A Summary of the Lecture Notes of Jeffrey R.

Chasnovs Population Genetics

Eduard C. Taganap

Chasnov suggested that population genetics can be defined as the mathematical modeling of the evolution and maintenance of polymorphism in a population. A population is said to have a polymorphism if a particular gene has more than one allele in the population. A gene is a particular DNA sequence that is the fundamental unit of heredity for a particular trait (Chasnov). Individuals are said to be diploid if they carry two copies of every gene which come from each parent. On the other hand, if they only carry one copy of gene they are said to be haploid. An allele is an alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome which is responsible in determining distinct traits that can be passed on from parents to offspring. An individual with two copies of the same allele is homozygous for the particular gene, while an individual carrying different alleles is heterozygous. Genotype is the combination of alleles carried by an individual while phenotype is the actual trait carried by an individual. Consider two alleles A and a of a gene which determines yellow-color seed and green-color seed of a pea plant respectively. In diploid genetics, a gene can appear with three distinct genotypes namely AA, Aa, and aa. For a particular gene, plants carrying AA and aa are homozygous while those who carry Aa are heterozygous. Plants with genotype AA will have a yellow-color seed while those with genotype aa will have a green-color seed. If the plants with genotype Aa will have a yellow-color seed then it can be concluded that allele A is dominant and allele a is recessive. Allele frequencies in a population can change due to four primary evolutionary forces: natural selection, mutation, genetic drift and migration. The focus of the discussion is to illustrate how to maintain genetic polymorphism in a population under natural selection and mutation. In the modeling process, it is assumed that the population size is infinite, the population is well mixed and the generation is discrete. The modeling is done in both haploid genetics and diploid genetics. HAPLOID GENETICS Assume two alleles A and a for a particular haploid gene which are carried in the population by nA and na individuals respectively. Assume further that a fraction of individuals carrying allele A (a) survives the reproduction stage and among those who survive contribute offspring to the next generation. Moreover, let nA(i) and na(i) represent the number of individuals carrying allele A and a in the ith generation respectively. Now formulating a discrete generation model for the individuals carrying allele A and a, we have and Table 1. Assumptions Needed in Formulating the Discrete Generation Model Genotype A a Number nA na Viability Fitness gA ga Fertility Fitness fA fa

Working with the numbers of individuals carrying allele A and a is more difficult to handle so it is better to operate with the allele frequencies. Thus, we let pi and qi be the frequency or the proportion of the individuals carrying allele A and a in the population in the ith generation respectively. Therefore Also note that . and . (1)

Now, taking the frequency of those that carry alleles A and a in the (i+1)th generation, we have and respectively.

Since From (1) Then ( )

then

( ( )

) ( )

But since

then

Thus

are the frequencies of individuals carrying alleles A and a respectively.

Note that from the equations of the evolution of allele frequencies, only the relative fitness matters. Thus, we consider only relative fitness and set one fitness to unity to simplify the algebra. Now under natural selection let us find when polymorphism will occur. And if it is, will it be stable or not? For the ease of notation let pi = p, pi+1 = p, qi = q , and qi+1 = q. Assuming that the fitness of survival of the individuals containing the allele A is greater than the fitness of survival of the individuals containing the allele a, then let the relative fitness of those individuals carrying allele a to be 1 and the relative fitness of those individuals carrying allele A to be . Table 2. Assumptions and Results Needed in Formulating the Discrete Generation Model under Natural Selection Genotype A a Frequency of gamete p q Relative fitness 1+s 1 Frequency after selection (1+s)p/w q/w Normalization w = (1+s)p+q

Thus using the derived frequency of the next generation

we have

But since q is dependent to p, we only need to focus on solving p.

Now let us consider when will be the frequency of individuals carrying allele A be fixed. To solve for the fixed points let and solve for p.

Fixed points are Now let us check the stability of the fixed foints. To solve for the stability, take by a theorem discussed in previous lessons is stable if . Then

and

If stable.

, but since s > 0 then . Thus is not

If

Since s > 0, 1< 1+s, thus Hence is stable.

The stability of states that there would be no polymorphism, that is there would be no possibility in the succeeding generations that an individual will still carry allele a when all individuals carry allele A. Now, if the selection coefficient s is small then

The Taylor Series expansion of denotes the higher order terms of s. Thus

under s then

where

Thus for s < < 1,

< < 1 then

can be approximated as

Note that (2) is a logistic growth equation which is stable at p = 1. Thus polymorphism for this gene exist in the population as the new allele spreads (allele a), but eventually A becomes fixed in the population and polymorphism is lost. Now consider two alleles, a wildtype allele A and a mutant allele a. Assume that the mutant allele a is a defective genotype which assigns a relative fitness of 1-s over the wildtype

allele A. Note that the relative fitness of an allele cannot be negative. Since the mutant allele a has a relative fitness 1-s over the wildtype allele A, then it can be assumed that s < 1. Now we determine the condition in which polymorphism can be achieved under the effect of natural selection and mutation. Since the wildtype allele has a greater relative fitness that the mutant allele, it can be said that natural selection favors allele A. Moreover, by allowing mutation, let u be the probability that an allele A be mutated to allele a. Then it can also be concluded that u < 1. The modeling process can be summarized using the table below. Table 3. Assumptions and Results Needed in Formulating the Discrete Generation Model under Natural Selection and Mutation Genotype A a Frequency of gamete p q Relative fitness 1 1-s Frequency after selection p/w (1-s)q/w Frequency after mutation (1-u)p/w ((1-s)q+up)/w normalization w = p+(1-s)q Note that the frequency of the individuals carrying allele A after selection is p/w. But it is further assumed that there is a probability u that allele A be mutated to allele a, then the frequency of those that has been mutated from allele A is up. up will be subtracted from the frequency of those that carry allele A and it will be added to the frequency of those carrying allele a. Frequency after natural selection can be derived using

which were derived earlier. Thus

But since q is dependent to p, we only need to solve for the fixed points of p. Let . Then

[ [ [

] ] ]

Thus the fixed points are

Now, let us check for the stability of the fixed points.

Let | | | For a fixed point to be stable, . | Note that s < 1 and u < 1, thus | Then | | | | |

Thus is stable if is no polymorphism. Now let |

. If this is the case, the population contains only allele a. Thus there

)|

| |

( ( | (

)| )| )|

| | | | |

A polymorphism is therefore possible under mutation-selection balance when s > u > 0.