Integrative Biology 35AC EXAM 2

What can explain the ability to digest lactose?

#Not migration-we would see a general spread and we don't; need candidate source of population; migration tends to eliminate differences in allele frequency # not drift - we would expect it to occur in small populations, thus lactase persistence would have to be selectively neutral #selection - provides a sort of advantage, not sexual but natural why do we still drink milk as adults -hormones, imuno factors, water, milk fat sugar (energy), vitamins: vitamin A, minerals: calcium, hormones: cortisol (help infant function and develop and helps infant know mom's mood), immunofactors:secretory immunoglobin,water: H2O (main sory of infants getd

Sweat

-Glands diff expressed depending on age - express diff vibes at diff ages -we became darker and sweatier and less hairy so sweat can run off (more mobile)

genetics of lactase persistence

-Trait control by snp in regulatory region of the lactase gene

PASTORALISM

-culturally Economy in which cattle, sheep, goat, camel, etc. and their milk, meat, and blood are the major component. • Dairy animals are useful even if you can't drink their milk, but they are much more so if you can. - mult pops have different genes corresponding for lactase persistence-convergent evolution

MCIR gene

-melanocortin 1 • mutations at this gene

Genetics of obesity

-melanocortin-leptin pathway: MC4R gene and leptin defiency -complex interactions: polygenic, age effects, gene-by-environment effects, gene-by-sex effects, environment-by-sex effects • Normally an increase in leptin after eating but these people have a leptin deficiency ------------------- some racial groups have higher rate (hispasnics, blacks) ------------------- Gwas (genomic wise association studies) • Large population of people obese - trying to compare SNPs/loci with trait in population -------------------- Linage analysis • Some people obese, some people not obese compare people • More helpful for studying gene that is really rare -study associated of loci with trait in a pedigree with the affected individuals involed ----------------------- Identified genes only explain 1.4% of varitation

lack of vitamin D

-rickets ( to females can causes severe malformation of pevis) which ---> • Worldwide, maternal hemorrhage is the 4th leading cause of death for women in their reproductive years (accounting for 123 deaths per 1000). In low-income countries, it's the 3rd, just below HIV and tuberculosis. HIV is the #1 killer of women of reproductive age worldwide. • (In high income countries, it's suicide, followed closely by car accidents.) ----------------- OBSTETRIC FISTULAS • According to the WHO, it is estimated that more than 2 million young women live with untreated obstetric fistula throughout the world, mostly in parts of sub-Saharan Africa and Asia.

Hypothesis for environmental mismatch for obesity

-thrifty genotype • mediated by difference by gene frequencies • comparing genes • not changing gene itself but changing way it is expressed - epigenetics (changing the way genes are expressed not their sequence) o Dutch famine cohort study: women pregnant during famine, children more likely to be obese

what proportion of adults produce lactase

1/3

Evolution

A change in allele frequencies over time.

DARK SKIN WAS THE ANCESTRAL CONDITION OF OUR SPECIES

A high melanin content was needed to protect the naked skin of active people in extremely sunny environments.

SUMMARY: LACTOSE INTOLERANCE

All children can digest lactose. • Lactose intolerance is the condition of most adults. • The high frequency of adults in certain parts of the world able to digest lactose [lactase (+)] is a product of natural selection in a culturally created environment of pastoralism.

Sexual Selection

Any trait that confers mating and fertilization advantages, and is passed down to offspring, will increase in frequency in the population over time

UVR (100-400 NM) PROFOUNDLY AFFECTS BIOLOGICAL SYSTEMS

Damage to DNA • Inhibition of photosynthesis in phytoplankton • Damage to cell membranes • Photolysis of bioactive compounds (folate, vitamin B12) • Catalyzes pre-vitamin D3 synthesis

THE EVOLUTIONARY ADVANTAGE OF DARK SKIN

Dark skin acts as a natural sunscreen, and protects against breakdown of folate by UVR. • Don't lighten your skin!

CORRELATIONS: SKIN COLOR WITH AVERAGE UVR

Filter UVMED (Average) 685 nm (red) -0.815 545 nm (green) -0.903 425 nm (blue) -0.891 As UV radiation increases, skin color gets darker (skin reflectance decreases)

FOLATE AND HUMAN DEVELOPMENT

Folate is needed for all processes requiring cell division, especially in early embryonic development and in the production of sperm

PRNP GENE M and V ALLELES

Gene responsible for prion disease; Part of mortuary rituals is to eat the brain, women and children expectd to eat brain (developed kuru) • 129th codon, strong susceptibility factor for human prion diseases. • Homozygotes of either allele have a younger age at onset. • 23/30 Fore women over age 50 who had partaken in multiple mortuary rituals were heterozygote at codon 129. • Argued to be balancing selection, those that were heterozygote for the M and V alleles resisted developing kuru • More recent & larger study suggests that globally the low variation in this gene is likely purifying selection & episodic events such as seen in the Fore.

• We inherit two kinds of information from our ancestors:

Genetic,Cultural

Cowboy wash, SW colorado

Human myoglobin on pottery fragments and in a coprolite (evidence of fossilized poop) with human muscle tissue digested within it)) AD 1150

Carleton Gajdusek

In 1976 became co-recipient of the Nobel Prize in Medicine for his "discoveries concerning new mechanisms for the origin and dissemination of infectious diseases."

KITLG (KIT LIGAND)

In stickleback fish, light-skinned populations have a divergent allele of Kit ligand gene • In humans, Europeans and East Asians also have derived alleles at the KITLG locus • Regulatory regions of KITLG have evidence of strong selection (humans) • Convergence or conserved mechanism in fish and humans for lighter pigmentation • Miller et al. 2007. Cell 131:1179-1189.

RECENT RISE OF RICKETS due to poorly adequeate environments for skin color

In the UK, perhaps 20% of children from all social classes show signs of the disease.

What does melanin do?

MELANIN REGULATES THE AMOUNT OF SUNLIGHT ENTERING THE BODY, melanocytes hold in melanin (keeps radiation from entering deeper into skin)

WHAT GIVES SKIN ITS COLOR?

Melanin- gives brown tone • Carotene - orange tone • Hemoglobin - gives red tone

INT((PickM((E)))RSEXUAL SELECTION

Members of of one sex choose which individuals of the other sex to take as mates.

INTR((R(A)WR))SEXUAL SELECTION

Members of one sex compete with each other for access to the other sex

Lactase Hotspots

Only one-third of people produce the lactase enzyme during adulthood, enabling them to drink milk

PRIONS

Proteins that have folded inappropriately and bump into other proteins causing them to fold inappropriately as well • Really surprising that something without any genes could cause infections, simply malformation of proteins (proteins don't contain genes, rather they are what genes code for)

SKIN COLOR IS MEASURED BY

SKIN REFLECTANCE

SPONGIFORM ENCEPHALOPATHIES in other species

Scrapie (sheep and goats) • Chronic wasting disease (mule deer and elk) • Transmissible mink encephalopathy • Feline spongiform encephalopathy • Exotic ungulate encephalopathy (greater kudu, nyala, oryx) • Bovine spongiform encephalopathy (mad cow disease) 1986 - [first identified in England (dead sheep) - Methods for processing sheep carcasses were risky (1970s-1988) -The epidemic has probably peaked

conclusions for skin

Skin pigmentation is an evolutionary adaptation for regulating penetration of UVR into the skin. • Skin pigmentation represents a compromise between the demands of protecting the body and making enough vitamin D. • Skin pigmentation can change in response to environmental conditions over thousands of years. • Dark and light skins have evolved many times in human history

FEMALES ARE LIGHTER

THAN MALES

THE FARTHER FROM THE EQUATOR YOU LIVE

THE HARDER IT IS TO MAKE VITAMIN D

LACTOSE INTOLERANT ETHNIC GROUPS

The distribution of lactose intolerance around the world is not uniform...

UNDER WHAT CONDITIONS IS DARK SKIN NOT AN ADVANTAGE?

The melanin in dark skin slows the production of vitamin D. • This is a problem in areas that don't receive much sunshine.

Epidemiology

The science of disease occurrence and transmission.

WHY ARE WOMEN LIGHTER?

They must produce as much vitamin D as possible during their reproductive years. • Their skin color has been defined at the "knife's edge" of natural selection.

MC1R GENE

This gene makes a protein that affects the color of skin and hair. Regulates how much melanin or pheumelanin is produced (our ancestral trait is to have very dark skin and we kinda derived lighter skin (if compared to first humans (apes it is a primitative trait)) "At this locus, amino acid differences are entirely absent among African humans, abundant among nonAfricans (especially Europeans), and abundant in chimpanzee/human comparisons... "

Stanley Prusiner

UCSF 1997 Nobel Prize in Medicine Prize motivation: "for his discovery of Prions - a new biological principle of infection"

YOU NEED SOME UVR TO MAKE VITAMIN D IN YOUR SKIN

Vitamin D is needed to build and maintain strong bones, and to maintain a healthy immune system., metabolism of vitamin D

NATURAL SELECTION - the reason for lactase persistence

[[[• A new caloric source is available to individuals who remain able to digest milk their entire lives [lactase (+)] ;food value ;water content ; improved calcium intake ]]]] -This allows them to live longer and produce more offspring than their lactase (-) neighbors • Those offspring are also able to digest milk • The population gene frequency shifts towards lactase (+) - only one-third of people produce the lactase enzyme during adulthood

oligogenic

a few genes controlling the trait

White people reflect

a lot more light and reflect a lot more red

darker skin people

absorb a lot more light

types of inheritance

autosomal recessive, autosomal dominant, autosomal codominant (distinct heterozygote phenotype) • Autosomal dominant o Ex's marfan's syndrome, • Autosomal recessive : cystic fibrosis, Attached ear lobe- ( Trait can skip generations, can be masked) • Autosomal codominant - • anytime dominant allele produces phenotype o Ex's hair curliness, eye color

Human adaptations - something that enhances fitness

bipedalism, hairlessness, pigmentation

ozone layer in atmosphere

blocks UVC rays from reaching skin

spongiform

brain looks spongy

• Human cultural practices ...

create highly selective environments in which our genomes have evolved.

SPINA BIFIDA

cyst on babies back, incomplete closing of the embryonic neural tube

encephalophathis

disease of brain

Lactase

enzyme that digests lactose into parts that can be used by your body

SLC 45 ac

europens this mutations allowed their niches to change

variant CJF

exposure eating priorn infected cow meat

RICKETS IN SAUDIA ARABIA

females forced to wear extremely conservative clothes, can't synthesize any vitamin D

we all have the same number of melanocytes BUT

funcionatlity differs depending on individual

Purifying selection - getting rid of alleles from genome

gene is being pushed out completely by killing of children before can reproduce

MV genotype advantageous

heterozygote advantage or balancing selection

folate

important for neonatal tubing. Too much UVB radiations harms this and causes birth defects.

Lactose digestion graph

lactose goes all the way through digestion system. Lactase turns into glucose and galactose, then poop -lactose intolerant- lactose is met by bacteria and water which formulates gas, organic acids, irritation - increased motility (diahhrea)

locus

location on the chromosome

polygenic

many genes controlling trait

Lactose

milk sugar Mammals - produce milk to feed young -extremely nutrional, human naturally change nutrition of milk depending on sex of baby, breast milk will continue to produce milk as long as stimulus is presented

fauna

not plants, all other living organisms

monogenic

one gene controlling trait

Niche

place where animals fit in , all the necessary conditions for a species

Hertiability of hair

relatively small number of SNP's can predict eye and hair color with high accuary • EDAR gene influences hair thickness, disease phenotype at one extreme of the distribution

Purifying selection

removal of a certain allele due to deletrerous effect on fitness

UVB rays penetrate epidermis...

this prompts melanocytes to make melanin pigment, which is packaged in structures called malanosomes. malanosomes are taken up by keratinocytes toshield their DNA by forming a nuclear cap

• pops with a high freq of lactase persistence

us whites, Swedish, swiss, and others

vitamin d process

uvb-> catalyze previt D -> synthesize vit D

WE don't not absorb vitamin D from the sun

we use it to synthesize the reaction and then we absorb vitamin D

biotioc

whats alive in an ecology, bugs , plants

abiotic

whats not alive - soil

pastroialism areas

• -norther europle and afric • domestication of live stock 10,000 yrs ago prior to

WHAT IS AN ADAPTATION?

• An adaptation is something that enhances the survival and reproductive success of an organism in a particular environment.

SO WHY DID LIGHT SKIN EVOLVE?

• As people moved away from the equator, their skin had to lose pigmentation in order to permit them to continue to make adequate amounts of vitamin D in their skin.

GENETICS OF SKIN COLOR

• At least 26 genes appear to be involved in determining skin color • A few recent studies: • KITLG (Kit ligand) • MC1R • Convergent evolution

Kuru epidemic

• Epidemic started in the 1940s • Early research noted the family clusters of the disease and thought it was inherited • But further research showed otherwise • Prions (pronounced "pree-ons") • PRNP gene, M and V alleles at the 129th codon

CANNIBALISM

• Exocannibalism: selectively eat people from outside group • Endocannibalism: eat ppl from own group (rituals) • Autocannibalism: eating yourself • Survival cannibalism: eating to survive • Pathological cannibalism: you're crazy so you're eating people

THE LCT GENE

• First discovered in the 1980s • 2002 discovered a regulatory region 14,000bp away from the gene that correlates with lactase persistence in Europeans • Tishkoff & colleagues studied 43 African ethnic populations and found a different regulatory region that correlates with lactase persistence.

UVR AFFECTS REPRODUCTION BY BREAKING DOWN VITAMINS

• Folate (from the B Vitamin group) is broken down by UVA. • Folate deficiency slows the production of DNA.

OTHER POTENTIAL CULTURAL SOURCES OF TRANSMISSIBLE HUMAN SPONGIFORM ECEPHALOPATHIES

• From infected beef... ; Packed feedlots ; Feeding processed beef parts to cattle ;Lax US regulatory compliance ; Last case of BSE: April 2012 - got rid of the cow ;Las case of vCJD: June 2014 - guy in austin texas died -------------- • From unregulated population growth in deer...?: No natural predators ; During harsh winters, deer resort to cannibalism ;Three cases of spontaneous CJD in the US in1998 had eaten venison

Hertiability for height

• High heritability - close to 1 - close association with parents and offspring • If no heritability- just clusterd • 60 to 80% of the difference in height between individuals is determined by genetic factors • 20 to 40% can be attributed to environmental effects • Total phenotypic variation in one population may be greater than phenotypic variation in another. BUT, the variation due to the genetic effects is usually the same across populations. • Height is a polygenic trait, and different genes have significant effects in different populations.

SKIN PIGMENTATION REGULATES THE PENETRATION OF UVR INTO THE SKIN

• It determines both the rate of breakdown of UVR-sensitive compounds and the production of UVR-dependent compounds

WHY STUDY HUMAN SKIN COLOR?

• It represents the product of over five million years of evolution • It is one of the most obvious ways in which people vary • It is important to humanity

HUMAN PRION DISEASES

• Kuru ("laughing death") • Gerstmann-Staussler-Scheinker disease - fatal over longer period of time • Fatal familial insomnia - mutation causing people to develop malformed proteins a lot easier • Creutzfeldt-Jakob disease - brain esentially melting, seen more in old people;Occurs world-wide, sporadically ; 1 in 1,000,000 around age 60

PIGMENT IN NEANDERTHALS

• Lalueza-Fox et al. 2007. Science 318:1453-5. • Amplified and sequenced a fragment of the MC1R gene from 2 Neanderthal remains • Both have a mutation not found in the 3,700 humans studied • The mutation impairs function of MC1R

POTENTIAL DANGER OF SUN BEDS

• Lapunzina (1996) reported the occurrence of NTDs in three subjects whose mothers had been exposed to UVR on "sun beds" during the first three weeks of their pregnancies. • California State Law • Senate Bill 746, took effect Jan. 1, 2012 CA State Sen. Ted W. Lieu of Torrance • Lieu's law, known as Senate Bill 746, took effect Jan. 1, 2012 and bans children under the age of 18 from using UV-emitting tanning beds. It won bipartisan support and other jurisdictions, in addition to Texas, have recently emulated California's law, including Vermont and Chicago

PARALLEL EVOLUTION

• Light skin has evolved several times in our lineage, and at least twice in modern humans. • The light skin of Europeans and Asians is an example of evolutionary convergence.

HUMAN SKIN COLOR IS ADAPTIVE in that...

• Melanin pigmentation varies by latitude and is related to many latitude-dependent environmental parameters. • Darker skin protects against the deleterious effects of UVR (e.g., sunburn, damage to sweat glands, skin cancer).

LACTASE ALLELES

• Mutated allele (lactase persistent)[ -lactase (+) or lactose tolerant -body can digest milk - infants are all lactase (+) ] • Normal allele [ -lactase (-) or lactose intolerant - body cannot digest milk -bacteria digest milk instead]

FOUR FORCES OF EVOLUTION

• Mutation (the only source of new variation) • Selection (acts to diverge populations directionally) • Drift (acts to diverge populations randomly) • Migration (the 'genetic glue' that hold populations together)

STUDYING SKIN COLOR REQUIRES THAT YOU STUDY UVR

• NASA • Total Ozone Mapping Spectrometer (TOMS) between 1978 and 1993 • Data comprises 37,400 readings for each day

HUMAN SKIN COLOR IS NOT ADAPTIVE in that...

• Sunburn and skin cancer rarely affect reproductive success. • Skin color is a byproduct of selection on other functions of pigmentation genes. • Skin color has evolved as the result of sexual selection.

LACTOSE INTOLERANT ETHNIC GROUPS

• The distribution of lactose intolerance around the world is not uniform...

GENES INFLUENCING VARIATION IN SKIN PIGMENTATION

• The melanocortin 1 receptor (MC1R) locus, which regulates melanin production, shows little variation in African populations, but exhibits extensive allelic variation in European populations (Sturm et al., 2001). • The DCT gene shows evidence of selection in a Chinese population (Myles et al., 2006) • MATP, SLC24A5, OCA2, and TYRP1 show evidence of selection in European population (Myles et al., 2006)

WHAT IN THE PHYSICAL ENVIRONMENT IS MOST CLOSELY RELATED TO SKIN COLOR?

• Ultraviolet Radiation : UVA - completely can enter skin (wrinkly skin, premature aging) , UVB - really harmful part of UV radiation (skin cancer, cataracts, sun burn) , UVC - extremely dangerous ( blocked by ozone layer)