Strong Selection During the Last Millennium for African Ancestry in the Admixed Population of Madagascar
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ARTICLE DOI: 10.1038/s41467-018-03342-5 OPEN Strong selection during the last millennium for African ancestry in the admixed population of Madagascar Denis Pierron1, Margit Heiske1, Harilanto Razafindrazaka2,1, Veronica Pereda-loth1, Jazmin Sanchez1, Omar Alva1, Amal Arachiche1, Anne Boland3, Robert Olaso3, Jean-Francois Deleuze3, Francois-Xavier Ricaut1, Jean-Aimé Rakotoarisoa4, Chantal Radimilahy4, Mark Stoneking5 & Thierry Letellier1 1234567890():,; While admixed populations offer a unique opportunity to detect selection, the admixture in most of the studied populations occurred too recently to produce conclusive signals. By contrast, Malagasy populations originate from admixture between Asian and African popu- lations that occurred ~27 generations ago, providing power to detect selection. We analyze local ancestry across the genomes of 700 Malagasy and identify a strong signal of recent positive selection, with an estimated selection coefficient >0.2. The selection is for African ancestry and affects 25% of chromosome 1, including the Duffy blood group gene. The null allele at this gene provides resistance to Plasmodium vivax malaria, and previous studies have suggested positive selection for this allele in the Malagasy population. This selection event also influences numerous other genes implicated in immunity, cardiovascular diseases, and asthma and decreases the Asian ancestry genome-wide by 10%, illustrating the role played by selection in recent human history. 1 Laboratoire d’Anthropologie Moleculairé et Imagerie de Synthese,̀ UMR 5288 CNRS, Universitéde Toulouse, 31073 Toulouse, France. 2 Aix Marseille Univ., CNRS, EFS, ADES, Marseille, France. 3 Commissariat à l’Energie Atomique, Institut Génomique, Centre National de Génotypage, 91000 Evry, France. 4 Institut de Civilisations/Musée d’Art et d’Archeologie,́ Université d’Antananarivo, 101 Antananarivo, Madagascar. 5 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany. Correspondence and requests for materials should be addressed to D.P. (email: [email protected]) NATURE COMMUNICATIONS | (2018) 9:932 | DOI: 10.1038/s41467-018-03342-5 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-03342-5 peaking an Austronesian language and living <400 km from As the admixture in Madagascar occurred ~27 generations the African coast, the origins and history of the Malagasy ago4 and involves populations that diverged at least 50 000 years S 14 populations have long been a mystery. Recently, combined ago , the admixture approach should be informative, as ancestry advances in archeology, genetics, and linguistics, along with can be confidently assigned and there has been ample time for extensive sampling across Malagasy populations, provide a better selection to generate a detectable signal. Indeed, signals of positive – understanding of the settlement history1 3. Indeed, Malagasy selection have been detected in the Malagasy populations2, 15.In populations originate from an admixture between populations particular Hodgson et al.15 showed that under neutrality the high with Austronesian and Bantu genetic backgrounds that occurred frequency of the African Duffy null allele in the Malagasy ~27 generations ago4. Linguistic and genetic evidence converge population16 is incompatible with the admixture level measured on a model of Bantu populations migrating across the Mozam- in Madagascar; this allele is associated with protection against bique channel from the east coast of Africa, while the Aus- Plasmodium vivax malaria and is fixed (or nearly so) in Africa but tronesian population came 7000 km across the Indian Ocean essentially absent outside Africa17. This study analyzed variation from south Borneo3. at a single single-nucleotide polymorphism (SNP) in two Mala- The meetings of these two populations led to both cultural and gasy populations15, here, to further investigate this as well as genetic mixture, generating a patchwork of cultural and genetic other potential signals of recent positive selection, we performed a traits across Madagascar. For example, while the language is genome-wide analysis of local ancestry across the genomes of 700 mostly Austronesian, the musical instruments are mostly from Malagasy based on a sampling from 257 villages from all across Africa5, and Austronesian genetic ancestry is higher in the central Madagascar4.Wefind that the Malagasy genome has been shaped highlands than elsewhere4. The cultural and genomic landscape by a selection event, probably corresponding to selection for the of Madagascar mostly reflects historic events of contact between Duffy null allele, that is exceptional in terms of strength (s > 0.2) groups followed by random fluctuations. However, some cultural and overall impact (~25% of the chromosome is in the selected aspects, such as farming, might reflect cultural adaptation to region). Moreover, this selection has been ongoing over the last environmental constraints, as the adoption of crops and farming millennium, showing that recent selection does influence human practices varied according to environmental circumstances6. Here populations. we test the hypothesis that in addition to culture adaptation, genetic adaptation has also played a role in the history of Madagascar, by examining the distribution of Austronesian- Results related and Bantu-related genetic ancestry across Malagasy Local ancestry estimation. To look for signals of recent positive genomes. selection, we used the mixed ancestry of Malagasy genomes and In the absence of selection, the ancestry associated with each searched for genomic regions with unusually high or low levels of parental group of an admixed population is expected to be dis- African or Asian ancestry. To measure the Asian and African tributed more or less evenly across the genome; significant contribution across the Malagasy genome, we used the Efficient departures from this expected random distribution are thus a Local Ancestry Inference (ELAI) algorithm to perform local potential signal of selection. This approach has been used to ancestry inference on 1.9 million SNPs genotyped in 700 indi- demonstrate the importance of “adaptive introgression” of genes 4 – viduals sampled from 257 villages across Madagascar . The between modern populations7 10 or even between archaic – average Asian ancestry across individuals was 38.47 ± 3.0% per humans and modern populations11 13. However, detecting position across the genome, in agreement with previous admixture-related selection is problematic in modern populations studies2, 4, 15. where the admixture occurred only a few generations ago, as The distribution of the ancestry inference across each position there may not have been enough time for selection to generate a in the genome (Fig. 1) revealed a highly significant decrease in detectable signal in the distribution of ancestry across the gen- Asian ancestry (and corresponding increase in African ancestry) ome. For example, there is ongoing debate concerning results on chromosome 1 near the locus 1q23. The lowest Asian ancestry suggesting positive selection for African alleles at some loci in the in this region is 8.7%, corresponding to a deviation of 9.9 standard – − Americas7 9. deviations (SDs) from the mean and a p-value < 10 16 (Grubbs 12345678910111213141516171819202122 50 40 30 % of Asian ancestry 20 10 Chromosomic physical positions Fig. 1 Average Asian ancestry estimated using ELAI, across the 700 Malagasy individuals, for each position of each chromosome. In this analysis the African and Asian populations from the 1000 Genomes Project22 were used as proxies for the African and Asian ancestry in the Malagasy; the results from other reference populations are provided in Supplementary Figure, and using other approaches and reference populations in Supplementary Figures 2 and 3. Black lines represent a deviation of 3 SD from the mean and blue lines represent a deviation of 6 SD from the mean 2 NATURE COMMUNICATIONS | (2018) 9:932 | DOI: 10.1038/s41467-018-03342-5 | www.nature.com/naturecommunications NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-03342-5 ARTICLE = = tests for one outlier G 9.90, U 0.99995 computed on the 0.6 whole dataset and G = 10.00, U = 0.99971 on pruned dataset). A similar decrease in Asian ancestry was observed when different combinations of African and Asian populations were used as proxies (Supplementary Fig. 1), or different algorithms were used to infer local ancestry (Supplementary Fig. 2). This decrease in 0.4 Asian ancestry was also observed when applying an unsupervised global ancestry method (ADMIXTURE, k = 2) on various windows over the genome (Fig. 2). Thus, the decrease in Asian ancestry near locus 1q23 in the Malagasy is robust to the choice of reference populations or local ancestry algorithm. 0.2 Percentage of Asian component Selection analysis. We next used computer simulations15 to estimate the probability that genetic drift alone could produce such a low frequency (8.7%) of Asian ancestry. We carried out 0.0 “ ” one million simulations using a realistic model based on SD3 SD6 SD9 Whole Whole demographic parameters estimated from the same dataset. For CH1 genome this “realistic” model the date of admixture between Asian and Genomic regions African populations was based on previous estimations4 based on Fig. 2 Asian ancestry proportion of the Malagasy population by genomic ALDER18 and GLOBETROTTER19 and represents the starting region, based