Population Genetics: Principles, Factors, and Applications

Population Genetics

Introduction to Population Genetics

Population genetics is the study of genetic variation within populations and involves the examination of allele frequency distribution and change under the influence of evolutionary processes. It is fundamental for understanding why certain genetic diseases are more common in specific populations and how genetic traits are inherited and maintained.

• Key Concepts: Genotype, allele frequency, Hardy-Weinberg equilibrium

• Applications: Genetics in medicine, disease prevalence, evolutionary biology

Hardy-Weinberg Equilibrium

The Hardy-Weinberg equilibrium describes a theoretical state in which allele and genotype frequencies in a population remain constant from generation to generation, provided that certain conditions are met.

• Conditions Required:

  • Random mating

  • Infinitely large population

  • No mutation

  • No migration (no gene flow)

  • No selection (all genotypes have equal fitness)

  • Organisms are diploid

  • Allele frequencies are equal in both sexes

• Equation:

  • $p^2 + 2pq + q^2 = 1$

  • Where $p$ and $q$ are the frequencies of two alleles at a locus

• Significance: Deviations from equilibrium indicate evolutionary forces at work

Factors Affecting Hardy-Weinberg Equilibrium

Several factors can disrupt Hardy-Weinberg equilibrium, leading to changes in allele frequencies over time.

• Stratification

• Assortative mating

• Consanguinity

• Mutations and selection (fitness)

• Gene flow and migration

• Genetic drift (bottleneck, founder effect)

Non-Random Mating

Stratification

Stratification occurs when a population contains subgroups that remain relatively genetically separate due to factors such as wealth, ethnicity, religion, or social class. This can lead to different frequencies of genetic diseases in subgroups.

• Examples: Orthodox Jews, Sunni and Shia Muslims, French-speaking Canadians, Castes in India, US population stratified by ethnicity or religion

• Effect: Higher frequency of homozygotes for certain alleles in subgroups

Assortative Mating

Assortative mating is the tendency for individuals to mate with others who are similar (positive assortative mating) or dissimilar (negative assortative mating) in certain traits.

• Positive Assortative Mating: Mating with individuals who share similar traits (e.g., physical appearance, education, language, medical conditions)

• Negative Assortative Mating: Mating with individuals who are different in certain traits (e.g., tall people marrying short people, individuals from different religions)

• Effect: Can increase or decrease genetic variation depending on the type

Consanguinity

Consanguinity refers to mating between individuals who are related as second cousins or closer. This increases the frequency of homozygous genotypes and the risk of autosomal recessive diseases.

• Definition: Union between two individuals who are related as second cousins or closer

• Effect: Increased frequency of autosomal recessive diseases, higher homozygosity

• Examples: Royal families, small isolated communities

Mutations and Selection

Fitness of Mutations

Mutations can be classified as beneficial, harmful, or neutral. Beneficial mutations increase the fitness of individuals, while harmful mutations decrease it.

• Fitness: The ability of an individual to survive and reproduce

• Selection: The process by which certain alleles increase in frequency due to their effect on fitness

Types of Natural Selection

Model	AA	Aa	aa	Type of Selection
Case I	X	X		Against Dominant Phenotype
Case II		X	X	Against Recessive Phenotype
Case III	X		X	Against Both Homozygotes; Heterozygote Has Highest Fitness

Selection Against Autosomal Dominant Mutations

• Dominant mutant alleles are exposed to selection

• Affected individuals often do not reproduce

• Example: Osteogenesis Imperfecta Type 2 (lethal after birth)

Selection Against Autosomal Recessive Mutations

• Mutant alleles present in both homozygotes and heterozygotes

• Homozygotes are exposed to selection, but heterozygotes may carry the allele without being affected

• Example: Phenylketonuria (PKU)

Selection for Heterozygotes (Heterozygote Advantage)

• Heterozygotes may have increased fitness compared to both homozygotes

• Example: Sickle cell trait confers resistance to malaria

Genotype	Observed Frequency Among Adults	Expected in HW Equilibrium
SS (Disease)	29	187
S/A (Trait)	2398	2673
A/A (Normal)	9960	9527
Total	12,387	12,387

Gene Flow and Migration

Migration & Gene Flow

Migration introduces new alleles into a population and can change allele frequencies. Gene flow is the movement of genes across populations, often through migration.

• Effect: Increases genetic diversity, can merge allele frequencies between populations

• Examples: ABO blood group frequencies, PKU mutation spread, African American ancestry

Genetic Drift

Definition and Effects

Genetic drift is the random change in allele frequencies in a population, especially significant in small populations. It can lead to the fixation or loss of alleles independent of their effect on fitness.

• Bottleneck Effect: A sharp reduction in population size due to a random event, leading to loss of genetic diversity

• Founder Effect: When a new population is established by a small number of individuals, resulting in reduced genetic variation

• Example: Cheetahs share a small number of alleles due to historical bottlenecks

Population	Allele 1	Allele 2	Allele 3	Allele 4
Original	0.4	0.3	0.2	0.1
Bottleneck	0.6	0.2	0.2	0.0

Examples of Founder Effect

• High frequency of Huntington disease in Maracaibo, Venezuela

• High frequency of Variegate Porphyria among Afrikaners in South Africa

• Ellis-van Creveld syndrome among old order Amish in the US and Canada

• High frequency of rare genetic diseases in Finland

Summary Table: Factors Affecting Hardy-Weinberg Equilibrium

Factor	Effect on Population
Stratification	Increases homozygosity in subgroups
Assortative Mating	Can increase or decrease genetic variation
Consanguinity	Increases frequency of autosomal recessive diseases
Mutation & Selection	Alters allele frequencies based on fitness
Gene Flow & Migration	Introduces new alleles, merges populations
Genetic Drift	Random changes, loss of diversity in small populations

Key Equations

• Hardy-Weinberg Equation:

  • $p^2 + 2pq + q^2 = 1$

  • $p + q = 1$

Conclusion

Population genetics provides essential insights into the mechanisms that shape genetic diversity and disease prevalence in human populations. Understanding the factors that affect Hardy-Weinberg equilibrium, such as non-random mating, mutation, selection, gene flow, and genetic drift, is crucial for interpreting patterns of inheritance and evolution.