common ancestor 9kya

american life from 1905-WWII

laws restricted immigration to " superior" people, restricted interracial marriages, led to involuntary sterilization ( negative eugenics ) , juge record office

paleogenetics

learned more with genomes than we have in past 150 years have 11 neanderthal genomes and denisovian genomes

transposons

less independent than plasmids, stuck in the genome, not defined- 42%- genome from retrovirus

comparing individual snps

likely differ by about 1/300-1300 bases, any 2 humans differ by 2-4 million snps out of a calculated 15 million snps, most probably no effect, snps we got in africa 35 million distinguishing us and chimps - we dont have many chimp genomes- dont know what variation chimp has,

"Chad" Sahelanthropus Tchadensis

lived 6-8 MYA oldest known hominid primitive ape features- small brain , brow ridges, small canine teeth comes from around the time we diverged from chimps last common ancestor of us and chimp right place , right time brain size of 350 cc hole in skull goes right underneath- bipedal quadrupedal- primitive condition chimps body has changed much more from CA than human has , are not 1/2 humans secondary quadrupedal - knuckle walker, chimp and gorilla bones suggest human s

selective pressure

look for regions of rapid change that indicate selective pressure- evolutionary change in genes is measured by the rate of nucleotides substitutions / number of substitutions taking place per nucleotides site

monosomy

loss of 1 homologous chromosome also fatal, exception x chromosomes cant do without an autosomal chromosomes- most genes present in 2 copies- batch of genes only producing 1/2 would throw the system out of balance

nullisomy

loss of both homologous chromosomes 22,000 genes- 46 chromosomes, cannot afford to loose genes, will impact every organ system in your body

selective sweep

loss of genetic variation following positive selection can identify recent human evolution by producing a map of positive selection long haplotypes at high frequency in populations indicate alleles that are so favorable that they spread rapidly through populations over last 5-10 k - allows no time for recombination- over this period high density populations, new diseases, and change of diet associated with agriculture have produced rapid evolution, allele common - long stretches of nucleotides and SNPs will be the same long haplotypes include genes for skin color, bone structure, metabolism of different foods and resistance of disease

spain and italy

lost approximately 1/5 of their population in the 17th century due to Corsair raids became slaves in africa 1200-1600 most slave trade went from africa--> europe people from southern europe slaves in northern africa european alleles in north africa- slave trade 4 million european slaves 17th century evened out- as may slaves going both ways

area 13

lost some enhancer for neural function, not all of our brain is bigger than chimps, area 13 is bigger in chimps area 13- suspicious, untrusting dogs and us have small area 13- childlike, social amygdala was the last developing part of the brain

latent infection with virus

lytic cycle genes are not being expressed, viruses are assembled in the nucleus of nerve cell when virus reactivates dna replicating of nerves- latent- stress-cortisol- nerves- viruses gets scared and goes into lytic cycle and want to leave

bacteriophage - 2 alternative life cycles

lytic phage: phage DNA digests host DNA , replicates and kills cell, virulent viruses , phage, sticks to host, digests, genes on viral dna, degrades dna, phage replicates , produces proteins that autoassemble around dna of the right size lysogenic: phage integrates into bacterial chromosome, becomes prophage, goes into chromosome , every time cell divides, it divides if anything bad happens to the cell the phage goes into the lytic cycle herpes

mutations to america

m45-m242-m3 traces a migration from centra asia to the americas within the past 20k years

p plasmid

made of pseudomonas aeruginosa - opportunistic pathogen go everywhere

edible vaccines

major killer of children in 3rd world countries - diarrhea get vaccines into 3rd world - with plants genes from human pathogen into bacteria that will infect a plant can grow and afford eaten uncooked so that it is not degraded problem: digestion of vaccine in intestinal tract potatoes - produce antigen ,need raw did bananas - resistant to cholera, typhoid, immunize by eating different antigens

zip code

major predictor of life span, depends where you are - environmental not genetic , to improve lives of americans - environment has bigger impact Ellis island- immigrants did really well for themselves by changing their environment ,

fusing techniques for recombinant dna into host cell

making eggs expensive , virus cant infect eggs micro inject provirus: uses ability to put its genetic material into yours injected provirus with GFP linked with another gene - linked gene present when green huntingtons gene - tried to find cures , monkeys went crazy and died with in a few months

black y chromosome

many african americans do not have african y chromosome because of slavery henry gates 44% african- ret is european and irish

inversion and translocation effects

may break a gene in 2 , bring genes under control of new regulation or cause position effects- methylation

meat products and transgenics

meat products are low in heart healthy omega 3- fatty acids pigs were transformed with a caenorhabolitis elegons ( worm ) gene encoding n-3 fatty acid de saturase that converts unhealthy omega 6 fatty acids into omega 3s has the same health benefits from eating pigs than from salmon - never sold

bacteria

metabolically gifted, sophisticated biochemistry- we rely on bacterial innovation- mitochondria-ATP cyanobacteria - photosynthesis

PEPCK-Cmus

mice can run 5-6 kilometers, speed of 20 meters per min for up to 6 hours, eat 60% more, remain fitter, live and breed longer- over expression of the gene for the enzyme phosphoenolypyruvate carboxykinase PEPCK-C stimulate efficient use of body fat for energy production michael phelps and usain bolt metabolically similar , utilize mainly fatty acids, produce very little lactic acid both have strange physiology, as both produce 1/2 the amount of lactic acid do not all carry PEPCK as it is more aggressive- such as genes for exceptionalism is linked with bipolar, pleiotropic

virus : replicating structure ( DNA/RNA) + protein coat

more independent than plasmids, need host to reproduce, capsid and protein wall

disease linked genes

more than 50% of the disease linked genes associated with psychiatric and neurological conditions, including autism , changes in genetic sequence and pattern of activation 12% of disease associated SNPs lie within protein coding area- 60% in function regions- promoters and enhancers

non disjunction during mitosis

mosaic expression in different cells of the body mutation of somatic cells do not affect gametes 1/2 turners syndrome has some xx- form clones- started off as all turner's but has high rate of spontaneous abortion- 50%- disadvantage- to 1x chromosome- non disjunction- some cells provide themselves with an extra x chromosome- out compete cells with 1X- patchwork- X0 ,XX homologous do not come together- both dragged to right- trisomy- 1 extra chromosome, can happen at any stage of your life

circular chromosome

most bacteria posses a single circular chromosome, bacteria contain plasmids,- small circular molecules of DNA

finding genes for enhancement

most genes have small affects, polygenic - lots of genes contributing identify key genes that make exceptional people exceptional

Hominid population and individual bottlenecks

most people are descended from founding populations 3000 generations ago- 60kya with a population size of less than 10k humanity was less than 10k - populations crashed we still have variation we had in africa 60ky is too short to generate complex adaptations weve had a lot of changes involving 1 or 2 genes

comparing species

most power that comes from the informational view of life derives from comparing species and individuals line up genomes and analyze similarities and differences look at changes that have happened since genomes shared a common ancestor identify conserved coding and non coding region

mammal polyploidy

mule is smarter than horse, stronger , disease resistant liger: 13ft bigger, more disease resistant , social, intelligent, sterile, mixture of chromosomes- need to do nondisjunction ( n=5 go to 2n=10 ) to double for homologs- cannot fertilize themselves

conserved sequences

multi species conserved sequences by comparing mammal, bird , and fish genomes identified 739,597 conserved non coding sequences of unknown function even in well studied genes many genomes from many divergence times 450 MYA- zebrafish- not preserved by chance - has functional significance lined up cystic fibrosis gene in fish , mammal, and bird, several regions conserved- no one knew did anything- have to be important

4 processes that change allelic frequency

mutation: origin of new genetic capabilities in populations by means of spontaneous heritable change in genes migration: movement of individuals among sub populations within a larger population random genetic drift: the random undirected change in allelic frequency that occur by chance in all populations but more in small ones natural and sexual selection: result in differing abilities of individuals to survive and reproduce in their environment

napolean and eugenics

napolean was a small man and wanted tall people in his army , many tall people died, 1.4 million in french military, reduced average height selecting for trait by killing enough people

cystic fibrosis gene therapy trials

nasal spray , contains virus with active gene to alleviate cystic fibrosis, virus without virulence genes, but working copy of cystic fibrosis pump - can put into asthma inhaler - cystic fibrosis patient takes puff every day , infect cells with virus and expresses pump monogenetic disease- single gene responsible for disease

hunting and genes

need to be social to recruit hominids, selection for more intelligent

plasmids

need to exist inside- uses its resources to replicate, some can be useful

chromosome walking

neighboring sequences are used to locate a gene of interest, a probe is a sequence of DNA that is labelled with a radioactive or fluorescent dye, a probe complementary to the end of clone A is used to find overlapping clone B a probe complementary to the end of clone B is used to find overlapping clone C continues until a probe complementary to the end of a clone has the gene of interest clone a is upstream of the gene of interest by making probes complementary to areas of overlap between cloned fragments in a genomic library, we can connect a gene of interest to a previously mapped , linked gene

DNA for ancient genomes

not from skulls or anything important , extracts from slivers of bones, from full range from where neanderthals were found , over 10K years to look at change over time and distance look at final touches at what made us human ancient genes that help modern humans - EPAS1 helped tibetans survive in low oxygen environments HYAL2- helps cells respond to ultraviolet radiation and is found in roughly 50% of East asians

bacterial death

not programmed to die like us, but you can kill it hard to define species as many species are all trading genes huge metaspecies 99% of all life

8 key variants in humans

not shared with neanderthals or denisovians that allow neurons to project further across the brain and connect with one another , changes in these genes are linked to schizophrenia - not there for that but they enable us to see ourselves in the world and how we interact, genes for politics are different between neanderthals and us , suggest neanderthals had more empathy than we do - enable them to be better hunters although neanderthal had bigger brain than we do does not mean it is more efficient , we have more connections between the different parts of our brain

interspeictic hybrids

often sterile because their chromosomes cannot pair during meiosis triploids are always sterile as you cannot have gametes with an equal number of chromosomes

trisomy

one extra chromosome 3 of some chromosomes lethal - except smaller with few genes - 13,18,21 small chromosomes non essential genes

autopolyploidy

one species, double chromosomes through non disjunction - gametes with same number of chromosomes as parent cell, together double chromosomes- new species - no longer compatible with parent species x = 2n=6 y= 2n=4 new species 2n=10

homosapiens evolutions

one species- many origins the idea that homo sapiens evolved from a single population in east africa has been undermined by discovery of human skulls across the continent - the huge variation in their features and dates suggest that our species was born from occasional mixing of many isolated populations new fossils suggest that our species emerged across africa many populations retained a diverse mix of traits in archaic and anatomically modern humans - 80-120kya brain case similar to modern human but posses brow ride and a projecting facial profile - when brain case witched to modern humans, still had archaic characteristics for a long time - archaic skulls are not gone forever

synthetic cell

operates off a chemically synthesized genome JCVI- syn 3.0 - operated off chemically synthesized chromosomes , genes made from scratch with nucleotides ordered to make a protein to a precise prescription venter-2010 florida based foundation for applied molecular evolution has added 2 based Z and P , proteins made with not naturally occurring amino acid

5 great apes

orangutan, 12-16 mya gorilla,6-8 mya human, 4-6 mya and chimps chimps and us- each others closest relation

origin of replication

ori - binds down dna polymerase needs this to replicate plasmid

triploids and us

our genomic imprinting , mom or dad turned off two copies of parents gene occur- is difference of gene products and genomic imbalance

advantages of genetic engineering

over conventional breeding- specificity- select genes, no shuffling of genes, can cross species barriers, cannot predict with natural selection

geography of lacrose intolerance

overlaps geography of cattle domestication lactose persistence is a derived trait by only 30% of humans ,baby produced lactase to break down lactose into glucose europeans and africans independently domesticated cows adult humans- waste of energy to produce lactase if you dont drink milk drank blood and ate cheese since the milk made their stomach hurt- independently get lactase genes that turned on for life- different mutations in the promoter europe- huge advantage, colonized all of europe, european languages travelled on the gene for lactose tolerance lactose SNP- ability to express lactase all the time- mutation in the promoter

origin of transfer

pass from cell- cell oriT- regulate plasmid transfer pilli synthesizing genes produce pilli to pull recipient bacteria/female - closer to donor - passes in 1 direction - can have many transfers at once plasmid

trisomy 13

patau sydrome (47+13) have 47 chromosomes , extra 13 on chromosomes 13 - genes for putting together hands and feet, where to put fingers, extra dosage- polydactyl common pain receptors- active at 6 months and can only live a couple weeks- should abortion be okay ?

agriculture issue

per capita food production is not keeping up with population growth 8 billion people by 2024, 810 million people will face chronic malnutrition and famine per capita population is rising faster than agriculture can still feed human population in theory as their is both obese people and starving people 40% earth land devoted to agriculture

RAG genes

picked up from viruses, immune system, placenta- trophoblast- viral viruses spread dna- 42% of our dna viral origin

biobricks

pieces of dna that have defines structure and function have been engineered to be interchangeable with one another for the sake of simple construction and modifications allow easy design and assembly of biological systems that can be incorporated into living things are exons- functional domains, autonomously folding proteins , mix and match different promoters , express during different circumstances, have different promoter and terminator but have the same restriction sites, use same set of enzymes and ligase to glue together create circuits- by joining- example of legos 10,000, many generators, come in filter paper and dissolve in water create organism- rust in drinking water, promoter turn on when there is iron, linked with RFP

Ti plasmid

plants have thick cell wall - hard to get DNA into them - two basic procedures bacteria: agrobacterium tumefaciens - cancers , is a soil bacterium, which is used to transfer a small segment of DNA into plant genome by the process known as transformation- dna of bacteria incorporate into DNA of plant, plant cell divide, bacterial cell divides too- plasmid - TI- can have tumor inducing plasmid, take out oncogenes but leave plasmid with ability to insert into the DNA of the plant engineer plasmid- no onco, poly linker sites , gene of interest, put back into bacteria- back into plant cell - plant genome cant cause cancer anymore, uses restriction enzyme and ligase method: gene gun, blast of steam , shoot golden particles with dna - called pellets, around edges , cells with pellets in nucleus can release dna gold- soft and non reactive

mammalian expression vector

plasmid with promoter- make protein from gene- if you want gene expressed in every cell - actin - can be therapeutic protein - protein for medicine bacteria expression system with control elements for bacteria gene origin of replication and repressor and operator repressor can bind to ribosome binding site- shine delagarno sequence selection of restriction sites- poly linker- choice of several different restriction sites transcription terminator sequence- need to end transcription so it doesnt keep going around selectable marker want to retrieve protein - put in casein promoter- inducible promoter so that the protein is expressed in milk - expressed only in mammary glands promoter upstream of dna insert

polyploidy in humans

polyploidy related to death in humans is unknown most organisms, polyploidy is normal in appearance than aneuploid, as 1 extra chromosomes disrupts genetic imbalance more than entire set of chromosomes common in asexual plants and animals that develop from unfertilized egg

FOXP2

positive selection in humans pleiotropic transcriptional activator , effecting speech old gene for motor skills given a new job- present in drosophila, pleiotropic, taken gene that moves our mouth coopted to put words together , new alternative promoters, express in brain, missing in chimps mice without FOXP2 or expressing the human variant- squeak differently human foxp2 turns on 116 more genes than the chimp version in human brain cells coding sequence the same in neanderthals and denisovians - and us paul boca- patient could only say tan, lesion in broca's area of the brain wernick's area: words broca's are: putting words together FOXP2: grammar , implicated in capacity for language, dn/ds= 2/0, change selected for in apes , chimps , gorillas : 0/7

P4 medicine

predictive, preventive, personalized, participatory Leroy Hood 21st century medicine, should be born, then genome is done, knowledge which medicines work , monitor , and obtain stem cell from umbilical cord

controversy of stem cells

president bush II, developing stem cells from fetuses, fertility clinic- religious objections

keratin

produce hair shafts, only mammal that has continuous growing hair, hominids had really long hair - sexual selection theory, out genes for hair massively rewritten

why is aneuploidy bad?

produces serious developmental affects by altering the dosage of some genes, disrupts concentrations of gene products

katie pollard

programmed , ran computer code that identified human sequences that changed the most compared to orthologs in chimp, mouse, and others- found 721 HAR looks at the 35 million SNPs to see whats important, bits of our genome that is radically different than the chimps and conserved in other mammals - hypothesis - unique DNA in us , lots of mutations, rapid evolution

egg laying ancestors

pseudogenes- descended from common ancestor monotreme- platypus have working yolk gene compare to yolk genes of chicken very distantly related to us when mammals first evolved - mammal like reptile

human hybrids

races will have different recessives sickle cell anemia recessive in Africa and Sweden would have recessive cystic fibrosis

specialized transduction

recombination between viral chromosome and the host chromosome produces a viral chromosome containing a piece of bacterial DNA plasmid into host, comes of out host with information- F' prophage - viral dna in bacterial cell- mistake - viral dna not completely excised - chunk of host chromosome - specialized- only dna adjacent to virus gets pick up prophage is incorrectly excised from bacterial chromosome

many hominid populations

red deer cave fossils dated to 11.5 years ago had many hominid populations , had hobbits on island of florence- possible offshoot of homo erectus diverse hominids but we were last ones- with complex web of interbreeding are we different species, our evolution - 31k snps not found in chimps, neanderthals, and denisovians, 96 protein changes and 3000 changes in regulatory regions

Human Accelerated Regions (HARs)

regions that have been frozen throughout human evolution - indicating selective pressure to maintain them but where there is a sudden burst of change in the human lineage majority are in gene regulation , sitting in front of genes - when and where the gene is switched on/off during embryological development , transcriptional activators, produce protein that turns on a cascade of genes so the little DNA has a major impact when affecting TA developmental genes-blocking development and duplicated genes( 1 gene maintain functions and one gene gets new function) short 100-200 bp mostly non- coding 4% protein more than 1/2 HARs up regulate genes involved in brain development- changes in these regions could have altered the human brain by influencing the activity of whole networks of genes 721

consanguinity

relations mate together more than 1 billion people live in societies where consanguinity is common born in Bradford project, cousins-cousin, shows recessive inherited defects studying Pakistan population- consangious children do better with more resources

stem cells

relatively unspecialized cells that can reproduce indefinitely ( telomerase turned on ) and under certain conditions - differentiate into one or more cell types another cell produce growth factor- gets cell to differentiate- any cell in potential of that stem cell

mouse cas9

replace gene from blind mice introduced cas9 can cut out bad gene and deleting gene - knock out mice- see impact each gene has- see phenotype

p and f plasmids

replicate autonomously to integrate into bacteria chromosome if they have direct repeats and insertion sequences

electrophoresis

restricted dna fragments are separated, separate based on size and can be combined using ligase small dna travels faster- what does each dna do- genetic screens dna samples containing fragments of different sizes are placed in wells of agarose an electrical current is passed through the gel all dna fragments move toward the positive pole, small fragments migrate faster than large fragments dye specific for nucleic acids is added to the gel dna fragments appear as bands

robertsonian translocation

resulted in humans having 23 pairs of chromosomes as cf.24 in apes the short arm of 1 acrocentric chromosome is exchanged with with the long arm of another creates large metacentric chromosome and a fragment that fails to segregate and is lost human chromosome 2 contains a robertsonian translocation that is not present in chimps

san people

separated from the rest of homo sapiens 100kya, most human variety are in the san people if wiped out mitochondrial eve would be more recent see variation in us oblong skull, high cheek bones, founds in africa and europoean variaiton and diversity of skin types closest line to homo sapiens 200k people before we diversified into races

dog variation

show simple mutation with major effects created in last 15k years have huge size different because of 3 genes , 1 major growth factor gene

sticky ends

single stand overhangs caused by staggered cut of inverted repeats- fragments of DNA cut by the same enzyme can be joined together since they have complimentary ends can also have blunt ends

eugenic advocates

sir charles galton darwin- result of galton and darwin inbreeding darwin equation, leading english advocate of eugenics harry laughlin ( sterilization laws ) and charles davenport- american eugenists, first country to introduce eugenic laws davenport- associated mental and physical defects between inbreeding of poor white people, introduced racial aspect, interested in family evaluation ( would go back in history of the family as far as he could ) , created huge record office of database of genetic information- inventory of the blood of the community , still one of the largest collections of genetic info we have mary watts and florence sherbon : colleagues of laughling and davenport, eugenic exhibit and state fairs karl pearson-galton student , developed chi squared test TDR-president of america, the great race of northern europeans were betraying themselves by not having enough children H.G wells- author, socialist and eugenicist, children can no longer be a private concern colleges and professors taught eugenics, in textbooks black leaders - also eugenist, wanted to create a black population asia- also eugenicist, still are in china and japan

stem cells

skin cells taken from patient with genetic defect skin cells -- > stem cells HAC with healthy gene inserted into stem cell stem cells with HAC transplanted into patient to correct genetic defect

skin fibroblast cell --> iPSC

skin fibroblast cell- 4 master regulator genes , 4 transcriptional activators , were introduced, using the retroviral cloning vector--> induced pluripotent stem cell

human civilization hurting natural selection

societies protect under privileged and weak brains are shrinking- greatest evolutionary biologists believed that civilization was ruining the human species, degernations of human species because we are all breeding - selfish gene theory in stone age if there was bad eyesight - cannot pass on genes crabtree- many genes involved in intelligence, a lot of dna for mutations to occur, genes for intelligence are being mutated and mutations are accumulating as it is not dis advantageous anymore ( with the development of agriculture, urbanization weakened the power of selection ) issue of past 20-30 thousand years, our brains have shrunk my 250 ccs intellectual abilities were highly selected for - hundreds of thousand never made it- weeded out because of mistakes in stone ago 100 years ago - infant mortality 30% now less than 1%

700 regions of strong selection

some populations that adapt to different environments and cultural changes last 8000 years , our genome has 700 regions for strong selection - not all over the world because there was different selective pressures high altitude in tibet- for several thousand years people died, people who could adapt had mutations which became fixation 100% of the people now have that mutation, selective sweep has been complete , bigger eyes at higher altitude

hybridization with polyploidy species

species x and y= 6 chromosomes and 4 chromosome - hybrid, mammals can do this- horses and donkeys will give mules- sterile-unique chromosome with no homologs to be fertile - has to non disjunction - chromosome doubles to produce homolog for itself ( n=5, 2n=10) - early mitotic event- pollen and egg daughters with double chromosome- normal meiosis - fertile hybrid cell with 2n=10, two n=5 cells that can now fertilize into a fertile hybrid

triploid forming

sperm goes through egg- mucus hardens - sometimes 2 sperm get in , generally triploid- disaster- very rarely triploid infant born- mosaic - have to have diploid just to get to being born

mosaic patchwork of trisomy

studied in chromosome 8 - cannot be born with trisomy 8 , non-disjunction, during mitosis some cells have three chromosome 8s, big chromosome but not many essential genes- only chromosome that doesn't genomic imprint , gene from mom and dad function, section- rapidly mutating genes evolved how brain is put together and compartmentalized, structure and function- cells with trisomy 8- continue to divide - in different organs and and tissues - furrows in feet- head put together with lots of trisomy 8- brains with no separate sections and no emotions

homo erectus

spread across the world, first out of Africa, interbred with Neanderthals and denisovians - hard to distinguish different species , 40kya interbreeding - neanderthals account for 2% of the genes in non-africans - we each carry different parts of the neanderthal genome 1/2 million years - used fire to harden spears, changed bodies, lost 3 feet of gut, narrow hips, legs close together, could run far, early homo erectus had long arms to climb trees had 70 different races, first hominid that you could see whites of eyes- chimps have no whites so you cant see where it is looking

evidence based medicine

statistical approach using the rule of large numbers 60%- most drugs are not effective or only partially effective 100,000 deaths 2 million hospitalization 100 billion costs for healthcare effects of not taking in account genome and biochemistry of patient reactive medical care: trial and error, medicine known to treat disease might not treat that person

competition of stem cells

stem cell lives on agar plates, can have selection on stem cells as they compete with one another, can turn into cancer type - stem and cancer very similar cells

stem cell from mouse example

stem cells from mouse's gum - pluripotent- able to craft skin with multiple layers including hair, and sweat glands when placed in a mouse with a suppressed immune system , grew well--> first time artificial skin could have hair follicles and endocrine glands, which play an important role in regulation - use GFP

Eugenics Movement

sterilization of mental deficient, believed social worth= genetics worth if bad genes were the problem then careful breeding was the solution issue: most of us carry harmful recessives, cannot weed out recessives without killing people, selection operates on traits not alleles

issues with our backbone

strange arrangement, back issues , 200kya evolution to perfect backs, now selection wont happen on our back as it doesn't affect sexual selection

example of stem cells

take skin cells- give it 4 master regulators and 4 transcriptional activators, backtrack to turn skill cell in induced pluripotent stem cell use retrovirus- turn on and put master regulators in the cell , strip the methyl groups, genes become active, can now use as a pluripotent stem cell for any type of skin cell - need a signal, growth factor, there is a signal transduction to up regulate for that tissues master regulator have a heart attack- heart cells dead- put stem cells in to repair damage, with the master regulator of cardiac cell- HandIII- will turn on subset of genes that are the proteins of cardiac cells lose thigh muscle- stem cells produce skeletal muscle MyoD- new tools to convert into 300 tissues in our body

why chromosome walking was an issue

takes a long time and money could not recruit people to do it - now we use human genome

The Hype Cycle

tend to over estimate the effect of technology in the short run and underestimate the effect in the long run 1980s- gene therapy, replace with working gene ,thousand different studies, disaster, man who had rare genetic disease died in a trial, was working with adino virus- injected genetic material into nuclei, and died from immune response, funding lost, trials cancelled last 10 years:, recovered , more cautious 10 year rule- over estimate what we can do in 5 years and under estimate what we can do in 10 years

red vizcach rat

tetraploid mammals, different species- allotetraploid best genes of each species to survive in harsh conditions- down to genomic imprinting- takes bet of 2 species to survive- methylate others

conjugation process

the F factor is transferred during conjugation between F+ and F- cell F+ is the donor bacteria and F- is the recipient bacteria during conjugation a cytoplasmic connection forms - protein tube forming between - proteins to make pilli in the genes of the plasmid oriT- one strand of the F factor is nicked at an origin of transfer and separates replication takes place on the F- factor- replacing the nicked strand the 5' end of the nicked strand passes into the recipient cell where the single strand is replicated- produces a circular double stranded copy of the F plasmid- F- cell now becomes F+

upright position

the laetolic footprints more than 3.5 MYA confirm the upright position evolved in early human history a. afarensis - ancestor of first hominids human anteccesor- may be CA of humans and neanderthals homo erectus- pivotal 1 mya - bipedal , most apes, huge shoulders, long arms, bell shaped rib cage, adaptions in chimps- smaller thumbs - knuckle walker - our ancestors never knuckle walked - chimps and gorillas evolved trait separately

robertsonian

theory all metacentric chromosomes derived from acrocentric by a translocation event exchange short arm for long air- dna repair- lose a bit- fragment - around centromere is highly condensed anyway- might not loose any genes we can no longer mater with chimps - 24 chromosomes pairs, chromosome 2 in us and their acrocentric line up

somatic gene therapy

therapeutic genes usually delivered by virus that disease caused by loss of function mutations ( blindness caused by defect in RPE65 gene) or provide nerve growth factor in Alzheimer patients, blood vessel growth factors for heart disease, often take patients stem cell outside of body, infect with disarmed virus, retrovirus, carrying functional copy of gene and then return to cell cancer risk if virus mutates proto oncogene

when are aneuploids produced?

through non disjunction in meiosis I, II, or mitosis

Nazi and eugenics

took up eugenic ideas of galton's "master race" to validate producing one, took up inferiority up other races and sterilization laws, combined with anti- semitism and concepts of race to justify sterilizing and killing people with disabilities eugenics came crumbling down with nazis - their final solution was not only jews and poles but all eastern europe fro living space for the germans positive eugenics: recruited 10000 women from german empire to mate with officers

cave in denisovia , siberia

tools for jewelry mtdna- novel species more technologically advanced than H. sapiens or neanderthals

genetic engineering

transfer of a gene from one organism to another facilitates biotechnology-techniques for using the properties of living things to make products or provide services- basis of agriculture-1st industry 6 kya- used yeast to make bread-,ferment honey, make alcohol cutting and pasting pre - existing dna, joining together dna

how to put recombinant dna in host cell without destroying it

transformation e.coli- less than 15 kb transduction - virus 25 kb can buy viral capsid proteins - mix dna of right size, proteins auto assemble around dna can infect mammal micro injection: mate mice , short period of time before nuclei fuse- pronuclei , use suction , grab fertilized egg- large nuclei sperm, use needle 100 copies of trans gene, may insert or could destroy nuclei but sometimes it may work - let cell divide and insert cells into embryos - insert into pseudopregnant female ( zapped male testicles with radiation - sterile and mate with female ) which offspring has gene of interest: take blood samples , run in gel, find gene find heterozygotes mouse-1 nuclei carried gene- mate mice together - homozygous gene of interest

3 mechanisms of horizontal gene transfer

transformation: dna from the dead conjugation: sex pilli transduction: virus transfer

GMO

transforming agriculture, plants already engineered, wild plants are not as large- can also make new varieties of plants- blast with radiation - select for that - grow the biggest- random genetic engineering - more specific carrots were originally purple- orange because of protestants can engineer wheat plant to be resistant to plant pathogen blue roses - took genes from petunia can have improved nutritional content- cereals engineered with yeast protein to provide essential amino acids you cannot make and need in your diet ( corn and beans ) - tryptophan, methionine, valine, threonine, phenylalanine, leucine, isoleucine, lysine took gene from yeast- isoleucine and lysine and put it into corn cereal with all the amino acids you need

familial down syndrome

trisomy 21 can be inherited translocation 1 chromosomes 21- other on chromosomes 14 , non- reciprocal translocation - diploid but chromosome 21 is stuck on 14 produces 2 kinds of eggs- egg with chromosomes 14 + 21 egg with 21 on top of 14 + 21 sperm- 1 copy 21 and 14, sperm hits egg with 2 chromosome 21s- 3 copies of 21- down syndrome

conjugation

two bacteria next to each other share information

whole genome sequencing of family of 4

unaffected parents/ gene - children with craniofacial malformations and lung disease- from consanguinity in Utah- recessive no genes had been identified the genome sequences of a family permit one to use the principles of mendelian genetics to determine intergenerational mutation rate- 35 mutations per child identify candidate genes for simple mendelian genes- 7 pr 8 genes - look at what genes do identify all genes that are homozygous in children that are heterozygous in parents and test these in mice

olfaction genes

under positive selection in humans while other olfaction genes are losing function 50% ours broken, 33% broken in chimps but we can smell cooked meat

alpha tectorin

under positive selection in humans, ear protein involved in high frequency for speech

AMY1

under positive selection in humans, encodes salivary amylase , humans have large number of the AMY1 genes , allowing digestion of starch farming population has more amylase genes than hunting population varies between human cultures and population- people with high starch diets, have extra gene copies of amylase compared to hunter/gatherers, increasing concentration of salivary amylase such as chimps vs humans with amylase genes, started off with 2 amylase genes, duplication with unequal crossing over, more amylase you have, more amylase in saliva agriculture the longest, accessing starch the longest, most amylase genes- with a high starch diet= more amylase copy number hadza: had agriculture for a long time , many amylase gene independently people who had high starch diet : unequal crossing over, extra amylase genes have been selected for

enzymes for amino acid catabolism

under positive selection in humans, rapidly rewritten in us compared to chimpanzee, we eat more meat, meat= amino acid, need to extract nutrients for amino acids so our brain is more efficient

human genetics

understanding individuality enumerate all variation and correlate with bad traits then good health and good traits sequence genomes of 20 people who lived over 110 years to identify protective alleles, many have protective set of genes that override genes associated with disease and aging- found people who are homozygote for cf gene but dont have it because of protected gene for longevity 5 biochemical pathways affected, affect insulin IGF1 pathway have high serotin , low cortisol

xenotransplantation and crispr

use CRISPR to edit genes and convert pig sequences to human sequences, helps with xenotransplantation, use animal organs for people in need of a transplant had previously failed because of differences in the genome that caused organ rejection and blood clots have a shortage of organs - tried using pigs but there was a huge immune rejection to replace large chunks of genome- dna synthesis smaller alterations- crispr issue now: pig transposons and retrotransposons are not the same

large factory of oil from algae

use oil as storage as we use glycogen , algae farms, engineered, 20000 gal of algae with extra genes to produce more oil and pump to harvest yellow algae- sun can reach everywhere- human and virus genes into the algae, produce many carbohydrates and proteins possible get rid of agriculture, we know vitamins and ingredients in each produce- algae produce same in 2-3% of land mass opposed to 40% used today craig venter

neanderthal and denisovans relation

very closely related, their common ancestor split off from ancestors of modern humans about 500kya neanderthals and denisovians split about 300kya represent the last divergent branch of the human evolutionary bush comparing genomes allow us to find genetic differences that allow us to conquer the world while neanderthals died out 25kya share epigenetic methylation pattern when humans vary

transduction

virus carries genes from one bacteria to another

restriction fragment polymorphisms to map genome

use restriction enzymes that cut at a specific site EcoR1- cuts GAATC only SNPs- take away or provide with new restriction sites take dna from people - 10,000 frame, 8 nucleotides difference, cut stretch with EcoR1, find polymorphism different size fragments when run on a gel - restriction fragment length polymorphisms - distinguishes differences in size- find a banding pattern, - which can be associated with a particular disease- SNP can be close enough to the disease causing gene that it was not separated during crossing over- within 1 million bp cystic fibrosis - fragment they found that marked people was 1 million bp away - can walk way to gene- once a fragment pattern is found that is associated with the disease clone A- have RFLP markers take end of clone A- attach P32- end of clone B add P32 - next piece of dna 1500 bp at a time to walk to gene of interest - that causes phenotype- will eventually find issues - missing CTT= cystic fibrosis, walked until found sequence always missing in people with cystic fibrosis--> then PCR amplify Dna to find if missing - run the gene, sequence resembles all other sequences that are pumps- now know absent gene of interest- help overcome affects of gene

evolutions to modify our environment

used out brain and opposable thumbs to modify our environments- gained genetic adaptions to fully exploit the new environments we have created if in artic we want to use culture and animals instead of genetic changes

gene therapy insulin

used to be from cattle, differ by 2 amino acids , people developed an allergic response took genes encoding human insulin- put into plasmids, express in E.coli- did not go well- bacteria do not fold proteins in the same way- do not add glyco or add carbohydrate the same way we can use yeast - insulin by yeast with human genes

molecular techniques

used to isolate, recombine, and amplify genes

human population genetics

uses mtDNA and y chromosome YDNA y chromosome is always from dad, only have crossing over at ends- millions of bp of mostly junk dna that provide a historical record y - single african man 200-270kya y chromosome adam mitochondrial dna cannot cross over, 1600 bp passing through generations, in past there was fewer mutations, time with 1 mitochondria sequence - mitochondria eve, many human beings at this time but they did not leave mitochondria to future generations women in africa 150-200kya autosomal would have crossing over can trace both back to 1 person - hitler could have changed identity of mitochondria eve - eliminated variants haplogroups - each unique combination of nucleotides represent a different y and mitochondria haplogroup - last a long time trace back until you ran out of variation, fewer and fewer bp changes,

gene therapy

using virus and its ability to inject genetical material into genome- replace faulty genes induce gene , recessive disorder, give working copy not as successful as it could , technology could not back it up, virus as treatment - difficult to work with

more than 1 x chromosome

usually fine because all but 1 is inactivated, autosomal aneuploid have no mechanism for dosage compensation

plants as factories

vaccines and bio degradable plastic

genetic recombinations

vertical gene transfer- occurs during reproduction between generations of cells horizontal gene transfer: the transfer of genes between cells of the same generations

denisovians

very big, possibly bigger than heidelbergensis 260 amino acid substitutions compared to us - CNTNAP2 - language disorders, language differences, probably had a long thin tongue lived 40kya, widespread through asia, diverged from neanderthals 5% of the dna in people in Papa new guinea derive from denisovians africans have no denisovians dna

virus as gene banks

virus carry large loads of DNA they dont use - transfer dna to bacteria during infections - help with evolution of microbes metagenome- genome of environment, most dna- viral , found genes to make flagella, virus does not use, transfer genes to another bacteria

spacer

virus invades the cell, cas proteins bind to the viral dna and cut a chunk- chunk of viral DNA is carried back to the bacterial cell's genome , where it is inserted, becomes spacer in crispr dna goes into genome record - and daughter cells know how to fight the virus

biosilk

want strongest silk - the one they use to hang with - put into goat

sexually mature baby chimp

we are sexually mature baby chimps magnum- directly under skull just like us - adaptation to hang on to mothers fur - face flat, room for brain , small teeth, less suspicious, playful, retain box like skull, fewer allometric changes- our evolution is breaking developmental genes so that we never get to adult ape stage our genome is a wreckage ground of adult ape genes adult chimp changes a lot from infant than we do , more allometric changes

dinosaurs

we have no dinosaur dna , change sequence of chicken has dormant genes for teeth, claws ,snout go to archaeopteyrx , first bird hoaztin has claws on its wings

weuse and transformation systems

with e.coli mass produced transgenic proteins dna isolated genes- mass produce gene - put in E.coli transform e.coli, resistant to transformation naturally- make it competent by damaging the membrane with calcium and cold- recombinant dna/ plasmids, put in with bacteria and force it to take it in modern electrophlocation- bacteria and dna- zap of electricity, dna- neg, fast to positive into bacteria

personalized genome

would tell you exact variants you have people from coastal regions- salt gene broken, can eat salt without high blood pressure disease alleles were beneficial at one time not there to give us ashma, diabetes

synthetic biology

writing and programming new DNA- create genetic machines creation of a bacterial cell controlled by a chemically synthesized genome two main goals : create genetic machines and insight starts from scratch make living things to understand them can digitize biology by decoding the genome, can have digital dna and experiment on computer make synthetic dna and put into yeast, assemble genome using dna repair system 2010- chemically synthesized a genome can synthesize novel genes that produce primary sequences that fold up to gene properties never seen can replace recombinant DNA technology

y chromosome adam

y chromosome is always from dad, only have crossing over at ends- millions of bp of mostly junk dna that provide a historical record y - single african man 200-270kya y chromosome adam mitochondrial dna cannot cross over, 1600 bp passing through generations, in past there was fewer mutations most people coalescence to someone who lived 170kya - a few hundred people in africa have an older archaic y chromosome y chromosome of Neanderthal coalescence to 550 kya more information as the y chromosome has more dna to mutate -15 million mitochondria 1500 bp - and functional which limits mutation india - mitochondria is not delineated indicates women can cross caste system