Population Genetics Signatures of Selection

Types of Selection

  • Positive Selection: Increases the frequency of beneficial alleles.
  • Negative Selection: Decreases the frequency of deleterious alleles.
  • Balancing Selection: Maintains multiple alleles in a population.
  • Frequency Dependent Selection: Fitness of a genotype depends on its frequency.
  • Background Selection: Selection against linked deleterious mutations.
  • Runaway Selection: Selection for a trait drives selection for another related trait.
  • Heterosis (Hybrid Vigor): Increased fitness of heterozygous individuals.

Selection Dynamics

  • Negative Selection: Phenotype and genotype frequencies change after selection, targeting a specific genetic locus.
  • Positive Selection: Similar to negative selection, phenotype and genotype frequencies shift, affecting a genetic locus.
  • Balancing Selection: Phenotype and genotype frequencies change, maintaining diversity at a genetic locus.

Demographic Effects on Selection Signatures

  • Demography, including stable population and population expansion, can confound the detection of selection signatures.

Haplotypes vs. Single SNPs

  • SNPs (Single Nucleotide Polymorphisms): Individual variations in DNA sequence.
  • Haplotypes: Combinations of SNPs on the same chromosome, providing more comprehensive genetic information.
  • Haplotypes carry information on stretches of correlated points

Fst

  • F_{st} is a measure of population differentiation based on allele frequencies.
  • F{st} = \frac{HT - HS}{HT}
    • Where H_T is the expected heterozygosity in the total population.
    • H_S is the average heterozygosity within subpopulations.
  • Differences in SNPs and Haplotypes between populations can be quantified using F_{st}.

Tajima's D

  • Tajima’s D is a test statistic used to detect selection by comparing two estimates of nucleotide diversity:
    • \pi (Pi): average number of pairwise differences.
    • \Theta (Theta): based on the number of segregating sites (Watterson's estimator).
  • Formulas:
    • \Theta_{\pi} = \pi = {\frac{1}{n} \Sigma \frac{differences}{(n*length)}}
    • \Theta_S = S = {\frac{S}{\Sigma \frac{1}{i}}}
  • Interpretation:
    • \Theta{\pi} \approx \ThetaS ; D \approx 0: Indicates neutrality/equilibrium.
    • \Theta{\pi} < \ThetaS ; D < 0: Suggests positive selection.
    • \Theta{\pi} > \ThetaS ; D > 0: Suggests balancing selection.
  • Theta and the coalescent: \Theta = 4N_e\mu

Quantitative Trait Loci (QTL)

  • Quantitative genetics deals with phenotypes and statistics.
  • The phenotype is determined by both genes and environment.
  • P = G + E (Phenotype = Genotype + Environment).
  • Var(P) = Var(G) + Var(E)
  • Broad sense heritability: H^2 = \frac{Var(G)}{Var(P)}
  • Additive genetic variance (Var(A)) is the part of genetic variance that results in a response to selection.
  • Narrow sense heritability: h^2 = \frac{Var(A)}{Var(P)}

Estimating Heritability

  • Crosses are performed within two populations of individuals selected from the extremes of the phenotypic distribution in the parental generation.
  • If the phenotypic distributions of the two groups of offspring are significantly different from each other, then the trait is heritable.
  • If both offspring distributions resemble the distribution for the parental generation, then the trait is not heritable.

Truncation Selection Experiment

  • Only individuals larger than a certain threshold are allowed to reproduce.
  • The individuals represented by the shaded proportion of the frequency curve reproduce, the other do not. The mean of the whole population is \mu. The mean of those reproducing is \mu_s.
  • The selection differential S = \mu_s - \mu. As a result of selection, the frequency distribution moves to the right. The mean of the next generation is \mu' and the selection response R = \mu' - \mu.
  • The heritability can be estimated from the response to selection as h^2 = \frac{R}{S}.

Mapping QTL

  • Recombinant Inbred Lines(RILs)
    • Inbred parents that differ in the density of trichomes are crossed to form an F1 population with intermediate trichome density.
    • An F1 individual is selfed to form a population of F2 individuals.
    • Each F2 is selfed for six additional generations, ultimately forming several recombinant inbred lines (RILs).
    • Each RIL is homozygous for a section of a parental chromosome. The RILs are scored for several genetic markers, as well as for the trichome density phenotype

Mapping Designs

  • F2
  • Backcrossing
  • Recombinant inbred lines

Mapping statistics

  • Single locus tests: regression, t-test, ANOVA
  • Interval mapping
  • Multiple QTLs: e.g. composite interval mapping, multiple QTL mapping, genetic algorithms

Examples of QTL

  • Growth in snapper (Chrysophrys auratus)
  • QTLs of dorsal fin in goldfish (Carassius auratus)

Summary

  • Demography can confound selection signatures.
  • Positive selection looks like a population expansion.
  • Haplotypes can convey more statistical power to detect selection.
  • Frequency Dependent Selection looks like a combination of positive and negative selection.
  • Narrow-sense heritability can be measured with molecular markers and experiments.
  • Recombinant Inbred Lines (RILs) can quickly facilitate mapping QTLs.
  • Correlative methods between phenotypes and genotypes are powerful to detect markers under selection.