title: The Divergence of Neandertal and Modern Human Y Chromosomes.
abstract: Sequencing the genomes of extinct hominids has reshaped our understanding of modern human origins. Here, we analyze ∼120 kb of exome-captured Y-chromosome DNA from a Neandertal individual from El Sidrón, Spain. We investigate its divergence from orthologous chimpanzee and modern human sequences and find strong support for a model that places the Neandertal lineage as an outgroup to modern human Y chromosomes-including A00, the highly divergent basal haplogroup. We estimate that the time to the most recent common ancestor (TMRCA) of Neandertal and modern human Y chromosomes is ∼588 thousand years ago (kya) (95% confidence interval [CI]: 447-806 kya). This is ∼2.1 (95% CI: 1.7-2.9) times longer than the TMRCA of A00 and other extant modern human Y-chromosome lineages. This estimate suggests that the Y-chromosome divergence mirrors the population divergence of Neandertals and modern human ancestors, and it refutes alternative scenarios of a relatively recent or super-archaic origin of Neandertal Y chromosomes. The fact that the Neandertal Y we describe has never been observed in modern humans suggests that the lineage is most likely extinct. We identify protein-coding differences between Neandertal and modern human Y chromosomes, including potentially damaging changes to PCDH11Y, TMSB4Y, USP9Y, and KDM5D. Three of these changes are missense mutations in genes that produce male-specific minor histocompatibility (H-Y) antigens. Antigens derived from KDM5D, for example, are thought to elicit a maternal immune response during gestation. It is possible that incompatibilities at one or more of these genes played a role in the reproductive isolation of the two groups.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: flmendez@stanford.edu.
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Mendez
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA; Program in Biomedical Informatics, Stanford University, Stanford, CA 94305, USA.
authors.forename: G David
authors.initials: GD
authors.lastname: Poznik
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig 04103, Germany.
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellano
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA. Electronic address: cdbustam@stanford.edu.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Bustamante
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics*; D004247:DNA / Q000235:genetics; D014644:Genetic Variation; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D020125:Mutation, Missense; D059125:Neanderthals / Q000235:genetics*; D002679:Pan troglodytes / Q000235:genetics; D000091363:Protocadherins; D017422:Sequence Analysis, DNA; D013030:Spain; D043222:Ubiquitin Thiolesterase / Q000235:genetics
chemical_list: D015820:Cadherins; D015778:Minor Histocompatibility Antigens; C468654:PCDH11Y protein, human; D000091363:Protocadherins; C481724:USP9Y protein, human; D004247:DNA; D056466:Histone Demethylases; C095561:KDM5D protein, human; D043222:Ubiquitin Thiolesterase