Population genetics
Population genetics is a subfield of genetics that deals with genetic differences within and among populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and population structure.[1]
Population genetics was a vital ingredient in the emergence of the modern evolutionary synthesis. Its primary founders were Sewall Wright, J. B. S. Haldane and Ronald Fisher, who also laid the foundations for the related discipline of quantitative genetics. Traditionally a highly mathematical discipline, modern population genetics encompasses theoretical, laboratory, and field work. Population genetic models are used both for statistical inference from DNA sequence data and for proof/disproof of concept.[2]
What sets population genetics apart from newer, more phenotypic approaches to modelling evolution, such as evolutionary game theory and adaptive dynamics, is its emphasis on such genetic phenomena as dominance, epistasis, the degree to which genetic recombination breaks linkage disequilibrium, and the random phenomena of mutation and genetic drift. This makes it appropriate for comparison to population genomics data.
Four processes[edit]
Selection[edit]
Natural selection, which includes sexual selection, is the fact that some traits make it more likely for an organism to survive and reproduce. Population genetics describes natural selection by defining fitness as a propensity or probability of survival and reproduction in a particular environment. The fitness is normally given by the symbol w=1-s where s is the selection coefficient. Natural selection acts on phenotypes, so population genetic models assume relatively simple relationships to predict the phenotype and hence fitness from the allele at one or a small number of loci. In this way, natural selection converts differences in the fitness of individuals with different phenotypes into changes in allele frequency in a population over successive generations.
Before the advent of population genetics, many biologists doubted that small differences in fitness were sufficient to make a large difference to evolution.[9] Population geneticists addressed this concern in part by comparing selection to genetic drift. Selection can overcome genetic drift when s is greater than 1 divided by the effective population size. When this criterion is met, the probability that a new advantageous mutant becomes fixed is approximately equal to 2s.[16][17] The time until fixation of such an allele is approximately .[18]
Linkage[edit]
If all genes are in linkage equilibrium, the effect of an allele at one locus can be averaged across the gene pool at other loci. In reality, one allele is frequently found in linkage disequilibrium with genes at other loci, especially with genes located nearby on the same chromosome. Recombination breaks up this linkage disequilibrium too slowly to avoid genetic hitchhiking, where an allele at one locus rises to high frequency because it is linked to an allele under selection at a nearby locus. Linkage also slows down the rate of adaptation, even in sexual populations.[62][63][64] The effect of linkage disequilibrium in slowing down the rate of adaptive evolution arises from a combination of the Hill–Robertson effect (delays in bringing beneficial mutations together) and background selection (delays in separating beneficial mutations from deleterious hitchhikers).
Linkage is a problem for population genetic models that treat one gene locus at a time. It can, however, be exploited as a method for detecting the action of natural selection via selective sweeps.
In the extreme case of an asexual population, linkage is complete, and population genetic equations can be derived and solved in terms of a travelling wave of genotype frequencies along a simple fitness landscape.[65] Most microbes, such as bacteria, are asexual. The population genetics of their adaptation have two contrasting regimes. When the product of the beneficial mutation rate and population size is small, asexual populations follow a "successional regime" of origin-fixation dynamics, with adaptation rate strongly dependent on this product. When the product is much larger, asexual populations follow a "concurrent mutations" regime with adaptation rate less dependent on the product, characterized by clonal interference and the appearance of a new beneficial mutation before the last one has fixed.
Applications[edit]
Explaining levels of genetic variation[edit]
Neutral theory predicts that the level of nucleotide diversity in a population will be proportional to the product of the population size and the neutral mutation rate. The fact that levels of genetic diversity vary much less than population sizes do is known as the "paradox of variation".[66] While high levels of genetic diversity were one of the original arguments in favor of neutral theory, the paradox of variation has been one of the strongest arguments against neutral theory.
It is clear that levels of genetic diversity vary greatly within a species as a function of local recombination rate, due to both genetic hitchhiking and background selection. Most current solutions to the paradox of variation invoke some level of selection at linked sites.[67] For example, one analysis suggests that larger populations have more selective sweeps, which remove more neutral genetic diversity.[68] A negative correlation between mutation rate and population size may also contribute.[69]
Life history affects genetic diversity more than population history does, e.g. r-strategists have more genetic diversity.[67]
Detecting selection[edit]
Population genetics models are used to infer which genes are undergoing selection. One common approach is to look for regions of high linkage disequilibrium and low genetic variance along the chromosome, to detect recent selective sweeps.
A second common approach is the McDonald–Kreitman test which compares the amount of variation within a species (polymorphism) to the divergence between species (substitutions) at two types of sites; one assumed to be neutral. Typically, synonymous sites are assumed to be neutral.[70] Genes undergoing positive selection have an excess of divergent sites relative to polymorphic sites. The test can also be used to obtain a genome-wide estimate of the proportion of substitutions that are fixed by positive selection, α.[71][72] According to the neutral theory of molecular evolution, this number should be near zero. High numbers have therefore been interpreted as a genome-wide falsification of neutral theory.[73]
Demographic inference[edit]
The simplest test for population structure in a sexually reproducing, diploid species, is to see whether genotype frequencies follow Hardy-Weinberg proportions as a function of allele frequencies. For example, in the simplest case of a single locus with two alleles denoted A and a at frequencies p and q, random mating predicts freq(AA) = p2 for the AA homozygotes, freq(aa) = q2 for the aa homozygotes, and freq(Aa) = 2pq for the heterozygotes. In the absence of population structure, Hardy-Weinberg proportions are reached within 1–2 generations of random mating. More typically, there is an excess of homozygotes, indicative of population structure. The extent of this excess can be quantified as the inbreeding coefficient, F.
Individuals can be clustered into K subpopulations.[74][75] The degree of population structure can then be calculated using FST, which is a measure of the proportion of genetic variance that can be explained by population structure. Genetic population structure can then be related to geographic structure, and genetic admixture can be detected.
Coalescent theory relates genetic diversity in a sample to demographic history of the population from which it was taken. It normally assumes neutrality, and so sequences from more neutrally evolving portions of genomes are therefore selected for such analyses. It can be used to infer the relationships between species (phylogenetics), as well as the population structure, demographic history (e.g. population bottlenecks, population growth), biological dispersal, source–sink dynamics[76] and introgression within a species.
Another approach to demographic inference relies on the allele frequency spectrum.[77]
Evolution of genetic systems[edit]
By assuming that there are loci that control the genetic system itself, population genetic models are created to describe the evolution of dominance and other forms of robustness, the evolution of sexual reproduction and recombination rates, the evolution of mutation rates, the evolution of evolutionary capacitors, the evolution of costly signalling traits, the evolution of ageing, and the evolution of co-operation. For example, most mutations are deleterious, so the optimal mutation rate for a species may be a trade-off between the damage from a high deleterious mutation rate and the metabolic costs of maintaining systems to reduce the mutation rate, such as DNA repair enzymes.[78]
One important aspect of such models is that selection is only strong enough to purge deleterious mutations and hence overpower mutational bias towards degradation if the selection coefficient s is greater than the inverse of the effective population size. This is known as the drift barrier and is related to the nearly neutral theory of molecular evolution. Drift barrier theory predicts that species with large effective population sizes will have highly streamlined, efficient genetic systems, while those with small population sizes will have bloated and complex genomes containing for example introns and transposable elements.[79] However, somewhat paradoxically, species with large population sizes might be so tolerant to the consequences of certain types of errors that they evolve higher error rates, e.g. in transcription and translation, than small populations.[80]