Out of Africa and Back Again? Jan 13, 2019 20:09:52 GMT
Post by Admin on Jan 13, 2019 20:09:52 GMT
The routes followed by fully modern humans as they expanded out of Africa 50,000–100,000 years ago into Eurasia have long been a central question of anthropology1 and have important implications for understanding the evolutionary history of all non-African populations. So far, neither fossil and archaeological2–4 nor genetic5,6 evidence has been able to distinguish between an exit through Egypt and Sinai (northern route)7 or one through Ethiopia, the Bab el Mandeb strait, and the Arabian Peninsula (southern route).8–10 Genetic evidence has more often been interpreted as favoring a southern route,5,6,9 although the Neandertal admixture present in all non-Africans11 is more readily explained by a northern route given that Neandertal fossils are currently known from the Levant, but not from the southern part of the Arabian Peninsula.12 Thus, the available evidence remains inconclusive. Information to discriminate between the northern and southern routes might still be present in Africa within the full genomes of the populations inhabiting modern Egypt and the Horn of Africa, and thus further investigation is warranted. However, although it might not be easy to extract this information because of the past and recent genetic introgression experienced by these populations,13,14 full sequences of Northeast African genomes would provide the best starting point for these and other analyses.
Using ADMIXTURE17 and principal-component analysis (PCA)18 (Figure 1A), we estimated the average proportion of non-African ancestry in the Egyptians to be 80% and dated the midpoint of the admixture event by using ALDER20 to around 750 years ago (Table S2), consistent with the Islamic expansion and dates reported previously.13,14 The Ethiopian populations showed, as expected, a more variable spectrum of genetic introgression (Figure 1B). Consistent with previous reports,13 the Amhara and Oromo were shown to have around 50% of their genome derived from non-Africans, the introgressed proportion in the Somali and Wolayta amounted to 40%–30%, and the Gumuz showed negligible amounts of non-African admixture. The date of the midpoint of these admixture events was 2,500–3,000 years ago (Table S2), although one notable exception was the Oromo, who have shown evidence of multiple admixture events.21 These conclusions are consistent with previous reports13,21 and fit with linguistic records.22 Furthermore, the distribution of maternal (mtDNA) and paternal (Ychr) lineages revealed sex-biased admixture patterns in Ethiopians (Figure S2), such that there was less male-mediated than female-mediated Middle Eastern backflow. The affinity of the Egyptian African component with the modern East and West African populations (green component in Figure 1B, K = 5) could be due to either a continuity of human presence in the area or recent gene flow from neighboring African regions resulting from demographic processes and slave trade over the last two millennia.23
PCA and ADMIXTURE Analysis
In order to filter out, through masking, the Eurasian portion identified in this way, we phased the samples by using ShapeIT24 and processed them with PCAdmix.25 In the masking process, Europeans (CEU [Utah residents with ancestry from northern and western Europe from the CEPH collection])15 were used as a proxy for the non-African component, and the Gumuz (the Ethiopian population showing minimal introgression) were used as a proxy for the African component. Pairwise FST26 was calculated before and after the masking process (Table S3), highlighting the expected trend of increased distance of the admixed populations from non-Africans when we retained only their African component. After we excluded the Gumuz themselves from the subsequent analyses, we compared the African components of the masked Ethiopian and Egyptian genomes (hereafter referred to as the Ethiopian′ and Egyptian′ genomes, respectively) with a set of West African (YRI [Yoruba in Ibadan, Nigeria]) and OOA populations spanning Eurasia (East Asian CHB [Han Chinese in Beijing, China], European TSI [Toscani in Italia] and CEU [Figure 2], and South Asian GIH [Gujarati Indians in Houston, Texas] [Figure S6]) in order to look for a signature of the OOA migration. Such a signature was defined as a higher similarity between the Ethiopian′ or Egyptian′ genomes and the non-Africans than between the latter and the YRI. If we assume a stepwise differentiation out of Africa, and if the preferential route followed was the northern one, Egyptian′ samples should share the highest number of haplotypes with the Eurasian samples even after recent events of introgression are controlled for. Conversely, Ethiopian′ samples would show the highest haplotype sharing with the Eurasian samples if the southern route was preferentially followed during the OOA migration. We restricted this comparison to 18,114 genomic regions (spanning a total length of 7.1 Mb; Figure S5) containing haplotypes shared by Europeans and Asians because these were likely to predate the split between these populations. Given the broad occurrence of these regions outside Africa, we could rule out positive selection as a plausible driver of the observed linkage-disequilibrium (LD) pattern. We identified these regions by calculating LD blocks in a set of 457 non-African samples. We retrieved 41,141 haplotypes at these loci in the Egyptian′, Ethiopian′, or YRI samples (Figure 2A) and used them to estimate the genetic similarity between OOA populations CHB and TSI and each of the three African populations. 85% of the haplotypes were present in all three African populations and were discarded as non-informative. The remaining 15% of haplotypes were instead observed in only one or two African populations. For these haplotypes that could discriminate between the African populations, the combined CHB and TSI samples showed more Egyptian′-specific (1.25-fold, p = 2 × 10−6) and Ethiopian′- and Egyptian′-specific (hereafter Ethiopian′|Egyptian′-specific) (1.15-fold, p = 9 × 10−6) haplotypes than did any of the other African haplotype sets (Figure 2B). We further explored the observed enrichment of Egyptian′ haplotypes in the CHB and TSI samples by investigating the frequency of each class of haplotype in the combined CHB and TSI samples, and again, the frequencies of Egyptian′-specific and Egyptian′|Ethiopian′-specific haplotypes were highest (Figures 2C and 2D). The enrichment of Egyptian′ haplotypes in the genetic pool of the CHB and TSI samples points to a northern migration as the greater contributor to populations outside Africa.
Haplotype Sharing between African and Non-African Populations
This finding was robust to a wide range of potential artifacts stemming from uncertainties in the masking process (Figures S3, S4, and S6A; Table S4; note particularly the false-positive rate displayed in column 8) and was replicated in a South Asian population (GIH; Figure S6B). Furthermore, we showed with simulations that the error rate present in the masking process (Table S4) was unlikely to affect our findings (Figures S4 and S6). Even when we added a 10% misclassification error to the Ethiopians, Egyptians held as the African population showing the highest affinity to non-Africans. Alternative scenarios involving early back-to-Africa migrations27 as the source of haplotype sharing between Egyptian′ and non-African samples were considered as sources of the observed pattern. However, such confounding backflow would need to have taken place prior to the split between East Asians and Europeans (ca. ∼40,000 years ago) and, if this genetic component originated from the main OOA founding event, is likely to have been removed by the non-African masking procedure, which was designed for this purpose.
To provide an independent test of our finding, we analyzed three Egyptian and five Ethiopian high-coverage genomes with the multiple sequentially Markovian coalescent (MSMC) approach before and after masking and compared them with a set of publicly available high-coverage genomes.15,28 MSMC,29 an extension of the PSMC30 method to two or four genomes, estimates the split time between pairs of genomes. Consistent with their admixed nature, the split times of the non-masked Egyptians and the mixed Ethiopians from Europeans (CEU) and West Africans (YRI) were much closer to each other than to the same split times measured in the non-admixed Ethiopian population (Gumuz) (Figure 3; Figure S7). If we consider the genetic split between two populations as a process gradually occurring over thousands of years, two independent splits might show partial overlaps when their midpoints are less than a few thousand years apart. Keeping in mind this potential confounder, the Ethiopian′ and Egyptian′ genomes showed different patterns. In particular, the Egyptian′ genomes displayed a more recent split from both the West African (21,000 years ago) and the non-African (55,000 years ago) genomes than did the Ethiopian′ genomes (37,000 and 65,000 years ago, respectively). This suggests a higher similarity between non-African and Egyptian′ components than between non-African and Ethiopian′ components, which is consistent with the fact that Egypt is the last stop on the way out of Africa. Such split dates21 also hint at a recent interaction between Egyptians and West Africans (Figure 3).
Inferred Split Times between Pairs of High-Coverage Genomes
In conclusion, the analysis of Ethiopian′ and Egyptian′ whole-genome sequence data identifies modern Egyptians as the African population whose genome and haplotype frequency most closely resemble those of non-African populations. The fact that we could identify in Egyptians an African genomic component that is distinct from West and East African components further supports a minor degree of population continuity in Egypt since the OOA dispersal. These findings point to the northern route as the preferential direction taken out of Africa. In doing this, they resolve the puzzles of archaeological similarities and Neandertal admixture, which are readily accommodated by a northern-exit model, but not by a southern exit, and fit well with the recent discovery of human remains dating to around 55,000 years ago in Israel (close to the northern route).31 Furthermore, the data generated here provide a better source of information for spatially explicit demographic models.32,33 Our analysis does not address controversies about the timing and possible complexities of the expansion out of Africa and highlights the need for further analyses, ideally including ancient DNA, as well as Near Eastern and Papuan or Australian genomes representative of an early coastal expansion, to further resolve these issues.
Am J Hum Genet. 2015 Jun 4; 96(6): 986–991