👨‍👩‍👦‍👦General Genetics Unit 16 – Population and Evolutionary Genetics

Key Concepts in Population Genetics

• Population genetics studies the genetic composition of populations and how it changes over time
• Allele frequency represents the proportion of a specific allele at a given locus within a population
• Genotype frequency describes the proportion of individuals with a specific genotype in a population
• Hardy-Weinberg equilibrium assumes that allele and genotype frequencies remain constant from generation to generation in the absence of evolutionary forces
• Evolutionary forces such as mutation, natural selection, genetic drift, and gene flow can alter allele frequencies within populations
• Effective population size ($N_e$) represents the number of individuals in an idealized population that would experience the same amount of genetic drift as the actual population
• Coalescent theory traces alleles back in time to their most recent common ancestor (MRCA) to infer population history and demographics

Genetic Variation and Its Sources

• Genetic variation arises from differences in DNA sequences among individuals within a population
• Mutations introduce new alleles into a population and serve as the ultimate source of genetic variation
  • Point mutations involve single nucleotide changes (substitutions, insertions, or deletions)
  • Chromosomal mutations affect larger segments of DNA (duplications, deletions, inversions, or translocations)
• Recombination during meiosis shuffles alleles between maternal and paternal chromosomes, creating new combinations of alleles
• Sexual reproduction generates unique genotypes by combining alleles from two parents
• Standing genetic variation refers to the existing allelic diversity within a population at a given time
• Balancing selection maintains multiple alleles at a locus in a population (heterozygote advantage, frequency-dependent selection)
• Transposable elements (transposons) can create genetic variation by inserting themselves into new locations within the genome

Hardy-Weinberg Equilibrium

• Hardy-Weinberg equilibrium (HWE) describes a population in which allele and genotype frequencies remain constant across generations
• Assumptions of HWE include random mating, no mutation, no selection, no migration, and an infinitely large population size
• The Hardy-Weinberg equation ($p^2 + 2pq + q^2 = 1$) calculates expected genotype frequencies based on allele frequencies
  • $p$ represents the frequency of the dominant allele, and $q$ represents the frequency of the recessive allele
• Deviations from HWE can indicate the presence of evolutionary forces acting on the population
• Chi-square ($\chi^2$) goodness-of-fit test compares observed genotype frequencies to those expected under HWE to detect deviations
• HWE serves as a null model for population genetics, providing a baseline to identify and measure evolutionary processes

Factors Affecting Allele Frequencies

• Mutation introduces new alleles into a population and is the ultimate source of genetic variation
• Natural selection favors the reproduction of individuals with advantageous traits, leading to changes in allele frequencies over time
  • Directional selection shifts the mean phenotype in a particular direction (antibiotic resistance)
  • Stabilizing selection favors intermediate phenotypes and reduces variation (birth weight)
  • Disruptive selection favors extreme phenotypes over intermediate ones (beak size in finches)
• Genetic drift causes random fluctuations in allele frequencies, particularly in small populations
  • Bottleneck effect occurs when a population undergoes a drastic reduction in size, leading to a loss of genetic diversity (cheetahs)
  • Founder effect arises when a small number of individuals establish a new population, resulting in reduced genetic variation (Amish)
• Gene flow is the transfer of alleles between populations through migration or interbreeding
  • Admixture occurs when two previously isolated populations interbreed, resulting in the exchange of alleles (African Americans)
• Non-random mating, such as inbreeding or assortative mating, can alter genotype frequencies within a population

Natural Selection and Adaptation

• Natural selection is the differential survival and reproduction of individuals due to differences in phenotype
• Fitness describes an individual's ability to survive and reproduce in a given environment
• Adaptation refers to the process by which populations become better suited to their environment through natural selection
• Directional selection leads to a shift in the mean phenotype of a population over time (beak size in Galápagos finches)
• Stabilizing selection favors intermediate phenotypes and reduces variation (human birth weight)
• Disruptive selection favors extreme phenotypes over intermediate ones (color polymorphism in peppered moths)
• Sexual selection arises from differential mating success and can lead to the evolution of exaggerated traits (peacock tail)
• Balancing selection maintains multiple alleles at a locus in a population (sickle cell anemia and malaria resistance)

Genetic Drift and Gene Flow

• Genetic drift is the random fluctuation of allele frequencies due to chance events, particularly in small populations
• Bottleneck effect occurs when a population undergoes a drastic reduction in size, leading to a loss of genetic diversity (northern elephant seals)
• Founder effect arises when a small number of individuals establish a new population, resulting in reduced genetic variation (Amish populations)
• Effective population size ($N_e$) represents the number of individuals in an idealized population that would experience the same amount of genetic drift as the actual population
• Gene flow is the transfer of alleles between populations through migration or interbreeding
• Admixture occurs when two previously isolated populations interbreed, resulting in the exchange of alleles (Latino populations)
• Isolation by distance describes the pattern of decreased genetic similarity with increasing geographic distance between populations
• Fst ($F_{ST}$) is a measure of population differentiation based on genetic variation within and between populations

Molecular Evolution and Phylogenetics

• Molecular evolution studies the evolution of DNA sequences and proteins over time
• Mutations accumulate in DNA sequences at a relatively constant rate, allowing for the estimation of divergence times between species (molecular clock)
• Synonymous mutations do not change the amino acid sequence of a protein, while nonsynonymous mutations do
• dN/dS ratio compares the rate of nonsynonymous to synonymous substitutions and can indicate the presence of selection
• Phylogenetics is the study of evolutionary relationships among organisms based on genetic or morphological data
• Phylogenetic trees represent the evolutionary history and relationships among taxa (species, populations, or genes)
  • Branches represent evolutionary lineages, and nodes represent common ancestors
• Maximum parsimony, maximum likelihood, and Bayesian inference are common methods for constructing phylogenetic trees
• Horizontal gene transfer (HGT) is the transfer of genetic material between organisms other than through vertical inheritance (antibiotic resistance in bacteria)

Applications and Case Studies

• Population genetics principles are applied in conservation biology to manage endangered species and maintain genetic diversity (Florida panther)
• Genetic testing and counseling rely on understanding the inheritance patterns of genetic disorders (Huntington's disease)
• Forensic genetics uses genetic markers to identify individuals or establish familial relationships in legal cases (paternity testing)
• Ancient DNA analysis provides insights into the evolutionary history and demographics of extinct species or populations (Neanderthals)
• Genome-wide association studies (GWAS) identify genetic variants associated with complex traits or diseases (type 2 diabetes)
• Selective breeding and marker-assisted selection in agriculture and animal husbandry rely on understanding the genetic basis of desired traits (drought-resistant crops)
• Phylogenetic analysis is used in epidemiology to track the spread and evolution of pathogens (influenza virus)
• Comparative genomics explores the similarities and differences among genomes of different species to understand evolutionary processes (human-chimpanzee comparison)