Migration Route Out of Africa Unresolved by 225 Egyptian and Ethiopian Whole Genome Sequences

摘要

Population structure is a fundamental part of population genetics. In coalescent theory, the impact of population structure or a restriction of gene flow is well-studied (Hudson, 1990 ; Nordborg, 2003 ). Admixture is inter-mating between previously isolated populations, although the biological characteristics of genetically diverged parental populations can be debated. The pairwise sequentially Markovian coalescent model (Li and Durbin, 2011 ) and the multiple sequentially Markovian coalescent model (Schiffels and Durbin, 2014 ), both recently developed methods designed for whole genome sequence analysis, do not model admixture in a formal sense. However, simulations have shown that these models are sensitive to admixture (Li and Durbin, 2011 ), because admixture increases heterozygosity and consequently appears as an increase in the effective population size. The issue of ancient vs. recent admixture, and the actual time depths, is of concern due to the potentially obscuring effects of a range of evolutionary processes. Both of these models divide time into intervals, theoretically permitting detection of events at different time depths. Consequently, these genetic models have the potential to complement anthropological and archeological studies of the distant past. Archeological, fossil, and genetic data collectively remain inconclusive regarding the route(s) of modern humans out of Africa: one possible route was north of the Red Sea through Egypt and Sinai and another possible route was south of the Red Sea across the Bab-el-Mandeb Strait (Beyin, 2011 ). Pagani et al. ( 2015 ) described a population genetic study intended to distinguish between these possibilities. The design of their study involved whole genome sequencing of 100 recent Egyptian emigrants living in Lebanon and 25 Amhara, 25 Oromo, 25 Somali, 25 Wolayta, and 25 Gumuz from present-day Ethiopia. The authors used the 1000 Genomes CEU sample as a proxy for “non-African” ancestry and the Gumuz sample as a proxy for “African” ancestry. They then reconstructed the “African” components of the Egyptian and remaining Ethiopian genomes and compared them to the 1000 Genomes YRI, CHB, TSI, and GIH samples. The authors hypothesized that the “African” component of the Egyptian genomes should be more similar to “non-African” genomes under a northern route. Conversely, the “African” component of the Ethiopian genomes should be more similar to “non-African” genomes under a southern route. The authors reported enrichment of the “African” component of the Egyptian genomes, which they interpreted as evidence in favor of the northern route. The authors' analyses involve two major critical assumptions, one involving population structure and the other involving time. With respect to population structure, the authors assumed that both the Egyptians and Ethiopians could be described using a problematic continental framework, i.e., “African” and “non-African” components which often mask ideas about what constitutes African. Progress has been made: analyses of the genetic structure of autosomal data from global surveys of thousands of individuals have revealed multi-way ancestral compositions at a sub-continental level of resolution, likely reflecting evolution of local or regional populations (Tishkoff et al., 2009 ; Shriner et al., 2014 ). Three limitations of these types of studies are (1) the extent to which convenience samples are used, in comparison to a complete catalog of all ethno-linguistic or biogeographical groups (since ethno-linguistic groups have varying time depths), (2) the extent to which populations in such studies are arbitrary constructs (Gannett, 2003 ), and (3) the appropriateness of divergence by isolation to model the genealogical relationships among ancestries. Given these caveats, the ancestral compositions of samples of modern Egyptians and Ethiopians, as well the reference CEU sample, have been previously estimated (Shriner et al., 2014 ) and are summarized in Table 1 . Notably, the two Egyptian samples we used include a low level of Cushitic ancestry but no Nilo-Saharan ancestry. This absence implies a lack of coverage of the full geographical range of Egyptians, including Nubians who today speak a Nilo-Saharan language (Dobon et al., 2015 ). There is also no evidence of coverage of individuals representing the Egyptian or Coptic language. Similarly, Figure 1B of Pagani et al. ( 2015 ) depicts “East African” ancestry, similar to the ancestry of the Gumuz (who speak a Nilo-Saharan language), constituting < 10% of the Egyptians. Table 1 Ancestral composition based on autosomal data (Shriner et al., 2014 ) . Ancestry Egyptian (%) Gumuz (%) Amhara (%) Oromo (%) Wolayta (%) Ethiopian Somali (%) Somali (%) Ari Blacksmith (%) South Sudanese (%) CEU (%) Arabian 26.4 0 18.7 10.8 7.3 0 0 0 0 0 Berber 12.6 0 1.6 0 0 0 0 0 0 0 Cushitic 13.8 0 45.0 43.4 37.5 63.2 69.6 0 0 0 Levantine-Caucasian 25.0 0 0 0 0 0 0 0 0 9.4 Niger-Congo 5.4 0 0 0 0 0 0 0