Human Biology Open Access Pre-Prints

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The polymorphic inversion on 17q21, that includes the MAPT gene, represents a unique locus in the human genome characterized by a large region with strong linkage disequilibrium. Two distinct haplotypes, H1 and H2, exist in modern humans, and H1 has been unequivocally related to several neurodegenerative disorders. Recent data indicates that recurrent inversions of this genomic region have occurred through primate evolution, with the H2 haplotype being the ancestral state. Neandertals harbored the H1 haplotype, however until now no data was available for the Denisova hominin. Neandertals and Denisovans are sister groups that share a common ancestor with modern humans. We analyzed the MAPT sequence and assessed the differences between modern humans, Neandertals, Denisovans, and great apes. Our analysis indicated that the Denisova hominin carried the H1 haplotype and the Neandertal and Denisova common ancestor probably shared the same subhaplotype (H1j). We also found 68 intronic variants within the MAPT gene, 23 exclusive to Denisova hominin, 6 limited to Neandertals and 24 exclusive to present-day humans. Our results reinforce previous data suggesting that the 17q21 inversion arose within the modern human lineage. The data also indicates that archaic hominins that coexisted in Eurasia probably shared the same MAPT subhaplotype, hat can be found in almost 2% of chromosomes from European ancestry.