Population Genetics: Forces Shaping Genetic Variation

Population Genetics: Forces Shaping Genetic Variation

Four Forces That Shape the Gene Pool

Population genetics studies how genetic variation is shaped and maintained within populations. Four primary evolutionary forces influence the gene pool:

• Mutation: Introduces new alleles, increasing genetic variation.

• Genetic Drift: Random changes in allele frequencies, often reducing genetic variation, especially in small populations. Can lead to allele fixation or loss.

• Selection: Alters genetic variation depending on type:

  • Directional selection: Reduces variation by favoring one allele.

  • Balancing selection: Maintains variation by favoring heterozygotes or multiple alleles.

• Migration (Gene Flow): Increases variation within populations by introducing new alleles, but reduces differences between populations.

Hardy-Weinberg Equilibrium (HWE)

The Hardy-Weinberg Equilibrium describes the expected genotype frequencies in a non-evolving population (no mutation, migration, drift, or selection, and random mating):

$p^2 + 2pq + q^2 = 1$

• p: Frequency of the dominant allele (A)

• q: Frequency of the recessive allele (a)

• p^2: Frequency of homozygous dominant (AA)

• 2pq: Frequency of heterozygotes (Aa)

• q^2: Frequency of homozygous recessive (aa)

Allele frequencies must sum to:

$p + q = 1$

Deterministic vs. Stochastic Models

Modeling Biological Processes

• Deterministic Models: Make exact predictions; use fixed parameter values.

• Stochastic Models: Incorporate random chance; predict a range of outcomes rather than a single value.

Reductionist Approach in Biology

A reductionist approach simplifies complex systems by analyzing one factor at a time under controlled conditions. This helps in understanding the effect of each variable.

1. Start with a basic system (e.g., single gene under selection).

2. Gradually relax assumptions.

3. Observe how changes affect outcomes.

Fitness and Selection

Relative Fitness

Relative fitness is the ability of different genotypes to pass on their alleles to future generations, compared to other genotypes.

Fitness Array

A fitness array lists the relative probability of survival for each genotype. The mean fitness of a population is the sum of the relative contributions of all genotypes.

Selection Coefficient (s)

The selection coefficient ($s$) measures the amount of selection against a genotype, typically ranging from 0 to 1.

Environmental Context and Fitness

Fitness values depend on environmental conditions. For example:

• With warfarin exposure, heterozygotes (RS) have the highest fitness (balanced polymorphism).

• Without warfarin, SS homozygotes are more fit and the R allele decreases.

Types of Selection

• Positive Selection: Favors a beneficial allele.

• Purifying Selection: Removes harmful alleles; stabilizing selection favors intermediate trait values.

• Balancing Selection: Maintains genetic variation (e.g., heterozygote advantage).

• Disruptive Selection: Favors individuals with extreme trait values.

Persistence of Deleterious Alleles

Deleterious alleles persist in populations due to mechanisms like heterozygote advantage or balancing selection. As their frequency decreases, the rate of change slows, causing the graph to plateau.

Allele Frequency Changes Over Generations

• Alleles that increase fitness rise in frequency.

• Deleterious alleles decline unless maintained by balancing selection.

Mean Fitness ($\bar{w}$)

Mean fitness is the average reproductive success of all genotypes in a population, weighted by their frequencies.

Equilibrium and Frequency-Dependent Selection

Stable vs. Unstable Equilibrium

• Heterozygote Advantage (Overdominance): Heterozygotes have higher fitness than either homozygote, maintaining both alleles in the population (stable equilibrium).

• Heterozygote Disadvantage (Underdominance): Heterozygotes have lower fitness, leading to fixation of one allele (unstable equilibrium).

Frequency-Dependent Selection

Fitness of a genotype depends on its frequency in the population. Rare alleles may have a fitness advantage, but as they become common, their advantage decreases.

Example: Scale-Eating Cichlids (Perissodus microlepis)

• Found in Lake Tanganyika.

• Fish attack prey from left or right, with jaw asymmetry.

• Frequency-dependent selection maintains both jaw types in the population.

Mutation: Types and Effects

Spontaneous vs. Induced Mutation

• Spontaneous: Occur naturally, e.g., errors during DNA replication.

• Induced: Caused by environmental factors (chemicals, radiation).

Common Sources of Spontaneous Mutations

• Replication error

• Spontaneous lesion

• Transposition

Synonymous vs. Nonsynonymous Mutations

• Nonsynonymous Mutation (dN): Changes amino acid sequence, may affect protein function.

• Synonymous Mutation (dS): Does not change amino acid sequence, usually neutral.

dN/dS Ratio

The dN/dS ratio is used to identify genes under selection:

• $dN/dS < 1$: Purifying selection

• $dN/dS > 1$: Positive selection

Forward vs. Reverse Mutation

• Forward mutation (a): Wild type to detrimental allele.

• Reverse mutation (r): Detrimental allele back to wild type.

• Generally, forward mutation rates are higher than reverse.

Mutation-Selection Balance

For a recessive, deleterious allele, equilibrium frequency ($q_e$) depends on:

1. The mutation rate ($\mu$) introducing the allele.

2. The selection coefficient ($s$) removing it.

Example: Spinal Muscular Atrophy vs. Cystic Fibrosis

• Spinal Muscular Atrophy (SMA): Maintained by mutation-selection balance; observed mutation rates match predictions.

• Cystic Fibrosis (CF): Not maintained by mutation-selection balance; mutation rate is too low.

Genetic Drift

Bottleneck Effect

Occurs when a population is drastically reduced in size, leading to loss of genetic variation. Example: Pingelap Island population descended from 20 survivors, resulting in high frequency of achromatopsia.

Founder Effect

When a small group establishes a new population, only a fraction of the genetic variation from the source population is present, leading to sampling error.

Drift and Gene Pool

• Drift causes genetic divergence between isolated populations.

• Increases genetic variation between populations, decreases within populations.

Population Size and Drift

• Drift is stronger in small populations; allele frequencies fluctuate more widely.

• In large populations, allele frequencies remain relatively stable.

Buri's Experiment (1956)

Studied genetic drift in Drosophila using 107 replicate populations:

• Each started with 8 males and 8 females for the bw75 allele ($q = 0.5$).

• Over time, populations drifted toward fixation or loss of the allele.

• Variation between populations increased; average allele frequency stayed ~0.5.

• Heterozygosity decreased steadily, showing drift reduces variation without selection.

Drift and Heterozygosity

Drift reduces heterozygosity within populations as alleles are randomly fixed or lost. Smaller populations lose heterozygosity faster.

Equilibrium in Population Genetics

Definition of Equilibrium

• Point at which there is no change in allele frequency due to mutation.

• Determined by the rate of forward ($a$) and reverse ($r$) mutations.

• At this point, Hardy-Weinberg Equilibrium takes over.

Summary Table: Forces Affecting Genetic Variation

Force	Effect on Variation	Example
Mutation	Increases	New alleles from replication errors
Genetic Drift	Decreases (within); Increases (between)	Bottleneck effect in Pingelap Island
Selection	Can increase or decrease	Directional selection for beneficial allele
Migration	Increases (within); Decreases (between)	Gene flow between populations

Additional info:

• These notes are suitable for introductory and intermediate college-level population genetics, a subfield of genetics and evolutionary biology. They do not cover organic chemistry topics.