Out of Africa and Back Again? Nov 25, 2016 20:43:35 GMT
Post by Admin on Nov 25, 2016 20:43:35 GMT
Figure 1. Map of samples and population structure of North Africa and neighboring populations.
Out of Africa and Back Again?
By sampling multiple populations along an approximate transect across North Africa, we were able to identify gradients in ancestry along an east-west axis (Figure 1 and Figure 2). Notably, even northwestern populations with very high proportions of Maghrebi ancestry, such as the Tunisians and Saharawi, still cluster with Out-of-Africa populations in the population structure analyses (Figure 1 (k = 2), Figure 2). This observation of clustering formed the basis for further analyses to distinguish between two alternative demographic models. First, North Africans could be closer to OOA populations due to extensive gene flow, likely from the Near East, over the past ∼50 Kya. Second, North Africans could be closer to OOA populations if the two groups had diverged more recently than either had split with sub-Saharan Africans.
We can reject a simple model of long-term continuous gene flow between the Near East and North Africa, as evidenced by clear geographic structure and non-zero Fst estimates. Fst estimates between the inferred Maghrebi cluster and sub-Saharan Africans are two to three-times greater than Fst between the Maghrebi and Europeans/Near Easterners ancestral clusters (Table S3). We then address whether this population structure was recent or ancient. Although Fst estimates from ascertained data may be biased, as rare alleles are under-represented in the site frequency spectrum, comparison of African-European Fst from resequencing data and the Affymetrix 500 K platform showed only a negligible difference . Assuming reasonable effective population sizes for North African Maghrebi and neighboring populations , we first showed that all North African populations are estimated to have diverged from OOA groups more than 12,000 ya (Figure 3). After accounting for putative recent admixture (Figure 1), the indigenous Maghrebi component (k-based) is estimated to have diverged from Near Eastern/Europeans between 18–38 Kya (Figure 3), under a range of Ne and k values. We hence suggest that the ancestral Maghrebi population separated from Near Eastern/Europeans prior to the Holocene, and that the Maghrebi populations do not represent a large-scale demic diffusion of agropastoralists from the Near East.
Figure 2. Multidimensional scaling components discriminating genetic clusters in Africa.
With model parameters for divergence approximately estimated, we then ask whether North African ancestral populations were part of the initial OOA exit and then returned to Africa , or if an in situ model of population persistence for the past 50 Kya is more likely (with variable episodes of migration from the Near East)? We can address this question only indirectly with contemporary samples; however, several auxiliary observations point toward the former hypothesis. Substantially elevated linkage disequilibrium in all of these North African population samples, compared to sub-Saharan populations , is consistent with a population bottleneck. Hellenthal et al.  also observed that the reduction in the number of haplotype founders required to reconstruct the Mozabite population, as compared to other African populations, could be explained by a population bottleneck. If North African ancestral populations persisted in situ, then we need to invoke two population bottlenecks, one in the ancestors of North Africans (including the Berbers) and one for OOA groups. Alternatively, the “OOA” bottleneck would need to occur in North Africa, rather than when groups moved out of the continent . The second possibility appears at odds with most published models of the movement of modern humans outside of Africa.
A scenario where North African Maghrebi ancestry is the result of in situ population absorbing Near Eastern migrants would likely need the following premises to explain the results here and elsewhere: a) an Out-of-Africa migration [concurrent with bottleneck] occurs 50–60 Kya, geographically dividing North African and Near Eastern populations; b) North Africans experience a separate bottleneck; c) gene flow maintains similarity between the two geographically distinct populations; d) the gene flow then ceases or slows roughly between 12–40 Kya in order to allow sufficiently distinct allele frequency distributions to form. In contrast, we find it more parsimonious to describe model where: a) an OOA migration occurs [concurrent with a bottleneck]; b) OOA populations and North Africans diverge between 12–40 Kya when a migration back-to-Africa occurs. These models should be further tested with genomic sequence data, which have better power to detect magnitude and timing of bottlenecks, and to estimate the true joint allele frequency spectrum.
Figure 3. Divergence time estimates among European, Maghrebi, and Near Eastern ancestral populations.
More recently, the substantial, east-to-west decline of Near Eastern ancestry (Figure 1A) could represent a defined migration associated with Arab conquest 1,400 ya or merely gene flow occurring gradually among neighboring populations along a North African | Arabian Peninsula transect. Although we observe a declining amount of Maghrebi ancestry from northwest-to-northeast, it is possible that other geographically North African samples (e.g. Egyptians further south than the sampled Siwa Oasis) do not conform to this geographic cline. Finally, we also observe European ancestry that is not clearly accounted for by the inclusion of a Near Eastern sample. Additional migration coming from Europe might be plausible, though the origin and the period where it took place cannot be determined with the present data. The less than 25% European ancestry in populations like Algerians and northern Moroccans could trace back to maritime migrations throughout the Mediterranean . Alternatively, the Qatari could represent a poor proxy for an Arabic source population, causing additional diversity to be assigned European (e.g. European ancestry tracts were not reliably assigned as European with PCADMIX).
In summary, although paleoanthropological evidence has established the ancient presence of anatomically modern humans in northern Africa prior to 60,000 ya , the simplest interpretation of our results is that the majority of ancestry in modern North Africans derives from populations outside of Africa, through at least two episodes of increased gene flow during the past 40,000 years (Figure 1, Figure 2, Figure 3).
Figure 4. Distribution of long segments that are identical by descent (IBD) for pairs of individuals.
Reconstructing Multiple Admixed Ancestries
Multiple local ancestry assignment methods, including PCADMIX, require thinning genotype datasets to remove alleles in high linkage disequilibrium between populations , ; this step discards information regarding haplotype patterns that tend to be more informative than genotypes when using data biased by SNP ascertainment . HAPMIX incorporates both LD information and uncertainty in phase inference for haplotypes , but the software is currently limited to a two-population model. Our ancestral proportions of European and sub-Saharan ancestry for many North Africans at k = 2 (Figure 1) are similar to those obtained with HAPMIX by Price et al.  for the HGDP Algerian Mozabites, assuming a two-population mixture of northern Europeans and Yoruba. However, our results show that increasing the number of possible ancestral populations reveals multiple, diverse ancestries (e.g. Maghrebi, Near Eastern, Nilotic) and that the proportion of sub-Saharan African assignment decreases as these other ancestries are accounted for. This decrease in assigned sub-Saharan ancestry in North African samples, from a k = 2 model, is consistent with an interpretation that Maghrebi or Near Eastern diversity that is not present in the panel populations is more likely to be assigned to the more diverse, Sub-Saharan African ancestry. Using a two-population admixture model, Price et al.  estimated the time of migration from sub-Saharan Africa into the Mozabites to have begun about 100 generations ago (or more). Our results suggest that sub-Saharan African and Maghreb admixture is considerably more recent, 24–41 generations ago (and even the upper 95% CI estimate under either model is 55ga, Table 1). The discrepancy between these two estimates may result from our incorporation of multiple source populations, our use of non-linear models to estimate migration timing and the elimination, in Price et al. , of individuals with megabase long African segments.
Figure 5. Correlation between ancestry proportions inferred from ADMIXTURE and PCADMIX.
Time of Migration Estimation
We use a two-population model of migration where we measure the number and length of migrant tracts observed in the admixed population. However, as argued earlier, North African populations have absorbed migrants from multiple episodes of migration. We use three- and four-population admixture deconvolution to identify the tracts from these separate migrations. One complication with this approach is the possibility that source populations that contribute migrants to North Africa are themselves exchanging migrants. For example, Near Eastern populations expanded into European continent during the Neolithic, and even an isolated population like the Spanish Basque may have genomic segments that trace back to the Neolithic expansion , . In this case, estimation of the time of migration of Arabic individuals into North Africa would be biased by Basque segments of Arab ancestry that were contributed by Europeans, but are locally assigned to Arabic ancestry. We confine our migration estimates to those from sub-Saharan populations into North Africans because there has likely been relatively little recent gene flow between sub-Saharan Africans and the European/Near Eastern populations. Moorjani et al.  present evidence for recent gene flow (<100 generations ago) from Africa to the Near East and Europe. But, they hypothesize it might be due to North African migrations, rather than sub-Saharan Africa.
Assuming a 30-year generation time , the proposed migration of sub-Saharans to southern Morocco at about 1,200 years ago coincides with the rise of the Ghana Empire, involved in the trans-Saharan slave trading, and the “Great Berber Uprising” which established Berber kingdoms throughout Morocco. We use a Bantu-speaking population from Kenya as a source population for this migration, as North African individuals with sub-Saharan ancestry appeared to be closer to the Luhya than the Nigerian Yoruba (Figure 1, Figure 2 and Figure S2). However, there are likely other western African populations genetically similar to Kenyan Bantu-speakers. We do not interpret this association as an explicit migration from Kenya to southern Morocco. We also use the length of Nilotic tracts in Egyptians to ask if sub-Saharan ancestry (apparent in Figure 1 and Figure 6) also appears to be a recent introduction. Under a pulse model of migration, a significant increase in gene flow likely occurred ∼700 ya, after the Arabic expansion into North Africa 1,400 ya. Our migration results are in agreement with previous studies based on mtDNA analysis where gene flow into eastern and western North Africa appeared to have different sub-Saharan population sources , .
Our genome-wide dense genotyping data from seven North African populations allow us to address outstanding questions regarding the origin and migration history of North Africa. We propose that present-day ancestry in North Africa is the result of at least three distinct episodes: ancient “back-to-Africa” gene flow prior to the Holocene, more recent gene flow from the Near East resulting in a longitudinal gradient, and limited but very recent migrations from sub-Saharan Africa. Population structure in North Africa is particularly complex, and future disease or phenotypic studies should carefully account for local demographic history. However, the rich history of gene flow can also help empower genome-wide association mapping via admixture mapping techniques . For example, the variable but relatively long haplotypes of sub-Saharan ancestry are amenable to admixture mapping approaches developed for African-American samples. In conclusion, North African populations retain a unique signature of early “Maghrebi” ancestry, but North African populations are not a homogenous group and most display varying combinations of five distinct ancestries.