Molecular Evolution and Population Genetics

Introduction to Population Genetics

• Definition of Populations: A population is a group of individuals belonging to the same species, inhabiting the same location, that can actually or potentially interbreed with each other, thereby sharing a common gene pool.

• Genetic Evolution Focus: The key to understanding genetic evolution lies in focusing on populations rather than individuals.

• Dynamic Nature of Populations: Populations are dynamic entities. Changes in their genetic structure are driven by factors such as:

  • Birth

  • Death

  • Migration

  • The merging of different populations

• Diversity: Populations are characterized as being more diverse than individuals.

Parameters of Population Genetics: Frequencies

There are three critical parameters to monitor within a population. A frequency always ranges between $0$ and $1$.

• Allele Frequency: This refers to the proportion of a specific allele at a given locus. It considers that a population may contain anywhere from one to many alleles at that specific locus.

  • Formula: $\text{Allele frequency} = \frac{\text{Number of copies of a specific allele in a population}}{\text{Total number of all types of alleles for that gene in a population}}$

• Genotype Frequency: This is the number of individuals possessing one particular genotype divided by the total number of individuals in the population.

  • Formula: $\text{Genotype frequency} = \frac{\text{Number of individuals with a particular genotype in a population}}{\text{Total number of individuals in a population}}$

• Phenotype Frequency: The proportion of individuals in a population that exhibit a given phenotype.

Theoretical and Practical Frequency Calculations

General Example (AA, Aa, aa genotypes)

• Suppose genotypes are AA, Aa, and aa.

• Frequency of genotypes: $AA = 0.49$, $Aa = 0.42$ (composed of $0.21 + 0.21$), and $aa = 0.09$.

• Frequency of alleles in gametes:

  • Allele $A = 0.49 + 0.21 = 0.7$

  • Allele $a = 0.21 + 0.09 = 0.3$

Hypothetical Frog Population Example

For a population with these genotypes: $100\,GG$, $160\,Gg$, and $140\,gg$. Total individuals = $400$. Total alleles = $800$.

• Genotype Frequencies:

  • $GG = \frac{100}{400} = 0.25$

  • $Gg = \frac{160}{400} = 0.40$

  • $gg = \frac{140}{400} = 0.35$

• Phenotype Frequencies:

  • Green Phenotype ($GG + Gg$): $100 + 160 = 260$. Frequency: $\frac{260}{400} = 0.65$

  • Brown Phenotype ($gg$): $140$. Frequency: $\frac{140}{400} = 0.35$

• Allele Frequencies:

  • Allele $G$: $\frac{(100 \times 2) + 160}{800} = \frac{360}{800} = 0.45$

  • Allele $g$: $\frac{(140 \times 2) + 160}{800} = \frac{440}{800} = 0.55$

• Alternative Calculation for Allele Frequencies:

  • $\text{Freq}(G) = [0.25 + \frac{0.40}{2}] = 0.45$

  • $\text{Freq}(g) = [0.35 + \frac{0.40}{2}] = 0.55$

The Gene Pool

• Definition: The total aggregate of genes in a population at any given time.

• Fixation: If every member of a population is homozygous for the same allele, that allele is categorized as fixed.

• Relative Frequency: Genes often have two or more alleles; for example, Human Blood Types involve A, B, AB, and O alleles.

• Evolutionary Change: Allele frequencies may change between generations. Short-term shifts cause changes in phenotype frequency, while long-term change in allele frequency constitutes evolutionary change.

The Hardy-Weinberg Law (HWE)

The Hardy-Weinberg Law measures allele and genotype frequencies and states that they remain constant from generation to generation given certain assumptions are met.

Assumptions for Genetic Equilibrium

1. Large Population Size: Prevents chance fluctuations (sampling error) in allele frequencies caused by events like storms or fires.

2. No Migration: Immigrants can introduce new alleles, changing the existing frequency.

3. No Net Mutations: Stops alleles from changing from one type to another.

4. Random Mating: Prevents selected traits from being favored, which would stop the random mixing of alleles.

5. No Natural Selection: Ensures survival and reproduction rates are equal across individuals so that specific genes aren't favored in the next generation.

The Hardy-Weinberg Equations

For a gene in a diploid species with only two alleles (A and a, or G and g):

• Allele frequency equation: $p + q = 1$

• Genotype frequency equation: $p^2 + 2pq + q^2 = 1$

• Key:

  • $p$ = frequency of the dominant allele (A)

  • $q$ = frequency of the recessive allele (a)

  • $p^2$ = frequency of the homozygous dominant genotype (AA)

  • $2pq$ = frequency of the heterozygous genotype (Aa)

  • $q^2$ = frequency of the homozygous recessive genotype (aa)

Application Case Study: Wildflowers

• Population size: $500$ plants.

• White flowers (rr): $20$ individuals ($q^2$).

• Red flowers (RR or Rr): $480$ individuals.

• Breakdown: $320\,RR$ and $160\,Rr$.

• Calculations:

  • Total allele copies: $500 \times 2 = 1,000$.

  • Count for R: $(320 \times 2) + 160 = 800$.

  • $p = \frac{800}{1000} = 0.8$ (80%).

  • $q = 1 - 0.8 = 0.2$ (20%).

Applications in Human Genetics

• Autosomal Traits: Count individuals with recessive phenotypes ($q^2$), find $q = \sqrt{q^2}$, then calculate $p = 1 - q$.

• X-Linked Traits:

  • Females (XX) carry $\frac{2}{3}$ of alleles; males (XY) carry $\frac{1}{3}$.

  • In males, the frequency of the mutant phenotype equals the allele frequency ($q$).

  • In females, the frequency of the trait is $q^2$.

• Multiple Alleles (ABO Blood Group):

  • Allele frequencies: $p(A) + q(B) + r(O) = 1$.

  • Genotype expansion: $(p+q+r)^2 = p^2(AA) + 2pq(AB) + 2pr(AO) + q^2(BB) + 2qr(BO) + r^2(OO) = 1$.

Microevolution

• Definition: Evolution within a single species or population. It refers to gradual changes in allele frequencies in a gene pool from one generation to the next.

Causes of Microevolution

1. Genetic Drift: Change in the gene pool of a small population due to chance events unrelated to fitness. Changes occur due to random sampling error. It favors either the total loss ($0\%$) or fixation ($100\%$) of an allele.

   • Bottleneck Effect: A sudden decrease in population size due to disasters (e.g., The Black Plague in the 1340s eliminated up to 75% of some European populations). Results in a surviving gene pool that differs from the original. Example: Cheetahs.

   • Founder Effect: Genetic drift occurring when a small population colonizes a new area (common on islands). Genetic variation is reduced, and allele frequencies differ from the parent population.

2. Natural Selection: Success in reproduction based on heritable traits. Selects alleles that provide an adaptation to the environment.

3. Gene Flow: Genetic exchange due to migration (immigration and emigration) of fertile individuals or gametes. It reduces differences between populations but enhances diversity within a single population.

4. Mutation: A change in DNA. While rare at an individual locus, mutations are the ultimate source of genetic variation. Cumulative impacts across thousands of loci and individuals are significant.

5. Non-random Mating: Mates chosen based on specific traits.

   • Assortative: Similar phenotypes mate; increases homozygosity.

   • Disassortative: Dissimilar phenotypes mate; favors heterozygosity.

   • Inbreeding: Choice based on genetic history. Increases homozygosity but may lower mean fitness (inbreeding depression) if homozygous offspring are less fit.

Natural Selection and Fitness

• Modern Description: Beneficial alleles are more likely to be passed on. Over generations, this alters population characteristics, making them better adapted to the environment or more successful at reproduction (e.g., Sickle cell anemia in West Africa).

• Fitness: The ability of an individual to survive and reproduce. It is essentially the lifetime reproductive success. It is not physical performance.

  • Genotype Fitness: Average fitness of all individuals with that genotype.

• Darwinian Fitness (W): The relative likelihood that a genotype contributes to the gene pool of the next generation compared to other genotypes. The maximum value for the most successful genotype is $1.0$.

  • Example: If AA produces 5 offspring, Aa produces 4, and aa produces 1:

    • $W_{AA} = \frac{5}{5} = 1.0$

    • $W_{Aa} = \frac{4}{5} = 0.8$

    • $W_{aa} = \frac{1}{5} = 0.2$

• Survival of the Fittest: Survival alone does not guarantee success. A highly fit individual who is sterile has a Darwinian fitness of zero.

Patterns of Selection

1. Stabilizing Selection: Favors intermediate phenotypes (the mean) and selects against extremes. Usually occurs in stable environments.

   • Example: Clutch Size in birds. Too many eggs result in death due to lack of care/food; too few eggs do not contribute enough to the next generation.

2. Directional Selection: Favors individuals at one extreme of the phenotypic distribution. Initiated by new mutations or prolonged environmental change.

   • Example: Dark brown fur mutation in mice. If dark fur reduces predation, the dark mouse has higher Darwinian fitness, eventually shifting the population mean.

3. Disruptive (Diversifying) Selection: Favors two or more genotypes that produce different phenotypes. Likely in diverse environments where members can still interbreed.

   • Example: Agrostis tenuis (Bent grass). Plants on contaminated soil carry metal-resistant alleles; those on uncontaminated soil do not.

4. Balancing Selection: Maintains genetic diversity via balanced polymorphism.

   • Heterozygote Advantage: The heterozygote is favored (e.g., HS allele for Sickle Cell providing resistance to Malaria).

   • Negative Frequency-Dependent Selection: Rare individuals have higher fitness.

Sexual Selection

Natural selection directed at traits that improve the likelihood of finding a mate or successful mating. It may often explain traits that decrease survival but increase reproductive success.

• Intrasexual Selection: Competition between members of the same sex (e.g., horns in male sheep, antlers in moose, enlarged claws in male fiddler crabs).

• Intersexual Selection: Choice between members of the opposite sex (Female choice). Results in showy male characteristics.

  • Cryptic Female Choice: The female genital tract or egg selects against genetically related sperm to inhibit inbreeding.

• Case Study: Male Guppies (Poecilia reticulata): In areas with few predators, females prefer brightly colored males. In high-predation areas, duller colored males are plentiful as they escape predation. The population reflects a balance between sexual selection (bright) and survival (dull).