Genetics Exam 3

What is important to note about imprinting

it establishes the genes you and the next generation will express

What is genomic imprinting?

Only one parental allele is expressed (the other is silenced).

Example of imprinting?

• IGF2 → paternal allele expressed

• H19 → maternal allele expressed

Insulin like growth factor 2

expressed allele inherited from the parental side

H19

expressed allele inherited from maternal side

What is happening on the maternal allele (H19)

the enhancer is enhancing the H19 gene but cannot enhance the Igf2 gene as there is a CTCF on the inhibitor region

What is happening on the paternal allele (H19)

there is no CTCF so the enhancer can fold to enhance the Igf2 then the H19 region gets methylated so it gets turned off

What copies of the H19 and Igf2 gene do you need for somatic cells

one copy of each being expressed and another copy of each not being expressed, retains which parental chromosome it came from (i.e. funcational h19 from mom and functional Igf2 from dad)

What needs to happen for H19 gene and Igf2 gene for germ cells

need to have at least functional copy of h19 from mom, nonfunctional from dad, and then functional copy of Igf2 from dad, nonfunctional from mom

what happens if there is a mutation in the H19 gene from mom and a non-functional H19 from dad?

then you’re dead, similar if mutation in Igf2 from dad with nonfunctional Igf2 from mom

when do you incorporate methylated cytosine into DNA

not during replication, it’s after as it’s a post-replication modification

who puts the methyl group on the cytosine after DNA replication

the methyl on the parental strand signals DNA methyltransferase

what happens to the agouti gene when the maternal mouse is fed folate

becomes inactivated (methylated) so the offspring mouse appears brown

what happens to the agouti gene when the maternal mouse is not fed folate

agouti gene doesn’t get methylated so mouse appears yellow and obese

are there varying degrees of methylation of the agouti gene

yes, the more methylated the more brown the mouse gets

what is the unmethylated agouti gene

a mutation: ectopic expression

ectopic expression

gene gets expressed when and where it’s not supposed to be expressed

dominant mutation

doesn’t matter what the other phenotype is you’ll get that mutation

importance of mutations

one of the major processes that contribute to genetic variation

genetic variation provides the raw material for evolution

genetic analysis would not be possible without mutations causing variation within individual genes (serve as landmarks)

Classes of mutations

1. mutations affecting single base pairs of DNA

2. mutations altering the number of copies of genes

hardy-weinberg equation

p² + 2pq + q² = 1

what does p mean

frequency of dominant allele

what does q mean

frequency of recessive allele

what does 2pq mean

frequency of heterozygote

at equilibrium what should equal 1

p + q

hardy-weinberg equilibrium

the frequency of the alleles are not changing from generation to generation

population genetics

relates process of an individual’s genotype to the genetic composition of populations and to changes in that composition over time and space

genotype frequencies

observed proportions of genotypes in a population

many genes are what

polymorphic

polymorphic genes

multiple alleles present in a population or between different populations

allele frequency

the frequency of a specific allele in the population

genetic equilibrium homozygous a

sexually reproducing population with alleles A and a

if the frequency of a is 0.4 then the probability of either sperm or egg with a is 0.4

the probability that the fertilized egg is aa its 0.16 (0.4 × 0.4)

genetic equilibrium heterozygous Aa

two ways- Sperm: A, Egg: a or Sperm: a, Egg: A

if a is 0.4 then A is 0.6

if there are two ways of getting Aa then calculate: 2(0.4 × 0.6)= 0.48

Equilibrium distribution

AA= p²

Aa= 2pq

aa= q²

p + q= 1

when equilibrium distributions are true the gene is said

to be at hardy-weinberg equilibrium in the population

Hardy-weinberg equilibrium

sexual reproduction maintains constant genetic variation from generation to generation

unless there are events that drive the frequency of a given gene out of equilibrium

causes of changes in equilibrium

mutation

migration between populations

assortative mating between similar or different phenotypes

recombination generating new combinations

genetic drift- random sampling of gametes

natural selection

what are rare alleles

new mutations

consequence of H-W: rare alleles are rarely homozygous

allele with frequency of 0.001 is homozygous with a frequency of 1×10^-6

heterozygosity

measure of genetic variation is the amount of heterozygosity for a gene in a population

it is the total frequency of the heterozygotes

Random Mating

H-W E assumes random

EX: individuals do no choose their mates nased on blood types, in theory mating is random with respect to blood types

BUT mating is not random with respect to species as a whole which dirves populations away from H-W E

what do human psychologists believes relates to physical attractiveness

symmetry bc it means that person better developed

Why is the M/N frequency of Eskimos so different to Australian Aborigine?

very isolated populations from each other

Inbreeding

mating between individuals with common ancestry

positive assortative mating

mating between individuals with similar phenotypes (race, height)

What do inbreeding or positive assortative mating lead to

increase in homozygosity above the level predicted by the H-W E

How do you get allele frequency from a population count: AA or aa

divide the number of individuals with that genotype by the total population and multiple by 2

How do you get allele frequency from a population count: Aa

divide the number of individuals with that genotype by the total population

For H-W E to apply

mating is random

allele frequencies are the same in male and female

all genotypes are equal in viability (no selection)

mutation doesn’t occur

population is large and allele frequencies do not change due to drift

so if a population is not in equilibrium for the alleles of a given gene, one or more of these must not apply

Selection

acts by altering gene frequencies

Ex: recessive lethal tay sachs at generation 0 (at birth):

• AA: 0.81

• Aa: 0.18

• aa: 0.01

what is the frequency of a in a population

0.18/2 = 0.09

0.01 + 0.09 = 0.1

Ex: recessive lethal tay sachs at generation 0 (at reproductive age):

• AA: 0.81

• Aa: 0.18

• aa: 0.00

what is the frequency of a in the next generation

0.81 + 0.18 = 0.99

0.18/0.99 = 0.182/2 = 0.091

0.00/0.99 = 0

0.091 + 0.00 = 0.091

Ex: recessive lethal tay sachs at generation 0 (at reproductive age):

• AA: 0.81

• Aa: 0.18

• aa: 0.00

what is the change in allelic frequency

0.091 - 0.01 = -0.009 (negative change in allelic frequency)

Autosomal Recessive Diseases

frequency is 0.0001 (1 in 10,000)

If the population is in H-W E then the allelic frequency square root of 0.0001 = 0.01

Carrier frequency is approximated as 2q since p is 0.99 which is close to 1

• Carrier frequency is 1/50 = (2 × 0.01 (q))

For any given autosomal recessive disease with this frequency in the population, there is likely to be one carrier in this class

Autosomal Recessive: Individual has a sibling with the autosomal recessive disease. What is the chance of that individual having an affected child?

individual has a 2/3 chance of being a carrier

chooses mate at random, therefore mate has a 1/50 chance of b carrier

progeny has ¼ chance of being affected: 2/3 × 1/50 × ¼ = 1/300

What must happen for evolution to occur

there must be variation and it must be heritable

differential reproductive success as a function of the variation (selection)

speciation

reproductive isolation

• prezygotic - block fertilization

• postygotic

reproductive isolation: prezygotic

• geographic barriers

• temporal isolation (reproduce at different times)

• behavior isolation (mating behaviors)

• mechanic isolation - parts not fit

• gamete isolation - gametes not fuse

reproductive isolation: postzygotic

• no development of zygote

• infertile hybrid

What lead to the event of humans from chimps, gorilla, and orangutans

two chromosomes fused instead of two separate

Whale Evolution

1. freshwater habitat

2. powerful tail, shorter legs, brackish water habitat

3. saltwater habitat

4. nasal opening shifted back, eyes to side of the head

5. tail flukes, hind limbs reduced

6. loss of hind limbs, blowhole formed

7. ecolocation

who are whales related to?

hippos

populations evolve

individuals do NOT evolve

most common mechansism for speciation

geographic isolation- allopatric speciation

geographic isolation- allopatric speciation

lead to adaptive radiation- single species evolves to occupy multiple environmental niches

geographic isolation- allopatric speciation example

galapagos finches

What molecular changes can lead to differences? yellow vs brown mice in mexico

melanocortin 1 receptor: normally aplha-melanocyte stimulating hormone (aMSH) activates MC1R receptor. Ultimately induces genes that produce pigments

melanocortin 1 receptor: dark variants

the receptor has mutations that lead to constant activity even in the absence of aMSH

(dominant activating mutation)

Why does the duck have webbed feet and the chicken does not?

Chicken: expresses BMP

Duck: expresses BMP and Gremlin

gremlin prevents BMP from inducing apoptosis that gets rid of the webbing

All organisms share

a common ancestor

closely related organisms share

a more recent common ancestor than more distantly related organisms

Gene relationships arise from

phylogenetic relationships

homology

attributes shared between species because of common descent

homologs/ homologous genes

genes shared because of shared evolution

orthologs

homologs in different species that are related by descent and typically share a common function

paralogs

genes that arise by duplication (homologs within a species)

• a single gene from which a second gene arose

gene duplication can lead to either

neofunctionalization

subfunctionalization

pseudogenization

neofunctionalization

one copy keeps the original function, the other evolves a new function

subfunctionalization

the original functions are partitioned between the duplicates

pseudogenization

one duplicate accumulates disabling mutations and becomes nonfunctional

What does whole-genome duplication do

expands single ancestral chromosomal segement into multiple paralogous regions across the genome

Synteny

the conserved order and physical co-localization of genes or DNA sequences on chromosomes across different species, indicating descent from a common ancestor

synonymous mutatio (dS)

silent typos in DNA

do not change the animo acid or protein

often accumulate at a steady, clock-like rate

doesn’t structure/ function of protein

non-synonymous mutations (dN)

protein-changing mutations

alter amino acid sequence

changes structure/ function of protein

dN/dS

protein-changing substitutions/ silent substitutions

compare how often amino acid changing mutations accumulate relative to silent background changes

if dN/dS <1

purifying selection

most amino-acid changes are harmful

selection removes them

ex: conserved insulin-binding site of IGF

dN/dS >1

positive selection

protein-changing mutations can be beneficial

selection favors them

ex: genes helping tibetans at high altitude

what are the variable region for the IGF-1 gene

makes sure the conserved region ends up in the right place for function, hypothesizing that a certain region is vital to function

Haplotypes

inherited blocks of linked variants because they persist through generations. they help trace ancestry, admixture, and evolutionary history

what do haplotypes drive

linkage disequilibrium

genetic hitchhiking (the sweep effect)

natural selection can sweep an entire haplotype block through a population. Beneficial alleles pull nearly linked variants with them (genetic hitchhiking), while purifying/background selection can also remove linked variation.

both processes leave regions of unusually low genetic variation

can also track along bad alleles at the same time

Horizontal Gene Transfer

movement of genetic material between organisms other than by parent-offspring inheritance

the mechanism of HGT

foreign DNA enters the cells

integration into host genome

HGT in Eurkaryotes

Eukaryotic evolution is shaped not only by vertical inheritance, but also by occasional gene capture from viruses and bacteria. Some transferred genes became biologically important innovations

Why does HGT matter for humans

~8% of the human genome is made of endogenous retroviral sequences

Marsupials and continental drift shaping evolution

marsupials likely originated in the Northern Hemisphere or moved through North America

Their major Souther Hemisphere history involved South America, Antarctica, and Australia

These landmasses were once connected as parts of Gondwana

South America → Antarctica → Australia

Isolation allowed the Australian marsupials to radiate into

many ecological niches

Convergent Evolution

occurs when species occupy similar ecological niches and adapt in similar ways in response to similar selective pressures

analogous

traits that arise through convergent evolution

how are analogous different from homologous structures

homologous structures have a common origin, analogous don’t but do to selective pressures still evolved to have similar strucutres