Genetics: Analysis and Principles Robert J. Brooker CHAPTER 24 POPULATION GENETICS

INTRODUCTION The central issue in population genetics is genetic variation –Its extent within populations –Why it exists –How it changes over the course of many generations Population genetics emerged as a branch of genetics in the 1920s and 1930s –Its foundations are largely attributed to 3 mathematicians Sir Ronald Fisher, Sewall Wright, and J. B. S. Haldane

GENES IN POPULATIONS Population genetics it is a direct extension of our understanding of Mendel’s laws of inheritance, molecular genetics, and the ideas of Darwin. The focus shifts away from the individual and toward the population of which the individual is a member. Conceptually, all of the alleles of every gene in a population make up the gene pool. Population geneticists study the genetic variation within the gene pool and how it changes from one generation to the next

What is a Population? A population is a group of individuals of the same species that occupy the same region and can interbreed with each other A large population is usually composed of smaller groups called local populations –These are also called demes –Members of a local population are far likelier to breed with each other than with members of the general population –Local populations are often separated from each other by moderate geographic barriers

What is a Population? Populations typically are dynamic units that change from one generation to the next –A population may change in Size Geographic location Genetic composition Population geneticists have developed mathematical theories that predict how the gene pool will change in response to fluctuations in the above

Some Genes Are Monomorphic, but Most Are Polymorphic The term polymorphism refers to the observation that many traits display variation within a population Figure 24.2 illustrates a striking example of polymorphism in the Hawaiian happy-face spider –All individuals are from the same species, Theridion grallator But they differ in alleles that affect color and pattern

–In other words, it is due to genetic variation At the DNA level, polymorphism is due to two or more alleles that influence the phenotype –In other words, it is due to genetic variation Polymorphic is also used to describe a gene that commonly exists as 2 or more alleles in a population A monomorphic gene exists predominantly as a single allele By convention, when a single allele is found in at least 99% of all cases, the gene is considered monomorphic Variation can be even a single-nucleotide polymorphism (SNP) These account for 90% of variation between people

Allelic and Genotypic Frequencies Allele frequency = Total number of all alleles for that gene in a population Number of copies of an allele in a population Genotype frequency = Total number of all individuals in a population Number of individuals with a particular genotype in a population

Allele Frequency Consider a population of 100 frogs 64 dark green (genotype GG) 32 medium green (genotype Gg) 4 light green (genotype gg) 100 total frogs Total number of alleles in the population Number of copies of allele g in the population Frequency of allele g = Homozygotes have two copies of allele g Heterozygotes have only one (2)(4) + 32 Frequency of allele g = (2)(100) All individuals have two alleles of each gene 200 40 Frequency of allele g = = 0.2, or 20% Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

Genotype Frequency (frequency of individuals with particular genotype) Consider a population of 100 frogs 64 dark green (genotype GG) 32 medium green (genotype Gg) 4 light green (genotype gg) 100 total frogs Frequency of genotype gg = Total number of all individuals in the population Number of individuals with genotype gg in the population 100 4 Frequency of genotype gg = = 0.04, or 4%

More on allele and genotype frequencies For each gene, allele and genotype frequencies are always < 1 (less than or equal to 100%) Monomorphic genes (only one allele) Allele frequency = 1.0 (or very close to 1) Polymorphic genes Frequencies of all alleles  add up to 1.0 Pea plant example Frequency of G + frequency of g = 1 Frequency of G = 1 – frequency of g = 1 – 0.2 = 0.8, or 80%

Mathematical relationship between alleles and genotypes

Mathematical relationship between alleles and genotypes is described by the Hardy-Weinberg Equation (HWE) For any one gene, HWE predicts the expected frequencies for alleles and genotypes (population must be in equilibrium) Example: Polymorphic gene exists in two alleles, G and g Population frequency of G is denoted by variable p Population frequency of g is denoted by variable q By definition p + q = 1.0 The Hardy-Weinberg equation states: (p + q)2 = 1 p2 + 2pq + q2 = 1 X-axis in Fig 24.5

What is a population in equilibrium? (the one in Fig 24.5) When the genotype and allele frequencies remain stable, generation after generation (when the relationship between the two remains “true”) A population can be in equilibrium only if certain conditions exist: 1. No new mutations 2. No genetic drift (population is so large that allele frequencies do not change due to random sampling between generations) 3. No migration 4. No natural selection 5. Random mating In reality, no population satisfies the Hardy-Weinberg equilibrium completely However, in some large natural populations there is little migration and negligible natural selection HW equilibrium is nearly approximated for certain genes

Hardy-Weinberg Equation To determine if the genes or genotypes of a population are not changing, the expected frequencies of the different genotypes can be calculated and compared to what is observed If p = 0.8 and q = 0.2, then the expected frequencies of the different genotypes in a population that is not changing can be determined frequency of GG = p2 = (0.8)2 = 0.64 frequency of Gg= 2pq = 2(0.8)(0.2) = 0.32 frequency of gg = q2 = (0.2)2 = 0.04

Why bother with Hardy-Weinberg Equation? HWE provides a null hypothesis against which we can test many theories of evolution (provides a framework to help understand when allele and genotype frequencies do* change) HW equation can extend to 3 or more alleles

Example of using X2 analysis to see if a gene is in HWE Consider a human blood type called the MN type (two co-dominant alleles, M and N) An Inuit population in East Greenland has 200 people 168 were MM 30 were MN 2 were NN 200 total

Mechanisms that alter existing genetic variation Natural Selection Random genetic drift Migration Nonrandom mating

Mechanisms that alter existing genetic variation Natural Selection Directional Selection Stabilizing Selection Disruptive Selection Balancing Selection Random genetic drift Migration Nonrandom mating

Natural selection works via mating efficiency, fertility, and reproductive success Variants that are best-adapted to that environment will continue to survive and reproduce, rising in frequency Struggle and competition for existence Environment selects families (and the alleles they carry) that best reproduce in that environment Allelic variation in population; some alleles enhance individual’s reproductive capacity Population is better adapted to its environment and/or more successful at reproduction

Darwinian fitness--a measure of reproductive superiority Not to be confused with physical fitness Fitness = relative likelihood that a phenotype will survive and contribute to the gene pool of the next generation Consider a gene with two alleles: A and a The three genotypic classes can be assigned fitness values according to their reproductive potential

Assigning relative fitness (W) Suppose the average reproductive success is AA  5 offspring Aa  4 offspring aa  1 offspring The allele with the highest reproductive ability has a fitness value = 1.0 The fitness values of the other genotypes are assigned relative to 1 Fitness values (W) Fitness of AA: WAA = 5/5 = 1.0 Fitness of Aa: WAa = 4/5 = 0.8 Fitness of aa: Waa = 1/5 = 0.2

How differing fitness values change HW Equilibrium For our hypothetical gene: The three fitness values are WAA = 1.0 WAa = 0.8 Waa = 0.2 In the next generation, the HW equilibrium will be modified in the following way by directional selection: Frequency of AA: (p2) (WAA ) Frequency of Aa: (2pq) (WAa ) Frequency of aa: (q2) (Waa) (when HW equilibrium does exists, there is “no natural selection” and the fitness values of AA, Aa, and aa are all the same or equal to one)

What happens when a population is changing due to natural selection? The three terms may not add up to 1.0, as they would in the HW equilibrium Instead, they sum to a value known as the mean fitness of the population: If both sides of the equation are divided by the mean fitness of the population, the expected genotype and allele frequencies after one generation of natural selection can be calculated

As an example, let’s suppose that the starting allele frequencies are A = 0.5 and a = 0.5, and use fitness values of 1.0, 0.8, and 0.2 for the three genotypes, AA, Aa, and aa, respectively. We begin by calculating the mean fitness of the population:

Natural selection raises the mean fitness of the population The mean fitness of the population has increased from 0.7 to 0.8. Using the same process, we can find all the values for the subsequent generation f(A) will increase to 0.85 f(a) will decrease to 0.15 The mean fitness of the population increases to 0.931 If an allele is introduced or arises by mutation that results in an increased fitness for those individuals that carry that allele, it can become monomorphic

Natural selection may occur in several ways 1. Directional selection - favors survival of one extreme phenotype that is better adapted to an environmental condition 2. Stabilizing selection - favors the survival of individuals with intermediate phenotypes 3. Disruptive (or diversifying) selection - favors the survival of two (or more) different phenotypes 4. Balancing - favors the maintenance of two or more alleles

Directional Selection Dark brown coloration arises by a new mutation. Dark brown wings make the butterflies less susceptible to predation. The dark brown butterflies have a higher Darwinian fitness than do the light butterflies. Many generations This population has a higher mean fitness than the starting population because the darker butterflies are less susceptible to predation and therefore are more likely to survive and reproduce. Affects the Hardy-Weinberg equilibrium and allele frequencies by favoring the extreme phenotype If the homozygote carrying the favored allele has the highest fitness value then it may become monomorphic.

Directional selection from the introduction of DDT for mosquitos The resistance of mosquitoes to the insecticide DDT was a relatively rare phenotype With DDT as a selection pressure, the alleles that allowed for resistance to DDT became more frequent.

Stabilizing Selection Stabilizing selection - extreme phenotypes are selected against and the intermediate phenotypes have the highest fitness values Tends to decrease genetic diversity for a particular gene Eliminates those alleles that cause variation E.g. Laying eggs Too many eggs drains resources to care for young Too few eggs does not contribute to next generation

Disruptive Selection Also known as diversifying selection Disruptive selection favors the survival of two or more different genotypes with different phenotypes Also known as diversifying selection Caused by fitness values for a given genotype that vary in different environments

Example -- snail that lives in woods and open fields brown shell color favored in woods with open soil pink shell color favored in woods with leaf litter yellow shell cover favored in sunny, grassy areas Migration maintains balance of polymorphisms

Balancing Selection A polymorphism may reach an equilibrium where opposing selective forces balance each other The population is not evolving toward allele fixation or elimination Such a situation is known as balancing selection It can occur because of different reasons 1. The heterozygote is at a selective advantage 2. A species occupies a region that contains heterogeneous environments The heterozygote is at a selective advantage The higher fitness of the heterozygote is balanced by the lower fitness of both corresponding homozygotes

Balanced polymorphisms can sometimes explain the high frequency of alleles that are deleterious when homozygous Cystic fibrosis Heterozygote is resistant to diarrheal disease (such as cholera) Tay-Sachs disease Heterozygote is resistant to tuberculosis Sickle cell anemia Heterozygotes have a better chance of survival if infected by the malarial parasite Plasmodium falciparum

Genetic Drift Random genetic drift refers to random (i.e. not affected by selection) changes in allele frequencies due to chance fluctuations Sewall Wright played a key role in developing this concept in the 1930s In other words, allele frequencies may drift from generation to generation as a matter of chance Over the long run, genetic drift favors either the loss or the fixation of an allele The rate depends on the population size

Bottleneck Effect Figure 24.17

Relative Genetic Diversities in human populations implicate multiple bottlenecking events due to migration and expansion