Lecture 7 - Genetic Drift

Genetic Drift

describes effects of sampling errors on allele frequencies (e.g., tossed coin) due to chance survival, reproduction, and inheritance events

(Essentially evolution at random as we look forward in time)

effective population size

critically important in determining the strength of genetic drift on evolutionary change

genetic drift

The elephant seals on the right are perhaps one of the poster children of…

Northern Elephant Seals

These are among the least genetically variable of mammals, but this is likely a recent phenomenon due to a combination of human caused population reductions and the life history of these interesting creatures.

• Overhunting in the mid 1800’s reduced the population to fewer than 40 individuals (now there are more than 100,000)!... So, they went through an extreme population bottleneck

• Also, only small numbers of males successfully mate because males essentially guard harems, meaning that the effective population size of this species is extremely low.

lack

Northern Elephant Seals have a ______ of genetic variability

how many individuals in each population are contributing their alleles to succeeding generations, basically who breeds and how successful they are

To estimate genetic drift, we need to know…

equally

Drift is truly random and unbiased, so allele frequencies are _______ likely to go up or go down

smaller

Random fluctuations in allele frequency are larger in smaller populations and thus drift is stronger in _________ populations

different

Drift causes populations that are initially identical to become ________ (each color in these plots is a different population) and basically variation is lost, it moves away from 50:50 allele frequencies

fixation of alleles

Therefore, drift causes populations to differentiate by ____________ without the action of natural selection.

weak

When populations are extremely large drift is extremely _______.

diverge

If genetic drift runs across many genetic loci, then it causes populations to ________.

coalesce

•When the lineages of two gene copies merge we say that they _______

a single ancestor

Tracing the genealogy or ancestry of gene copies through time, ultimately all “living” copies of a given gene in a population are descendants of…

Genetic drift

So, when we say that the number of descendants left by different copies of the gene are random, what do we mean by random here?  What is the evolutionary process that is acting on the numbers of gene copies that are passed on to the next generation?

maternally

First, mtDNA is inherited _________, all of us get our mtDNA from our mothers and not our fathers.

female

This diagram is a genealogy tracing all human mtDNA backward in time to the most recent common ancestor which had to be a ______, the so-called mitochondrial eve.

~125,000

Mitochondrial eve lived _______ years ago

male

We can use a similar process to look at the ancestry of the Y chromosome and trace it back to a single _______ human ancestor

lived 8 mya in the ancestor of humans and chimps

for example, we know that the mtDNA that all humans carry and the mtDNA carried by our closest relatives the chimpanzees are descendants of mitochondrion that _____________ before our lineages split

a common ancestor at some time in the past

What this means is that if we look at any two copies of a gene, they ultimately share…

genealogies

-different genes can have different…

individuals

what this means is that _________ gene trees don’t always match species trees

longer

the larger the population size the _______ the time it takes for two copies of a gene to coalescence at a common ancestor

variation

Because drift is random and coalescence involves drift, there is a lot of ________ around the average coalescence time if we look at different pairs of genes

time

coalescence still applies if selection (or other evolutionary forces) are active, but this changes the _____ to common ancestor from two descendant gene copies

speciation event

Basically deep coalescence events are events where the coalescence of “living” alleles traces further back in time, well before the _________.

different topologies

Basically deep coalescence in combination with incomplete fixation of gene lineages within species lineages (incomplete lineage sorting) may result in a gene tree and species tree with…

mismatch

“Lineage sorting” of ancestral polymorphism can cause ________ of species tree and gene tree. “Lineage” here refers to gene lineage not species lineage.  

effective population size

the strength of genetic drift is driven in part by population size, in particular a parameter that we call…

idealized; strength

Effective population size N_e is an __________ population and we used effective population size to measure the _________ of drift

N_e

the # of individuals that would give the idealized population the same strength of drift as an actual population of interest

less

N_e is always ________ than the actual population size because

-populations naturally fluctuate in size

-populations usually have uneven sex ratios

-juveniles and older individuals in populations don’t reproduce

-reproductive success is variable among breeding age individuals

-dispersal of individuals away from their birthplace is limited

strong

Small N_e means ______ drift

weak

large N_e means ____ drift

•Bottleneck

population reduced to small size for a few generations

•Founder effect

genetic drift that accompanies start of new population where a founder colonizes a new area. Allele may not be included in new population, or under- or over-represented by chance.

Small

_______ founding population is subject to rapid fixation/loss of alleles

small

 loci tend toward homoallelism (monomorphism) in very _______ populations

small

Therefore, _____ populations tend toward decreased variability, less for selection to act on (there is also a lower chance of mutation generating new alleles because there are fewer individuals)

reduce

•Bottleneck and founder effect both _______ genetic variation

heterozygosity (pi)

the chance that two chromosomes in a population have different nucleotides at a given site (a measure of genetic diversity)

highest; lowest

Diversity is _______ at the source and ________ furthest away from the source, basically as colonization occurs this creates multiple founder events and reduces population sizes, which ultimately reduces genetic variation in these small founding populations.

reducing

Successfully breeding individuals will show variation in reproductive success, sometimes at random and sometimes due to selection (elephant seals). This means…

•Some parents donate more alleles than others, ________ effective population size

-sometimes sex ratios at birth are biases

-sometimes females and males survive differently

Uneven sex rations are also a key factor causing Ne to be smaller than actual population size. Sex ratios can vary in populations or species for many reasons…(2 given)

genetic drift

The fate of advantageous mutations in a population is not only determined by natural selection; _________ can also add a random component to the trajectory of the frequency of a given mutation and drift is stronger at smaller effective population sizes

fixation

it takes more generations for _______ to occur at N_e = 50 versus N_e = 5.

p = frequency of one allele and N_e and fixation time is proportional to effective population size (N_e)

Equation for time to the fixation of one of two alleles at a locus depends on two parameters:

   -4N_e [p ln(p) + q ln(q)] generations

•Time for fixation of one of two alleles at a locus is…(equation)

smaller

Large organisms tend to have ______ N_e

higher

E. coli, a widespread and common bacterium has an N_e much ______ than any of the animals

single nucleotide polymorphisms (SNPs)

•Humans:  99.9% of base pairs identical between two randomly chosen humans, considering only ________ across 3.2 billion base pairs of DNA

0.45-0.75

•Mean heterozygosity in human populations higher: _______, based on different haplotypes

1.6%

Counting all possibly differences (insertion/deletion; copy number variation; inversions), differences between two humans can be ____

against

So why do we see this non-random distribution of polymorphisms

-mutations in coding regions can cause amino acid changes (which may not be selectively neutral) so there are constraints on mutations in coding regions that select ________ mutations in these  areas

neutral

So why do we see this non-random distribution of polymorphisms

-mutations in non-coding regions or in regions of exons that don’t change amino acids (e.g. 3^rd codon positions) are selectively ______ and thus the polymorphism evolves via genetic drift

π ≈ 4 N_e µ_n   when π is ≤ 0.1

Heterozygosity from neutral mutations evolving by drift in diploid expected to be: (u_n is the rate of neutral mutation, the chance per generation that the locus mutates to another allele that does not change the organism's fitness)

Polymorphism

__________ increases with both effective population size and with neutral mutation rate

purifying selection

Deleterious alleles are weeded out by ________, basically these are alleles that are loci under selective constraints

purifying selection

In non-coding regions heterozygosity is typically higher because the neutral mutation rate approaches the actual mutation rate because there is little to no…

reduce

Both background selection and selective sweeps _______ polymorphism across populations

fixation

Selective sweeps can happen where strong positive selection on a beneficial allele causes that allele to go to _______ and therefore genetic variants or mutations located near the beneficial allele also increase

reduced

Heterozygosity is _______ by selective sweeps and background selection near center and ends where recombination is lower.

stronger

Selective sweeps and background selection are ________ where there is less recombination, because selectively advantageous or disadvantageous alleles are in stronger linkage disequilibrium (a stronger statistical association of alleles) with nearby alleles when there is less recombination

strongly

Fecundity and propagule size also _________ correlated with heterozygosity.

heterozygosity

Differences result from variation in population sizes, and other factors, so lower population sizes and lower fecundity have lower __________ and vice versa

slowly; quickly

As N_e is higher (and thus drift is weaker) that fixation due to selection proceeds more ______, and that when N_e is lower and thus drift is stronger, selection acts more ______ to drive alleles to fixation

much more powerful than

•For species that have large N_e (e.g., D. melangogaster, E. coli) selection is _________ drift for alleles with advantage as small as s = 10^-5.

–Can lead to precise adaptations like codon bias; different codons that are synonymous can effect accuracy and efficiency of translation and thus the genomes of species with high N_e are biased toward these efficient codons (selection for more efficient codons)

–In closely related species, about half of amino acid differences in proteins evolved by positive selection, other half fixed by drift.

drift

•For species with small N_e most fixation is by ______.

–Only ~15% of differences between proteins of humans and macaques result from natural selection.

–Many mutations that reduce fitness by 10^-5 fixed by drift.

increased

In inbred population of Adders (snakes) in Sweden, introducing individuals from other populations reintroduced alleles that had been lost to drift resulting in ________ survival of offspring.

adaptive divergence

Outliers can tell us about _________ of populations.