Population GeneticsPopulation Genetics

I.I. What is population genetics?What is population genetics?A.A. Studying Variation Studying Variation

B.B. Gene frequencies & allele frequenciesGene frequencies & allele frequencies

II.II. Hardy-Weinberg equilibriumHardy-Weinberg equilibrium

III.III. Factors that change allele frequencies Factors that change allele frequencies in populationsin populations

I. What is Population GeneticsI. What is Population GeneticsGoalGoal: understand the genetic composition of a : understand the genetic composition of a population and the forces that determine and population and the forces that determine and change that compositionchange that composition

Fundamental measurement = allele frequencyFundamental measurement = allele frequency

Forces that change allele frequency = mutation, Forces that change allele frequency = mutation, selection, gene flow, genetic driftselection, gene flow, genetic drift

Side-blotched lizards (Uta stansburiana) in central California experience unusual patterns of throat color.

Terms for understanding genetic diversityTerms for understanding genetic diversity

Population, subpopulation, local population Population, subpopulation, local population Genetic structure = genetic composition of a Genetic structure = genetic composition of a

given population given population Based on analysis of Polymorphic lociBased on analysis of Polymorphic loci Only an estimate at that given moment in timeOnly an estimate at that given moment in time

Genotype frequency = # individuals with a Genotype frequency = # individuals with a particular genotype in a pop / Nparticular genotype in a pop / N

Allele frequency = # of copies of an allele in Allele frequency = # of copies of an allele in a pop / total # alleles in a pop.a pop / total # alleles in a pop.

Genetic PolymorphismGenetic Polymorphism

Genetic Structure

Allele Frequency

Gene Frequencies & Allele FrequenciesGene Frequencies & Allele FrequenciesGene frequency refers to proportion of particular allelic Gene frequency refers to proportion of particular allelic form among all copies of gene in populationform among all copies of gene in populationUsually estimated by sampling populationUsually estimated by sampling population diploid: 2 copies of genediploid: 2 copies of gene

homozygotes: 2 copies of allelehomozygotes: 2 copies of alleleheterozygotes: 1copy of each alleleheterozygotes: 1copy of each allele

haploid: 1 copy of allelehaploid: 1 copy of alleleFor two alleles, For two alleles, pp + + qq = 1, where = 1, where pp and and qq are frequencies are frequencies of the two allelesof the two alleles

Calculating Genotype FrequenciesCalculating Genotype Frequencies

The proportion of individuals The proportion of individuals in a population with a in a population with a particular genotypeparticular genotype

ffA/A = # of A/A divided by A/A = # of A/A divided by the totalthe total

ffA/a = # of A/a divided by A/a = # of A/a divided by totaltotal

ffa/a = # of a/a divided by a/a = # of a/a divided by totaltotal

A/AA/A A/aA/a a/aa/a

NN 4040 4747 1313

ff 0.400.40 0.470.47 0.130.13

Relative frequencies of genotypes – proportion of organisms that have the particular genotype

Calculating allele frequenciesCalculating allele frequencies

If If ffA/A, and A/A, and ffa/a are the proportions of the a/a are the proportions of the three genotypes at a locus with two three genotypes at a locus with two alleles, then the frequency p(A) of the A alleles, then the frequency p(A) of the A allele and the frequency q(a) of the a allele allele and the frequency q(a) of the a allele are obtained by counting alleles:are obtained by counting alleles:pp = = ffA/A + ½ A/A + ½ ffA/aA/aqq = = ffa/a + ½ a/a + ½ ffA/aA/app + + qq = = ffA/A + A/A + ffa/a + a/a + ffA/a = 1.00A/a = 1.00qq = 1 – = 1 – pp and and pp = 1 – = 1 – qq

AAAA AaAa aaaa totaltotal

NN 4040 4747 1313 100100

# of A# of A 8080 4747 00 127127

# of a# of a 4747 2626 7373

TotalTotal 200200

Allele Frequency of A = 127/200 = 0.635p(A) = 0.635Allele Frequency of a = 73/200 = 0.365 q(a) = 0.365 = 1 - p

Mendelian considerations in population genetics…

II. Hardy Weinberg equilibriumII. Hardy Weinberg equilibrium

Sexual reproduction does not cause a Sexual reproduction does not cause a constant reduction in genetic variation in constant reduction in genetic variation in each generation; rather the amount of each generation; rather the amount of variation remains constant generation after variation remains constant generation after generation generation in the absence of other in the absence of other disturbing forcesdisturbing forces..Model that shows what happens to allele Model that shows what happens to allele and genotype in an “and genotype in an “idealideal” population ” population using a set of simple assumptionsusing a set of simple assumptions

Populations in HW equilibrium have Populations in HW equilibrium have the following properties:the following properties:

1)1) The frequency of alleles does The frequency of alleles does notnot change change from generation to generationfrom generation to generation

2)2) After one generation of random mating, After one generation of random mating, offspring genotype frequencies can be offspring genotype frequencies can be predicted from the parent allele predicted from the parent allele frequenciesfrequencies

3) Why use HW?

It Identifies the real-world forces that change allele frequencies

80% of all the gametes in the population carry a dominant allele for black coat (B) and 20% carry the recessive allele for gray coat (b).

Random union of these gametes will produce a generation: p2 = 0.64 2pq = 0.32 q2 = 0.04

So 96% of this generation will have black coats; only 4% gray coats.

Will the gray phenotype eventually be lost?

Testing for equilibriumTesting for equilibrium

1)1) Determine the genotype frequenciesDetermine the genotype frequencies Directly from phenotypesDirectly from phenotypes Analyzing DNA sequenceAnalyzing DNA sequence

2)2) Calculate allele frequenciesCalculate allele frequencies

3)3) Predict the offspring’s genotype Predict the offspring’s genotype frequencies using HW principle… does frequencies using HW principle… does the prediction hold true? Are they similar the prediction hold true? Are they similar to the observed frequencies?to the observed frequencies?

CCR5 genotype exampleCCR5 genotype exampleN = 238N = 238

223 – 1/1, 223 – 1/1, 57 – 1/Δ32, 57 – 1/Δ32, 3 - Δ32/Δ323 - Δ32/Δ32 ff(1/1) = 0.788, (1/1) = 0.788,

ff(1/Δ32) = 0.201, (1/Δ32) = 0.201, ff(Δ32/Δ32) = (Δ32/Δ32) = 0.0110.011

p = 0.89 q = 0.11

Expected genotype frequency:p2 = 0.7922pq = 0.196q2 = 0.012

The allele frequency for hemophilia (The allele frequency for hemophilia (A)A) is is 1/10,000 or 0.0001. 1/10,000 or 0.0001.

a)a) What is the allele frequency for the normal What is the allele frequency for the normal allele in the human population?allele in the human population?

b)b) Among males, what is the frequency of Among males, what is the frequency of affected individuals?affected individuals?

c)c) Within a population of 100,000 people, what Within a population of 100,000 people, what is the expected number of affected males? is the expected number of affected males? What is the number of expected carrier What is the number of expected carrier females?females?

III. Factors that change allele frequencies in III. Factors that change allele frequencies in populations: Disturbing forcespopulations: Disturbing forces

1)1) MutationMutation

2)2) Non-random matingNon-random mating

3)3) Gene flowGene flow

4)4) Genetic DriftGenetic Drift

5)5) Natural selectionNatural selection

1) mutation1) mutationMutation is the Ultimate source of variation, playing a fundamental role in the process of evolutionMutation rateMutation rate (μ)= probability that a copy of an allele (μ)= probability that a copy of an allele changeschanges to some other allelic form in one generation Δq = μp

p = 0.8, q = 0.2, μ = 10p = 0.8, q = 0.2, μ = 10-5-5, , Δq = (10-5)(0.8) = 0.000008)

Next generation:Next generation: qn+1 = 0.2 + 0.000008 = 0.20008 pn+1 = 0.8 – 0.000008 = 0.799992

Mutations don’t significantly alter allele freq. In 1 generation…Gets slower every generation

2) Gene flow2) Gene flowGene Flow = migrationGene Flow = migration Gene flowGene flow - Genetic exchange between - Genetic exchange between

populations due to the migration of populations due to the migration of individuals between populationsindividuals between populations

Can offset the effects of genetic driftCan offset the effects of genetic drift Inhibited by isolationInhibited by isolation

3) Genetic Drift3) Genetic DriftGenetic DriftGenetic Drift Random fluctuations of allele frequencies Random fluctuations of allele frequencies

between generationsbetween generations compounded by compounded by small populationsmall population size size alleles can become fixedalleles can become fixed

The genetic bottleneck effect

Founder effect, similar outcome… due to chance, the allele frequency in the founding population may differ from the original population.

4) Inbreeding (non-random mating)4) Inbreeding (non-random mating)

Inbreeding = Mating between relativesInbreeding = Mating between relatives

IDBIDB – – i identical dentical bby y ddescent, the two alleles escent, the two alleles may be copies of the same gene in an may be copies of the same gene in an earlier member of the lineearlier member of the line

5) Natural selection5) Natural selectionThe force that can result in adaptation!The force that can result in adaptation!Darwinian fitness – relative probability of Darwinian fitness – relative probability of survival and rate of reproduction of a survival and rate of reproduction of a phenotype or genotypephenotype or genotype Differential rates of survival and Differential rates of survival and

reproductionreproduction

Fitness is a consequence of the relation Fitness is a consequence of the relation between the phenotype of the organism between the phenotype of the organism and the environment in which it lives, so and the environment in which it lives, so the same genotype will have different the same genotype will have different fitnesses in different environmentsfitnesses in different environments consequence of relationship between consequence of relationship between

phenotype and environmentphenotype and environment same genotype may have different fitness in same genotype may have different fitness in

different environmentsdifferent environments

Heritability of beak depth in medium ground finches. The red line and circles are data from 1978, and the blue line and circles are from 1976 data. The results from the two years are consistent. Both show a strong relationship between the beak depth of parents and their offspring

In every natural population studied, more offspring are produced each generation than survive to breed. The reproductive capacity or biotic potential of organisms is astonishing (Table 3.1). It has been shown that in most populations, some individuals are more successful at mating and producing offspring than others. Variation in reproductive success represents an opportunity for selection, as does variation in survival.

Combining forces shape genetic Combining forces shape genetic structurestructure

Natural selection, mutation and genetic Natural selection, mutation and genetic drift all can combine to maintain allele drift all can combine to maintain allele frequenciesfrequencies

Populations undergo evolution, not Populations undergo evolution, not individualsindividuals

"Evolution is evidenced by changes in the "Evolution is evidenced by changes in the gene pool which includes all the genes of gene pool which includes all the genes of any population at any give time." any population at any give time."