polygenic adaptation

Fu W & Akey JM 2013 Selection and adaptation in the human genome. Annu Rev Genom Hum Genet 14:467-489.

  • the probability of a sweep from standing variation increases with larger effective population sizes
  • this observation has important implications for recent human evolutionary history, which has seen an explosion in population size
  • selection occurring over the past 5,000–10,000 years did so primarily by acting on standing variation
  • selection from standing variation is expected to be common in recent human history
  • many of the substrates of positive selection in the human genome await discovery
  • they do not leave signatures in patterns of genetic variation that most neutrality test statistics are designed to detect
  • a typical trait has a large repository of standing variants for selection to act on
  • selection acting simultaneously on many preexisting variants would be an efficient mechanism for phenotypic adaptation
  • if the optimal phenotypic value changes, perhaps because of a change in the environment, then the population will adapt by allele frequency shifts at many loci
  • polygenic selection pulls alleles up and down in frequency but generally not to fixation
  • the frequencies of alleles associated with increased height are systematically elevated in northern Europeans compared with southern Europeans (p < 4.3 × 10−4), which is consistent with widespread weak selection with selection coefficients on the order of ~10−3–10−5 per allele per generation compared with genetic drift alone
  • several genome-wide approaches have been developed to detect signatures expected from polygenic selection
  • Tennessen & Akey (143) found significant evidence for parallel adaptive divergence in geographically diverse populations, consistent with modest shifts in allele frequencies at many loci
  • another promising approach for detecting polygenic selection is to compare allele frequencies with environmental variables while controlling for population structure
  • collectively, these studies suggest that polygenic selection may be widespread in humans
  • more theoretical and empirical work needs to be done to better understand models involving subtle shifts of allele frequencies at many loci and how best to detect this mechanism of adaptation
  • the classic selective sweep model and outlier-based genome-wide scans for selection have served the field well
  • this mode of selection has not played a prominent role in recent human evolutionary history
  • most of the dramatic signatures of a hard sweep have been identified
  • theoretical studies that explore the dynamics of more realistic mechanisms of evolutionary change, such as polygenic and epistatic selection, will be important for developing novel statistical methods to detect signatures from different modes of adaptive evolution