Genes and populations
What does neanderthal DNA sequencing tell us?
3 mitochondrial DNA sequences have been analysed and show they are distinct from modern humans. It also shows they are no more like european humans than other modern humans. MtDNA provides no evidence that Neanderthals and modern humans interbred
What are Drosophila melanogasters?
A Drosophila melanogaster is a fruit fly and is used in genetic studies because they breed and mature quickly. They have a rapid generation time and are easy to rear
What are pedigrees?
A chart or "family tree" that tracks which members of a family have a particular trait. - empty square is male unaffected - filled square is male affected - empty circle is female unaffected - filled circle is female affected - empty diamond is unknown gender unaffected - square with a dot is a carrier - square with a cross through it is dead - line between two is marriage - double line is incestuous marriage
What is recombination?
Also called genetic recombination, is the process that introduces genetic diversity into the gametes during meiosis. There are 2 processes that make up recombination: independent assortment and crossing over. The enzyme nicks one strand of DNA at a homologous sequence. Recombination enzyme inserts the cut strand into second molecule which is nicked in the process. Ligase anneals nicked ends in new combinations and then the molecules resolve into recombinants
What is balancing selection?
Another form of natural selection that can happen when heterozygotes are fitter than homozygotes
How do pea plants cross-pollinate?
Anthers are removed before they shed pollen and then pollen is transferred from plant to plant
What is a threshold trait?
Appears like a discontinuous trait but is caused by a continuous distribution (caused by a variety of genes). The distribution is called liability.
What happened to the frequency of melanic moths after the clean air acts?
As pollution declines, the melanic form is no longer cryptic to birds and so they lose their fitness advantage
How have humans adapted to climate?
As the humans moved out of Africa they experienced new environments. Melanin is the most important pigment affecting skin colour. Eumelanin synthesis associated with black/brown pigments. Phaemelanin synthesisi is associated with red/yellow pigments. The negative effect of UV can cause sunburn and damage to sweat glands, eventually leading to skin and eye cancers. It can also cause nutrient photodegradation of flavin, carotenoids and dolate (neural tube defects). In Africa dark skin is necessary for protection from UV but little vitamin D is produced. In europe light skin is necessary for vitamin D production especially as high grain diet is vitamin D poor and UV levels are lower.
How do you asses goodness of fit?
Associated with the x^2 value is a number called the degrees of freedom which is the no. genotypes - no. parameters estimated = 1. If the degrees of freedom = 1 then the null is rejected.
What are the fossil records for the history of humans?
Australopithecines are ancestors to hominids with large faces and smaller brains, they arose almost 4.2 million years ago. There are also Genus homo. Homo erectus arrived around 2.5 million years ago in africa, followed by heidebergensis then neanderthalensis. Anatomically modern humans arrived in ethiopia around 154-160 thousand years ago
What are the five mendelian patterns?
Autosomal dominant Autosomal recessive X-linked recessive X-linked dominant Y-linked
When was the 6th extinction?
Believed to happening now due to human activities; habitat destruction, fragmentation, poaching and hunting
How do you estimate allele frequencies
Collect a sample of N Denote the frequency of A1 by p and A2 by q The total number of alleles is 2N Every A1A1 has two A1 alleles and every A1A2 has one A1 allele Frequency of A1 is *p = number of A1/2N* Frequency of A2 is *q = 1 - p*
What was mendels first cross?
Crossed two true breeding plants together (smooth and wrinkled) outcome: all f1 had the same phenotype. He found a 3:1 ration in his f2. The data meant that alternate versions of a gene cause variation due to alleles. An organism must inherit two alleles from each parent which can be dominant or recessive. These alleles segregate during gamete production
How can you apply hardy weinberg?
Cystic fibrosis is an autosomal recessive disease (the normal allele p and the disease allele q). In the UK cystic fibrosis affects about 1/2000 newborns
How did humans adapt to disease?
Cystic fibrosis. It is the most common autosomal recessive disease in europeans and eveidence suggests that heterozygotes for it are resistant to cholera/typhoid. The delta508 mutation is 10,000 to 50,000 years old and the geographical distribution suggests european origin. Conclusion may have reached high frequency in europe because heterozygotes are resistant to infectious disease
What is X-linked dominant?
Each cell of the females have one X that is randomly inactivated. This can affect either sex and the child of an affected female and has 50% chance of being affected. A female children of affected males are affected but no male children of affected males are affected. This does not pass on an X chromosome to male offspring but does pass it on to their female offspring. (rickets)
What are captive breeding programs?
Endangered species with a relatively small population are often reared in captivity. Some inbreeding is unavoidable. Californian condor are in these programs but a lethal recessive allele has reached high frequency. Homozygous birds suffer from chondrodystrophic dwarfism and may die at hatching. The breeding programs have to ensure heterozygous carriers do not mate so a quarter of the the offspring will die
How can you test departures?
Estimate the allele frequencies. Calculate the expected genotype frequencies under the HWE Calculate the expected genotype counts in the sample Calculate the chi-squared statistic
What is Y-linked?
Every son with affected dad is affected but females aren't at all, they can't even be carriers
What is gene mapping in finland?
Finland is geographically remote and has a small founder population and several bottlenecks. They use the uralic language which is a barrier to immigration and admixture. Some genetic diseases are virtually absent (cystic fibrosis). Others are at quite high frequencies are well characterised. They have good genealogical records and carriers of disease all have common ancestry which increases chance of detecting genes responsible
What is positive selection?
For a gene with two alleles A1 and A2. Allele 1 is under positive selection if it offers a selective advantage over allele 2. As a result, 1 is increasing in frequency and replacing 2. The increase in frequency of the melanic moth form in polluted areas was driven by positive selection.
What do you expect vs what was observed from tracking two characters at the same time?
For example; yellow, round (YyRr) x green, wrinkled (yyrr)q. The expected F2 ration is 3:1 yellow : green, 3:1 round : wrinkled. What mendel observed was 9:3:3:1 of round yellow : round green : wrinkled yellow : wrinkled green
How can you map diseased genes?
Genetic drift is the random loss of genetic variation which occurs quickest in small populations. The loss of genetic variation appears to affect extinction risk. Inbreeding is more likely in small populations and is measured by the inbreeding coefficient (f). Inbreeding depression is the reduction of fitness due to inbreeding. Conservation genetics aims to reduce the loss of genetic variation and avoid inbreeding. Isolated human populations have high incidence of some genetic diseases so they can be used to map disease genes.
What was Morgans experiment?
He mixed purple (r) with red (R) eyes and vestigial (v) and normal (V) wings. He crossed RrVv x rrvv expecting equal numbers of all 4 possible outcomes. However it wasn't equal so the two genes do not assort independently and they must be linked
What happens when uou increase genetic variance?
Heritability gets bigger
Who is Morgan and how is he related to chromosomes?
In 1903 it was suggested that factors (genes) must lie on chromosomes. In 1909-10 there was the first proof from the fly room with white eye mutants
How can you verify Mendels first law?
In homozygotes an individual has two copies of the same allele, and heterozygotes have two different alleles. Using a test cross you can cross a heterozygote with a homozygote for the recessive allele. You will find an equal number of recessive and dominant phenotypes
What are the consequences of inbreeding?
Inbred progeny have higher f values than outcrossed progeny. If the alleles at a locus are identical by descent the locus must be homozygous. Higher frequencies of homozygotes in inbred populations reveal recessive deleterious alleles and are less likely to benefit from heterozygote advantage. Inbred progeny often suffer from inbreeding depression.
What effect did agriculture have on humans?
It changed the lifestyle of hunter-gatherer to living in settlements and drove the expansion of human population size. One consequence was the increased risk of infectious disease. By making phylogenetic trees it is possible to determine when and where domestication happened. All genotypes were in one clade, domesticated in the near east and had just one domestication.
How does natural selection occur in sickle cell anaemia?
It is a recessive disorder caused by a mutation in the beta-haemoglobin gene S (disease) is recessive to A (normal form). AA means no anaemia, AS usually healthy, and SS which is severe anaemia. The evidence is the extensive overlap of the geographical distribution of sickle-cell anaemia and that of malaria. AS red blood cells do not normally sickle, but when they do they become infected with plasmodium flaciparum, the cell is destroyed and the parasite killed in the process. The S allele is maintained at high frequencies
Is Hardy-Weinberg useful?
It provided a description of how genetic variation is maintained as frequencies are constant over time and shows how blending inheritance does not happen. However departures from HWE mean that some assumptions are not met
How does 'time to most recent common ancestor' work best?
It works best with non-recombining molecules such as mitochondrial DNA which is found in both sexes. It is maternally inherited, small molecules and has a high mutation rate. It also works with Y chromosome DNA which is found in males only, paternally inherited only and does not recombine with X chromosome.
What was a badly designed recovery program?
Koalas were hunted for fur and for sport and in the 1930's they were gone from S. Aus and almost absent in Victoria. 2-3 surviving individuals founded a population on french island and reached carrying capacity. 18 adults and offspring were used to populate kangaroo island and now theres 10,000 animals across australia
How have humans adapted to diet?
Lactase is the enzyme that digests lactose and in most populations the ability to digest lactose diminishes after weaning, and can ead to consumption of milk causing abdominal. In some populations lactase persistence lasts into adulthood such as in N.E and parts of C.A. Lactase persistence is an adaptation inherited as an autosomal dominant mendelian trait. The persistence allele is dominant to lactose intolerance allele.
What is X-linked recessive?
Males only have 1 X-chromosome and the females need both X's to have the disease as its recessive. Males cannot be carriers and if they have the gene they will always express it. Females are only affected if father and mother are affected/carriers. (duchenne muscular dystrophy, red-green colour blindness, haemophilia)
Why did Mendel use pea plants?
Mendel used pea plants because of their: -short generation time -large # of offspring -controlled mating (cross-pollination) -self pollination -easy to manipulate -comes in a wide variety of phenotypes
Was mendel a cheat?
Mendels ratios were always very close to the theoretical expectations and the probability of getting such a high degree of congruence is 7x10^-5. It was suggested that Mendel fabricated the data.
What is a genetic map?
Morgan began to discover more linked genes and the proportion of recombinants varied depending on which genes were studied. Recombination fractions are a measure of the distance between two genes [(observed value 1 + observed value 2)/total genes observed]. Recombination fractions are additive (units are called centiMorgans)
What is mendelian inheritance in humans?
Most diseases in humans have a genetic basis, if one gene is involved it is known as a Mendelian of monogenic disease. If many genes are involved it is a multifactorial disease
What happened to the mauritius kestrel?
Native forest destruction and DDT insecticide usage caused a decline in population size. In 1974 there were only 4 left. They were examined at genetic markers called microsatellites . Those that were endangered had a low heterozygosity and the non endangered ones had a high heterozygosity.
What is satellite DNA?
Non coding DNA that experiences tandom repeats. They are nearly always harmless if mutated. They can be used in finding diseased genes, conservation and evolutionary genetics and agricultural improvement
What is continuous variation?
Phenotypes do not fall into classes and the offspring of intermediate phenotype. Does not observe mendelian ratios and has complex genetic basis plus effect of the environment. It has some quantitative traits; IQ, dermal ridge, flower shape and colour, crop yield, weight gain in animals. Genes cause continuous variation; for any locus with two alleles present in a population (A,a) there are three genotypes, and lots of genes contributing to one trait that are close together is quantitative triat locus.
How can you evaluate the evidence for the origin of man?
Phenotypically we are diverse but compared to our nearest relatives we are not very diverse. African populations are the most diverse at most types of marker and the selection. All alleles share a common ancestor. Genetic distances between DNA markers tell us when they diverged and they can calibrate genetic distances using a molecular clock. The genetic distance between chimps and humans show they diverged 5-7 million years ago. By comparing the genetic distance between humans with the human-chimp distance we can estimate the time to most recent common ancestor of all humans (TMRCA)
How can you compare balancing selection with positive selection?
Positive selection tends to cause loss of variation while balancing selection tends to maintain variation.
What is the evolutionary significance of recombination?
Recombination can produce new, fitter genotypes. Gene 1 has a allele A which enhances disease resistance and gene 2 has allele B which gives greater strength. Progeny have one copy of allele A and one copy of allele B BUT non recombinant gametes can only carry A or B. However the recombinant gamete is both disease resistant and strong. Recombination can also cause the break up of co-adaptive gene combinations as well as speeding up the rate of evolution in sexual organisms.
What is polyploidy in plants?
Related species often vary in ploidy and cannot reproduce as they have different numbers of chromosomes Bacteria are normally monoploid
Is continuous variation inherited?
Shown in twin studies. There should be a stronger correlation in monozygotic twins that dizygotic twins and should still be present when twins are reared apart. Found that both sharing of genes and sharing of environments lead to stronger correlation. Both sharing of genes and environments contribute to height
What do the phylogenies tell us?
Suggests we emerged in Africa around 120-140 thousand years which is consistent with paleontological records suggesting dates of 130-200 thousand years ago. Humans spread from Africa around 30-80 thousand ears ago which is also consistent with the Out-of-Africa model
What are the assumptions made by hardy-weinberg?
That there is random mating, there is no natural selection, there is a large population size, there is no migration and no mutation
What is mendels first law?
The Principle of segregation: The two members of a gene pair segregate from each other during the formation of gametes. Half of the gametes carry one member of the pair and the other half carry the other member of the pair
What is autosomal dominant?
The affected person usually has at least one affected parent which affects either sex and is transmitted by either sex. The child has a 50% chancee of disease (dwarfism, polydactyly)
What is autosomal recessive?
The affected usually have unaffected parents and the parents are usually carriers. It can affect either sex and theres an increased incidence of inbreeding . Carriers and non-carriers are indistinguishable and if two carriers mate their offspring have a 1 in 4 chance (albinsim, sickle cell anaemia)
What do allele frequencies measure?
The amount of genetic variation in a population in order to understand the forces that determine the genetic composition of a population (natural selection, mating system, migration, mutation and random genetic drift) as well as the genetic basis and carrier frequencies of genetic diseases
What is adaptive melanism in rock-pocket mice?
The coat colour is determined by the melanocortin 1 receptor gene (MC1R) where dark D is dominant to light d. Those that inhabit areas with light coloured sandy substrate have generally light hair, whilst those in an area with a lot of basalt gives darker haired mice. If selection was weak, allele frequencies would have been more even due to gene flow. There is evidence that positive selection has driven the dark allele (D) to high frequencies on lava flows.
What is an allele?
The different forms of a gene
What are translocations?
The exchange of parts between nonhomologous chromosomes, one of the chromosomes fuses with another at the centromere (centromeric fusion) Carriers of this are normal but their offspring can have the wrong number of copies of each chromosome
What happens when you cross red-eyed with white-eyed flies?
The eye colour must lie on the x chromosome and is the first demonstration that genes are on chromosomes. - red eyed female (XX) with white eyed male (XY) leads to red eyed males (RR) and females (Rr) in F1. In F2 you produce 3 : 1 red : white eyed flies but only males showed white eyes - white-eyed female with red-eyed male produces red eyed females (Rr) and white eyed males (Rr). In F2 this produces 1 : 1 red : white eyes with both females and males showing white eyes.
What are mutations?
The failure to store genetic information faithfully which can affect chromosomes or a single gene. They can be spontaneous or induced, harmful or neutral or beneficial and are the source of all genetic variation. They are necessary for natural selection.
How is genetic variation linked to risk of extinction?
The glanville fritillary butterfly. Found in the aland islands in finland, they are in small isolated populations, 42 are monitored and 7 have gone extinct. Several factors were examined for their effects on extinction, as extinction risk is related to environmental and genetic factors. Those that were genetically more variable had a better chance of survival. They compared the level of genetic variation in a threatened species to that in a taxonomically close but non-threatened species. Heterozygosity was 35% lower on average in threatened species. (If genetic factors are important then threatened species shouls have lower heterozygosity in >50% of paired comparisons)
What is migration?
The introduction of genes from one population to another When the population is subdivided into small isolated local populations, genetic variation can be eroded and so migration can restore genetic variation.
What is inbreeding?
The loss of genetic variation is a threat to small populations but a second is inbreeding. Small populations have fewer potential mates therefore the probability of mating with relatives increases.
What does the Human Y chromosome tell us?
The most recent common ancestor has three main branches. The Y chromosome sequence from 43 people of diverse origin suggests a TMRCA of 59 thousand years. Only one branch leads to genotypes found in Africa and elsewhere (40 thousand years)
What does mitochondrial DNA tell you?
The most recent common ancestor then has four main branches. The phylogeny using a chimp-human split is about 5-7 million years ago, and the TMRCA is about 172 thousand years. Only one branch leads to genotypes found in Africa and elsewhere (52 thousand years)
What is the evidence that small populations have a high heterozygosity?
The northern elephant seals and the mauritius kestrel. Populations that are small in size, or lack genetic variation, are less capable of evolving in response to new challenges. Genetically homogenous host populations are more vulnerable to infection than genetically diverse populations. This is called the monoculture effect.
What is a locus?
The physical position of a gene on a chromsome
What happened to the song sparrows on mandarte island?
The population crashed with 4 females and 7 males surviving. They compared inbreeding coefficients of adults and juveniles before and after the crash. The coefficient was lower after the crash so inbred birds were more likely to die
What was mendels second law?
The principle of independent assortment. The alleles of different genes segregate independently of each other. There are exceptions to the law: when two genes are physically proximate on the same chromosome they do not assort independently, and the closer they are, the greater the violation of the law
What is genetic drift?
The process of losing genetic variation by chance, that is governed by population size. Loss of genetic variation by drift is faster in small populations as they tend to be less polymorphic
What is broad sense heritability?
The proportion of genetic contributions to a population's phenotypic variance (H^2) H2 = Vg / Vp
What is the test-cross to prove mendels second law?
The seed colour gene: yellow G is dominant to green g The seed shape gene: round W is dominant to wrinkled w Seeds of genotype ggww are green wrinkled and seeds of genotype GgWw are yellow and round. If you cross them you will see 1 : 1 : 1 : 1
What is wrights inbreeding coefficient?
The standard measure of the degree of inbreeding of an individual. Teo alleles are identical by descent (ibd), if they trace their ancestry back to the same ancestral allele. f is the probability that the individuals is ibd for the locus in question, ranges from 0 to 1, 1 being the most inbred
What is the multi-regional model?
The transition from H. erectus to H. sapiens took place in many places. There was gene flow between populations. The predictions were that a single population spread over several continents connected with gene flow, populations size must have been large, humans should show high genetic diversity and no prediction that diversity should be greater in one place than others. This times our most recent common ancestor at around 1-2 million years ago
What are non-coding mutations?
There are repeat length variations and useful genetic markers. Variations in this region can be useful and mostly has little to no effect on the phenotype of the organism
What are insertions or deletions?
They are both other types of coding region mutation. They both can cause a frameshift changing all the codons from the point of indel and will cause a phenotypic difference
What is discontinuous variation?
They are discrete classes of phenotype, with no intermediates. It follows mendelian ratios and has simple genetic basis with limited effect of the environment
What are autosomes?
They are non-sex chromosomes
What is Hardy-Weinberg equilibrium?
They both independently pbserved that allele frequencies in one generation can be used to predict genotype frequencies in the next generation, and that in a random mating population the genotype frequencies are given by the ratio p^2 : 2pq : q^2
What are the causes of mutations?
They can be induced through radiation, UV or x-rays. They can be from a mutagen which is any agent that increases the mutation rate such as chernobyl or fukushima.
Who are the Amish people?
They have a small founder population from germany and marriage outside the community is forbidden. They have excellent genealogical records and pedigrees are used to understand inheritance. Theres a high incidence of some disorders such as dwarfism, polydactyly and other autosomal recessive disorders
What was the effect on population size of elephant seals in the south?
They were heavily exploited but remained abundant. Variation measured with genetic markers and heterozygosity was found to be 0.028, almost 100 fold higher than in the north .
What is the effect on population size in elephant seals in the north?
They were once abundant but were heavily exploited until they nearly went extinct. Hunting ceased and one population survived of about 20-30 individuals with only one breeding male. There are now only 100,000 world wide. The variation was measured with genetic markers, and heterozygosity was 0.00026
What is the out of Africa model?
This occurred less than 200 thousand years ago when H. sapiens emerged in Africa then spread around the globe, replacing other hominids. If humans originated in a limited area of Africa, population size must have been small. Humans should have low genetic diversity but African populations should have the greatest diversity as the theory states that all humans expanded from Africa.
What is the phenotypic variance?
Total variance of the population, includes variation from genes (Vg) and from the environment (Ve). If genetic and environmental effects are independent we can write Vp = Vg + Ve
What evidence is there that humans and other hominids interbred?
Two ancient lineages of head louse. They diverged 1.18 million years ago before human emergence. One lineage found worldwide, one had human host and the other was a different hominid
What is the chi-square goodness-of-fit test?
We expect to see (for example) equal numbers of purple and white flowers. This is a null hypothesis and to reject the null it must be greater than 3.841. The equation is the sum of the observed minus expected squared, divided by the expected. THe degrees of freedom are the number of phenotypes -1 = 1
What are deletions?
When part of a chromosome is missing, so there is only one copy of each gene in that region. The severity will depend on the size of the missing region
What are inversions?
When there are two breakpoints in the chromosome and the middle section is reversed (inverted). It can be paracentric where the centromere is exluded, often having no effect on the phenotype as there is a balanced rearrangement. It can also be pericentric which does include the centromere which can cause possible problems during meiosis as the arrangement of the centromere is now different
What is polyploidy in animals?
When two sperm fertilise the egg (dispermy) which results in three complete sets of chromosomes and happens in 1-3% of conceptions and is always lethal
What is nullisomy?
Where both members of a pair of chromosomes are missing (lethal)
What is monosomy?
Where one member of a pair of chromosomes is missing (lethal)
What is aneuploidy?
Where one set of chromosomes is incomplete as a chromosome is missing or there is an extra one.
What is trisomy?
Where there is an extra copy of a chromosome (usually lethal)
Who were the cannibal people of papua new guinea?
Women and children ate dead men meat which carried a disease. Genetic variation at the prion protein gene is associated with susceptibility to prion disease in various species. Those born after the ban on cannibalism were not subject to selection as they weren't exposed. Those born before the ban were. Heterozygotes had the highest fitness.
How do you measure the intensity of selection?
You measure the relative fitness of different genotypes which is calculated by taking the most favoured genotype as the standard with a fitness of 1.0. Example; the chance of survival for a melanic moth is only 34% of that for a typical moth in an unpolluted wood. The selection coefficients against a disfavoured genotype can be calculated as the difference between the fitness of the standard and relative fitness of the genotype in question. They measure the reduction in fitness relative to the fittest type. Natural selection caused the rapid increase in the frequency of the melanic form in polluted areas between 1848 and 1948.
How do we represent the frequency of alleles?
p + q = 1
What are substitutions?
they are coding region mutations. These can be silent (synonymous) mutations where the code can sometimes produce another codon that also codes for the same amino acid as before, so not causing any change. Or they can be replacement (non-synonymous) mutations where the amino acid coded for has changed and so will produce a phenotypic difference
