The Divergence of Neandertal and Modern Human Y Chromosomes

Am J Hum Genet. 2016 Apr 7;98(4):728-34. doi: 10.1016/j.ajhg.2016.02.023.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cadherins / genetics
  • Chromosomes, Human, Y / genetics*
  • DNA / genetics
  • Genetic Variation
  • Histone Demethylases / genetics
  • Humans
  • Male
  • Minor Histocompatibility Antigens / genetics
  • Mutation, Missense
  • Neanderthals / genetics*
  • Pan troglodytes / genetics
  • Sequence Analysis, DNA
  • Spain
  • Ubiquitin Thiolesterase / genetics


  • Cadherins
  • Minor Histocompatibility Antigens
  • PCDH11Y protein, human
  • USP9Y protein, human
  • DNA
  • Histone Demethylases
  • KDM5D protein, human
  • Ubiquitin Thiolesterase