Mendez Fernando L, Poznik G David, Castellano Sergi, Bustamante Carlos D
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Department of Genetics, Stanford University, Stanford, CA 94305, USA; Program in Biomedical Informatics, Stanford University, Stanford, CA 94305, USA.
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.
对已灭绝的古人类基因组进行测序，重塑了我们对现代人类起源的理解。在此，我们分析了来自西班牙埃尔西多龙的一名尼安德特人的约120 kb外显子捕获Y染色体DNA。我们研究了它与直系同源黑猩猩和现代人类序列的差异，发现有力支持了一种模型，该模型将尼安德特人谱系定位为现代人类Y染色体（包括高度分化的基础单倍群A00）的外类群。我们估计，尼安德特人和现代人类Y染色体的最近共同祖先时间（TMRCA）约为58.8万年前（kya）（95%置信区间[CI]：44.7 - 80.6 kya）。这比A00与其他现存现代人类Y染色体谱系的TMRCA长约2.1倍（95% CI：1.7 - 2.9）。这一估计表明，Y染色体的分化反映了尼安德特人和现代人类祖先的种群分化，并且反驳了尼安德特人Y染色体相对近期或超古老起源的其他假设。我们所描述的尼安德特人Y染色体从未在现代人类中被观察到这一事实表明，该谱系很可能已经灭绝。我们确定了尼安德特人和现代人类Y染色体之间的蛋白质编码差异，包括对PCDH11Y、TMSB4Y、USP9Y和KDM5D的潜在有害变化。其中三个变化是产生男性特异性次要组织相容性（H - Y）抗原的基因中的错义突变。例如，源自KDM5D的抗原被认为在妊娠期间引发母体免疫反应。这些基因中一个或多个的不相容性有可能在两组的生殖隔离中起作用。
