Woolly mammoths were among the most abundant cold adapted species during the Pleistocene. Their once large populations went extinct in two waves, an end-Pleistocene extinction of continental populations followed by the mid-Holocene extinction of relict populations on St. Paul Island ∼5,600 years ago and Wrangel Island ∼4,000 years ago. Wrangel Island mammoths experienced an episode of rapid demographic decline coincident with their isolation, leading to a small population, reduced genetic diversity, and the fixation of putatively deleterious alleles, but the functional consequences of these processes are unclear. Here we show that a Wrangel Island mammoth genome had many putative deleterious mutations that are predicted to cause diverse behavioral and developmental defects. Resurrection and functional characterization of several genes from the Wrangel Island mammoth carrying putatively deleterious substitutions identified both loss and gain of function mutations in genes associated with developmental defects (HYLS1), oligozoospermia and reduced male fertility (NKD1), diabetes (NEUROG3), and the ability to detect floral scents (OR5A1). These data suggest that at least one Wrangel Island mammoth may have suffered adverse consequences from reduced population size and isolation.

中文翻译：

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弗兰格尔岛猛mm象的基因组中有害遗传变异的功能结构。

羊毛猛ma象是更新世期间适应能力最强的物种之一。他们曾经的大种群灭绝了两波，大陆种群的更新世末期灭绝，然后是圣保罗岛（约5600年前）和弗兰格尔岛（约4000年前）的遗迹种群的全新世中期灭绝。弗兰格尔岛的猛mm象经历了人口快速下降的事件，这与它们的孤立相伴，导致人口少，遗传多样性减少和假定有害的等位基因的固定，但是这些过程的功能后果尚不清楚。在这里，我们表明，弗兰格尔岛的猛mm象基因组具有许多推定的有害突变，预计会导致多种行为和发育缺陷。弗兰格尔岛猛mm象的一些带有推定有害取代的基因的复活和功能表征鉴定了与发育缺陷（HYLS1），少精子症和雄性不育（NKD1），糖尿病（NEUROG3）相关的基因的功能突变的丧失和获得。能够检测花香（OR5A1）。这些数据表明，至少一个Wrangel岛猛ma象可能因种群数量减少和孤立而遭受了不利后果。