polygenic adaptation - senecio7の日記

Olson-Manning CF, Wagner MR & Mitchell-Olds T 2012 Adaptive evolution: evaluating empirical support for theoretical predictions. Nat Rev Genet 13:867-877.

in humans and other species with expanding populations, very large samples (consisting of >10,000 individuals) are needed to identify the rare, young polymorphisms that reflect current N_e values and that may contribute to disease or adaptation from new mutations
consistent with our small historical N_e of ~10,000 (REF. 10), there are few clear examples of new alleles that have spread rapidly to fixation in human populations
recent population expansion has increased human N_e (to ~1.1 million in Europe)⁹, resulting in many rare variants that contribute to complex trait variation and disease

Drosophila melanogaster has a large N_e and appears to gain adaptive alleles frequently from new mutations

as expected, the species with the highest historical N_e had the most adaptive evolution and the most purifying selection
in two species of Drosophila, higher N_e values did not correlate with estimated adaptive evolution¹⁸, emphasizing that other factors also have an impact on adaptive evolutionary change

where do adaptive alleles come from?
if adaptation primarily depends on new mutations, then adaptive change may be limited by the time needed for new mutations to arise and by their stochastic loss
alternatively, a pre-existing neutral allele can drift to intermediate frequency and can later become advantageous when selection pressures change owing to environmental change or to colonization of a new habitat
such pre-existing alleles may have already recombined onto several genetic backgrounds, which also 'hitchhike' to a higher frequency with the favoured allele¹⁹ in a process known as a soft sweep

Box 1 | Inferences about adaptive evolution from sequence data: caveats
identifying soft selective sweeps has been one of the most challenging problems in molecular population genetics
soft sweeps are more likely when populations are large or when mutation rates are high
small populations or low mutation rates favour hard sweeps from a single, new mutation
soft sweeps are more likely in widely distributed species with low migration rates²⁷, facilitating parallel sweeps in different parts of a species range

modest changes in allele frequencies at many loci can increase population fitness
the raw material for polygenic adaptation may come from standing variation
slight changes in gene frequencies support the fine-tuning of a trait to a new or changing environment
does theory predict whether adaptive alleles are more likely to arise from new mutations, fixation of standing variation or modest changes at many loci?
the answer lies in the effect size of the mutation on fitness

the fixation of alleles is clearly important to adaptation
it is not required for large changes in phenotype¹¹, which may result from slight changes in allele frequency at many loci
such changes are usually difficult to detect, yet several directed evolution studies in D. melanogaster^{34, 35} support this model of adaptation by polygenic allele frequency changes
human populations that span a wide range of geographic locations and climates also appear to have evolved in this manner

few examples of hard sweeps have been found in genome-wide studies of species with a small historical N_e
some combination of soft sweeps and polygenic allele frequency changes may influence adaptive variation of complex traits

introgression between domesticated species and their wild relatives is an intriguing source of new alleles

at least 180 loci control variation within and among populations and together explain ~10% of phenotypic variation in height
some small-effect genes controlling human height also have pleiotropic influences on other traits, especially physiological components related to type 2 diabetes risk

phenotypically extreme individuals may reflect non-additive gene action or rare, large-effect alleles
genes that contribute to both Mendelian and complex diseases in humans⁵¹ show different molecular and network properties compared to loci controlling only Mendelian or only complex diseases
genes that control both complex and Mendelian diseases are longer, more highly transcribed, more tissue-specific in their expression and are embedded in more complex protein networks
the position of a gene product in its biochemical or regulatory network influences its effect size

other loci may tolerate more mutational changes and may accumulate genetic variants that could become adaptive after a change in environment or genetic background

contrary to theoretical predictions, downstream genes in the insulin and TOR pathways are more constrained than upstream genes in Caenorhabditis spp.⁶³, vertebrates⁶⁴ and Drosophila spp.⁶⁵
the pleiotropic effects of downstream genes simply have greater fitness consequences than those of upstream genes
differential expression level is the best explanation for stronger purifying selection on downstream insulin and TOR genes

adaptive alleles are more likely to arise in areas of high recombination
in humans, divergence among populations is negatively correlated with recombination rate⁹⁵, suggesting that alleles in areas of high recombination can spread more easily among populations because they are less constrained by linked deleterious mutations

conflicting results prevent resolution of long-standing theoretical debates about the roles of hard and soft selective sweeps