population expansion

Gao F & Keinan A Explosive genetic evidence for explosive human population growth. Curr Opin Genet Dev 41:130-139.

  • the main limitation of SFS-based methods is that they do not use important information from linkage disequilibrium
  • there is no shortage of complementary methods that are based on LD and haplotype information
  • many of these methods were built on coalescent and hidden Markov models
  • others incorporate inference of identity-by-descent (IBD) and identity-by-state (IBS)
  • non-African populations have experienced at least two severe population bottlenecks5 in their history, one resulting from the Out-of-Africa event and the other likely around the time of the initial split of European and Asian populations
  • different studies reached different estimates for the times and intensities of the population bottlenecks, potentially making the inference of recent history sensitive to the specific values assumed for these ancient events
  • Table 1 presents estimates of the more intense Out-of-Africa bottleneck from these studies that have been later used as the basis for inferring recent changes in population size
  • based on exome sequencing data of 1351 Europeans, as part of the Exome Sequencing Project (ESP), Tennessen et al. [10˙˙] assumed the ancient history of [36], and estimate two separate recent epochs of exponential growth to accommodate the possibility of accelerated growth, which is supported by the census data [13]
  • their estimates point to a mild growth during the first epoch — which is assumed to start at a fixed time of 23 kya, corresponding to a European-Asian split according to [36] — at a rate of 0.307% (0.301–0.313%)
  • this mild growth epoch, starting with ~1000 individuals and ending with ~9000 individuals, essentially corresponds to the recovery from the second bottleneck in models assumed by other studies, whether that growth is instantaneous or exponential
  • exact parameter estimates are different between the different studies, which is partially due to the assumed model of ancient history
  • they all clearly point to explosive growth in European population size that culminates in an extant effective population size on the order of magnitude of a million individuals
  • all of the above studies estimated an assumed a single recent epoch of exponential growth, with one study [10˙˙] attempting to describe acceleration in the rate of recent growth by modeling two such epochs
  • two recent studies considered the theoretical impact of growth that is super-exponential (accelerating) or sub-exponential (decelerating) on the SFS
  • with much larger sample size that allows observing variants of much lower frequency, this model of European history has been expanded to predict more extreme growth and much larger extant population size
  • the reason for MSMC's results being inaccurate during recent time is the availability of few haplotypes at that time, with the point estimate for the extant population size being especially unreliable due to the nature of the methodology
  • (personal communication with Stephan Schiffels and Richard Durbin)
  • another recent non-parametric method, stairway plot by Lin and Fu [20˙˙] has been tested on the whole-genome sequencing of each of 9 populations from 1000 Genomes Project phase 1 data
  • recent explosive growth was not observed
  • the results during the last 10,000 years are inaccurate
  • (as per personal communication with Xiaoming Liu)
  • the inference power of very recent history is highly influenced by singletons, for which calling is less reliable in the analyzed low-coverage sequencing data
  • a recent study [64] [...] concluded that due to explosive growth, the population as a whole carries orders of magnitude more deleterious rare mutations but that each individual is expected to carry only a slightly larger fraction of deleterious variants than in the absence of growth
  • it further showed the efficiency of selection due to the larger population size in reducing the frequency of the very deleterious variants, resulting in each individual carrying variants that are a little less harmful than otherwise expected
  • a more recent study [...] [65] reported that following explosive growth each individual carries a smaller number of deleterious mutations overall
  • very weakly deleterious mutations are considered as neutral rather than deleterious