population expansion - senecio7の日記

Keinan A & Clark AG 2012 Recent explosive human population growth has resulted in an excess of rare genetic variants. Science 336:740-743.

for European history, these studies estimated as much as 0.5% growth in effective population size per generation since the split of the ancestors of Europeans and East Asians ~1000 generations ago, resulting in an effective population size of a few tens of thousands today
these studies did not capture the full scope of human expansion, which may be due to the models not allowing for a recent acceleration in growth rate (5)
the limited sample size of these studies (at most 60 individuals), which only allowed capturing variants of frequency as low as ~1% in the sample, has provided a limited view of rare variants in the population
rare variation adds information on mutations that have occurred during recent epochs of accelerated explosive growth and that may be identified from sequencing larger sample sizes
several ongoing projects are sequencing ever-larger numbers of individuals genome-wide
learning from the frequencies of genetic variants about the demographic history during the past 10,000 years requires capturing variants that entered the population in that time span
many such variants are likely to be rare in the population as a whole (i.e., frequency <0.1%; see below), requiring sequencing of a larger sample of individuals than previously considered in demographic studies

it is also necessary to address how assumptions underlying most population genetic analysis tools are violated with samples of thousands or more individuals
this may require generalizations of population genetics theory to cases in which the sample size is not necessarily smaller than the historical effective population size
considering a sample of 10,000 individuals, the number of singletons estimated was at least 5 times that predicted by the standard Wright-Fisher model (18)
the expected number of doubletons was at least 3 times the prediction

the model estimates pointed to a recent extreme growth of 9.4% per generation [95% Bayesian credible interval (CI), 4.5 to 14.5%], starting 1400 years ago (95% CI, 900 to 2800 years ago)
the current global human population growth rate is estimated at 1.1% per year, equivalent to about 30% per generation
the present effective population size of Europeans as estimated by the model is 1.1 million (95% CI, 0.3 to 1.9 million) (18)

a larger sample size allows identification of rarer polymorphisms that are, on average, due to more recent mutations
the larger the sample size, the more recent the epoch it probes
the excess of rare variants found with a large sample size predicts a growth of 5 to 14% per generation over the past 900 to 2800 years, compared to models of smaller sample size that predicted growth of between 0.2 and 0.7% over a longer period of 20,000 to 30,000 years (5, 6)

we contrasted three simplified models of population history to exemplify the general effects of recent explosive growth and sample size on the SFS
the expected SFS under the three models (Fig. 2) points to considerable inflation in the fraction of variants that are singletons when recent growth is introduced in model 3
Fig. 2
(i) a population that has been of constant size throughout history
(ii) a model previously fit to the derived allele frequency spectrum of Europeans, which includes an out-of-Africa population bottleneck and a second, more recent, population bottleneck (21)
(iii) the same two-bottleneck model of European history with the addition of recent exponential growth from a population size of 10,000 at the advent of agriculture to an extant effective population size of 10,000,000, which amounts to 1.7% growth per generation during the last 400 generations

explosive growth also results in a haplotype structure that deviates from the prediction of standard population genetics
recombination will not have broken down linkage disequilibrium between rare mutations and neighboring common variants