Evolution and Population Genetics

Evolution and Population Genetics Xiaole Shirley Liu STAT115 / STAT215

Evolution • “Nothing in biology makes sense except in the light of evolution” • Theodosius Dobzhansky

Evolution • Evolution is a gradual change in genetic makeup from one generation to the next • Evolution: • Natural Selection • Mutation • Genetic Drift • … • Natural selection and genetic drift are the two most important causes of allele substitution in populations Nonrandom process Random processes

Evolution • Evolution creates species-specific and population-specific differences • Are they all selected for advantages to the species or population? • Some definitions: • Locus: position on chromosome where a sequence or a gene is located • Allele: alternative form of DNA on a locus • Written as A vs a, or A vs B

Natural Selection

Phenotypic vs Molecular Evolution • Phenotypic evolution is controlled by natural selection • Molecular mutations are selectively neutral in the strict sense as that their fate in evolution is largely determined by random genetic drift • Some evolutionary geneticists believe that genetic drift should be the “null hypothesis” used to explain an evolutionary observation unless there is positive evidence of natural selection Motoo Kimura

Neural Theory and Genetic Drift • Genetic drift as sampling error • Selected (sampling) copies of an allele carry the information to off springs that survive to reproduce • Sampling is subject to random variation or sampling error

Random Fluctuation in Allele Frequencies • If there is no stabilizing force returns the allele frequency towards ½, p will eventually drift either to 0 or 1, i.e. the allele is either lost or fixed in each sub-population Metapopulation Neutral alleles Deme p q p' pt … time

Allele Frequency Analogy to Random Walk Traveler staggering along a long train platform with a railroad track on either side: if he is so drunk that he does not compensate steps towards one side with steps towards the other, he will eventually fall off the edge of the platform onto one of the two tracks

Coalescence • The genealogy of the genes in the present population is said to coalesce back to a single common ancestor • The overall heterogeneity of a population will decrease • By chance, a population will eventually become monomorphic for one allele or the other

Genetic Drift • Deme: a subdivision of a population consisting of closely related plants, animals or people, typically breeding mainly within the group. • Initial mutation (allele) occurs in a deme of N individuals • Assuming neutral evolution, its probably of being sampled in the offspring is 1/2N • Over time, allele frequency will fluctuate, population diversity will decrease till allele fix or lost

Genetic Drift • Effect of population size N (N is actually called effective population size) • The likelihood of a mutation being fixed is its initial frequency (1 / 2N): it is more likely to be fixed in a small deme than in a large deme Metapopulation Neutral alleles Deme p q p' pt … time

Genetic Drift • An allele’s probability of fixation equals its frequency at that time and is not affected by its previous history • In a diploid population, the average time to fixation of a newly arisen neutral allele that does become fixed is 4N generations: evolution by genetic drift proceeds faster in small than in large populations • Demes that initially are genetically identical evolve by chance to have different genetic constitutions

Evolution by Genetic Drift • Among a number of initially identical demes in a metapopulation, the average allele frequency does not change but the frequency of heterozygotes declines to 0 in each deme Metapopulation Neutral alleles Deme p q p' pt … time

Founder Effect • Random genetic drift that ensues the establishment of a new population by a small number of colonists What would one expect from the formation of new populations by just a few individuals? Ellis–van Creveld syndrome in Amish population

Founder Effect • If the colony rapidly grows: allele frequencies will not be greatly altered from those in the source population although some rare alleles will not have been carried by the founders • If the colony remains small: genetic drift will alter allele frequencies and erode genetic variation  move quickly towards fix or lost • If the colony persists and grows: new mutations eventually restore heterozygosity to higher levels

The Neutral Theory of Molecular Evolution • 1.1. Minority of mutations are advantageous (fixed) • 1.2. Many mutations are disadvantageous (eliminated) • 1.3. Treat majority of mutations that are fixed are effectively neutral from genetic drifts

The Neutral Theory of Molecular Evolution • 1.1. Minority of mutations are advantagous • 1.2. Many mutations are disadvantageous • 1.3. Treat majority of mutations effectively neutral • 2. Most genetic variation at the molecular level is selectively neutral and lacks adaptive significance • 3. Evolutionary substitutions at the molecular level proceed at a roughly constant rate so that the degree of sequence difference between species can serve as a molecular clock

By comparing DNA changes among populations we can trace their history Population 1: A T G T A A C G T T A T A Population 2: A C G T A A C G T T A T A Population 3: A C G A A A C G T T A T A Population 4: A C G A A A C C T T A T A 3 4 1 2

From Phylogeny to Selection • The protein-coding portion of DNA has synonymous and nonsynonymous substitutions. Thus, some DNA changes do not have corresponding protein changes. • If the synonymous substitution rate (dS) is greater than the nonsynonymous substitution rate (dN), the DNA sequence is under negative (purifying) selection. • If dS < dN, positive selection occurs. E.g. a duplicated gene may evolve rapidly to assume new functions.

The Neutral Theory of Molecular Evolution • 1.1. Minority of mutations are advantagous • 1.2. Many mutations are disadvantageous • 1.3. Treat majority of mutations effectively neutral • 2. Most genetic variation at the molecular level is selectively neutral and lacks adaptive significance • 3. Evolutionary substitutions at the molecular level proceed at a roughly constant rate so that the degree of sequence difference between species can serve as a molecular clock

Molecular Clock • If protein sequences evolve at constant rates, they can be used to estimate the times that sequences diverged. This is analogous to dating geological specimens by radioactive decay. • L = number of nucleotide sites compared between two sequences • N = total number of substitutions • K = N / L, number of substitutions per nucleotide site • K = 0.093 for rat versus human Graur and Li (2000)

Molecular Clock • r = rate of substitution (mutations) = 0.56 x 10-9 per site per year • r = K / 2T  T = .093 / (2)(0.56 x 10-9) = 80 million years Over a sufficiently long time some sites experience repeated base substitutions, so the observed number of differences will plateau. Graur and Li (2000)

Where did we come from? • Two competing hypotheses • Multiregional evolution (1 millions years ago, Homo erectus left Africa, and evolve into modern humans in different parts of the Old World) • The Out of Africa hypothesis: Homo erectus were displaced by new populations of modern humans that left Africa 100K to 50K years ago.

Modern humans Europe Africa Asia Homoerectus Africa

National Geographic Story • If a fragment of DNA is shared by Neanderthals and non-Africans, but not Africans or other primates, it is likely to be a Neanderthal heirloom. • People living outside Africa carries 1-4% of Neanderthal DNA (skin, hair, etc).

Summary • Phenotype evolution (natural selection) vs molecular evolution (neutral theory) • Genetic drifts from sampling error • Decrease of genetic variation over time • Probability of fixation depends on frequency • Population size influence speed of fixation • Founder’s effect • Positive and negative selection (dN / dS ratio) • Molecular clock and migration patterns

Acknowledgement • Francisco Ubeda • Jun Liu

Evolution and Population Genetics