Population Structure, Selection, and Drift

Vocabulary flashcards covering population structure, genetic drift, effective population size, natural selection types, and genetic disease persistence from the Block II Medical Genetics lecture.

Evolution

A change in allele frequencies in a population over time.

Genetic Drift

A process of random sampling in finite populations where certain alleles become over-represented or under-represented each generation by chance, consistently leading to a loss of genetic variation.

Effective Population Size ($N_e$)

The size of an idealized population undergoing random mating and constant census size that experiences genetic drift at the same rate as the actual population; factors such as founder effects, bottlenecks, sex-ratio imbalances, and popular sires reduce $N_e$ below the census size ($N$).

Extinction Risk Thresholds for $N_e$

Rule-of-thumb thresholds in conservation genetics indicating that populations with $N_e$ below approximately $500$ are at risk of extinction over the long term, and those below approximately $50$ face an urgent risk.

Wahlund Effect

A deficit of heterozygotes that occurs when distinct subpopulations with different allele frequencies are analyzed together as a single total population, even if each subpopulation is in Hardy-Weinberg equilibrium.

$$F_{st}$$

A metric that quantifies genetic differentiation between groups (populations, subpopulations, or species) by measuring the reduction in heterozygosity due to allele frequency differences between subpopulations ($s$) compared to the total population ($t$).

Selection Coefficient ($s$)

A quantitative measure of the strength of selection acting on a genetic variant (for example, $s = -0.1$ corresponds to a $10\%$ reduction in fitness or surviving offspring to adulthood).

Nearly Neutral Variant

A mutation with a selection coefficient so close to zero that it falls within the range $-1/N_e < s < 1/N_e$, causing its frequency trajectory in the population to be governed primarily by drift rather than selection.

Additive Mutation

A mutation where heterozygotes possess an intermediate fitness between the two homozygotes; it becomes fixed the quickest because heterozygotes are favored initially over wildtypes, and homozygous mutants are subsequently favored over heterozygotes.

Stabilizing Selection

A mode of natural selection that favors intermediate phenotypes and acts against phenotypic extremes, moving or maintaining a trait toward the population mean.

Directional Selection

A mode of natural selection that favors individuals at one extreme of the phenotypic distribution, causing the population mean for that trait to shift in that direction over time.

Diversifying (Disruptive) Selection

A mode of natural selection that favors individuals at both phenotypic extremes over intermediate individuals, which at its extreme can result in reproductive isolation and speciation.

Genetic Hitchhiking

The process whereby linked neutral or deleterious alleles on the same haplotype increase in frequency along with a positively selected mutation.

Selective Sweep

The rapid fixation of a positively selected allele along with all linked genetic variants on that same haplotype, dramatically reducing local genetic variation.

Epistasis

Genetic interactions between different variants where the phenotypic effect of a specific mutation depends on the genetic background in which it is found.

Gene $\times$ Environment ($G \times E$) Interaction

The occurrence where different genotypes result in distinct phenotypic outcomes depending on environmental conditions (e.g., the CETP TaqIB allele protecting from heart disease in moderate drinkers, but not in non-drinkers).

Pleiotropy

The phenomenon where a single genetic variant produces multiple distinct phenotypic effects (e.g., genetic variants conferring white coat patterns that also increase the risk of deafness in dogs and cats).

Balancing Selection

A category of selection that maintains multiple alleles in a population over time, often driven by environmental heterogeneity or heterozygote advantage.

Heterozygote Advantage (Overdominance)

A form of balancing selection wherein heterozygous individuals have higher fitness than either homozygous genotype (e.g., protection from malaria in humans with the sickle cell allele, or faster sprinting in whippets with one copy of the MSTN mutation).

Dominance Coefficient ($h$)

A parameter defining the relative strength of selection acting on heterozygous individuals, equaling $0$ for recessive traits, $0.5$ for additive traits, $1$ for dominant traits, and $h > 1$ (if $s > 0$) or $h < 0$ (if $s < 0$) for overdominant traits.

Inbreeding Depression

The reduction in population fitness caused by inbreeding, which elevates homozygosity across the genome and consequently increases the expression of recessive and partially recessive deleterious disease alleles ($h < 0.5$).