Formulating a historical and demographic model of recent human evolution based on resequencing data from noncoding regions

Abstract

Background: Estimating the historical and demographic parameters that characterize modern human populations is a fundamental part of reconstructing the recent history of our species. In addition, the development of a model of human evolution that can best explain neutral genetic diversity is required to identify confidently regions of the human genome that have been targeted by natural selection.

Methodology/principal findings: We have resequenced 20 independent noncoding autosomal regions dispersed throughout the genome in 213 individuals from different continental populations, corresponding to a total of approximately 6 Mb of diploid resequencing data. We used these data to explore and co-estimate an extensive range of historical and demographic parameters with a statistical framework that combines the evaluation of multiple models of human evolution via a best-fit approach, followed by an Approximate Bayesian Computation (ABC) analysis. From a methodological standpoint, evaluating the accuracy of the parameter co-estimation allowed us to identify the most accurate set of statistics to be used for the estimation of each of the different historical and demographic parameters characterizing recent human evolution.

Conclusions/significance: Our results support a model in which modern humans left Africa through a single major dispersal event occurring approximately 60,000 years ago, corresponding to a drastic reduction of approximately 5 times the effective population size of the ancestral African population of approximately 13,800 individuals. Subsequently, the ancestors of modern Europeans and East Asians diverged much later, approximately 22,500 years ago, from the population of ancestral migrants. This late diversification of Eurasians after the African exodus points to the occurrence of a long maturation phase in which the ancestral Eurasian population was not yet diversified.

Figure 1. Minor allele and derived allele frequency spectra.

(A) Minor allele frequency (MAF) and (B) derived allele frequency (DAF) spectra computed by merging the 20 non coding autosomal DNA sequences. The expected MAF and DAF spectra (grey bars) were obtained assuming constant population sizes (Material and Methods). To focus on low frequency bins, the MAF spectrum display values lower than 35 counts in each continental population. To show the derived alleles that are fixed in each continental population, we arbitrarily removed intermediate bins in the DAF spectrum.

Figure 2. Sequenced-based summary statistics in Africans, Europeans and East-Asians.

Biplots of Tajima's D and Fu and Li's F* computed for each genomic region separately, in Africans (A), Europeans (B) and East-Asians (C). Significant Tajima's D values (P<0.05) are indicated in blue, in green for Fu and Li's F* only, and in red for both. Biplots of the number of haplotypes (K) and polymorphisms (S) computed for each genomic region separately in Africans (D), Europeans (E) and East-Asians (F). Significant K values (P<0.05) are indicated in blue, in green for S, and in red for both. The grey dots indicate the expected values of each genomic region simulated assuming a constant population size model (simulation procedure and significance of each region are described in the Materials and Methods section).

Figure 3. Model and parameter best-fitted estimations.

(A) Simulations considering different levels of replacement of archaic hominids by modern humans. We performed 8 sets of 10⁵ simulations: one set for a replacement rate δ = 0, one for δ = 1, 3 sets for 0≤δ≤0.01, 0≤δ≤0.1 and 0≤δ≤0.5, and 3 sets for δ≥0.5, δ≥0.9 and δ≥0.99. For each of the 8 sets, we considered three models of ancestral migration (represented by black arrows): a residual ancestral migration rate (m₀∼10⁻¹⁰), an ancestral migration rate with the same range (10⁻⁶ to 4×10⁻³) as m the current migration rate (represented by gray arrows), and an ancestral migration twice higher than m. Among the 24 models tested, the model assuming a complete replacement rate of archaic hominids (δ = 1) and a residual ancestral migration (m₀∼10⁻¹⁰) exhibited the significantly highest ψ₁ except when compared with the model assuming an almost complete replacement rate of archaic hominids (δ≥0.99). This best-fitted range of parameters (δ≥0.99 and m₀∼10⁻¹⁰), indicated by the yellow/orange/white area (A), was therefore used to simulate the African expansion (B) and the non African bottleneck (C). We performed three sets of 10⁵ simulations for the onset t_A: 0≤t_A≤25 Kyears, 25≤t_A≤50 Kyears and 50≤t_A≤75 Kyears. For each of the three sets, we considered 5 models of growth rate α_A parameters; α_A = 0, 0≤α_A≤0.005, 0.005≤α_A≤0.01, 0.01≤α_A≤0.015 and 0.015≤α_A≤0.02. Among the 15 models tested, the best-fitted ranges of parameters (ψ₁ significantly higher than ψ₁ of the constant size model α_A = 0, P<0.01) are indicated by the yellow/orange/white area (B). Likewise, we performed 5 sets of 10⁵ simulations assuming bottlenecks intensities β_OoA, starting at the time of the out-of-Africa exodus (T_OoA) and ending at the independent Neolithic expansions in Europe and east-Asia: β_OoA = 1, 1≤β_OoA≤2, 2≤β_OoA≤20, 20≤β_OoA≤40 and 40≤β_OoA≤60. The best-fitted range of parameter (ψ₁ significant higher than ψ₁ of the constant size model β_OoA = 1, P<0.01), indicated by the yellow/orange/white area (C), was obtained with the set of priors 2≤β_OoA≤20. The distributions used are specified in Table S4.

Figure 4. Models of recent African origin involving different dispersal scenarios.

(A) General RAOEB model best fitting the data, with parameter ranges given in Table 2. This model assumes a single out-of-Africa dispersal followed by the European and East-Asian split. (B) RAOEB model involving two independent, concomitant dispersals out of Africa, each giving rise to Europeans and East-Asians. (C) RAOEB model involving two independent dispersals out of Africa occurring at different times, the earlier giving rise to Europeans. (D) RAOEB model involving two independent dispersals out of Africa occurring at different times, the earlier giving rise to East Asians. For models B–D, the ranges of parameters are the same as those given in Table 2. The alternative dispersal model B (two independent dispersals at the same time) was performed using a split of the two non Africans populations concomitant with the time of out-of-Africa exodus (T_OoA) simulated with the same prior reported in Table 2. The two alternative dispersal models C and D (two independent dispersals at different times) were simulated using times for the first out-of-Africa exodus drawn from the first half of the prior distribution of T_OoA (Table 2), while times for the second out-of-Africa exodus were drawn from the second half of the prior distribution of T_OoA. (E) Posterior probability estimated for the 4 possible dispersal models represented in A, B, C, and D.

Figure 5. Approximate posterior distributions of historical and demographic parameters.

This figure gives the estimated ABC posterior distributions of the historical and demographic parameters (Table 3) using the RAOEB model (Figure 4A) with best-fitted priors (Table 2). Black lines represent the prior distributions and grey bars the posterior distributions. The times were translated into years using a generation time equal to 25 years. The posterior distributions of the parameters where the estimations were not validated by means of the accuracy evaluation procedure are not presented (i.e. N_A and δ).