Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
Institute for Diabetes and Obesity, Helmholtz Zentrum München, German Research Center for Environmental Health, Parkring 13, 85748 Garching, Germany.
Sci Adv. 2017 Jul 12;3(7):e1602878. doi: 10.1126/sciadv.1602878. eCollection 2017 Jul.
Mitochondrial uncoupling protein 1 (UCP1) is essential for nonshivering thermogenesis in brown adipose tissue and is widely accepted to have played a key thermoregulatory role in small-bodied and neonatal placental mammals that enabled the exploitation of cold environments. We map sequences from 133 mammals onto a species tree constructed from a ~51-kb sequence alignment and show that inactivating mutations have occurred in at least 8 of the 18 traditional placental orders, thereby challenging the physiological importance of UCP1 across Placentalia. Selection and timetree analyses further reveal that inactivations temporally correspond with strong secondary reductions in metabolic intensity in xenarthrans and pangolins, or in six other lineages coincided with a ~30 million-year episode of global cooling in the Paleogene that promoted sharp increases in body mass and cladogenesis evident in the fossil record. Our findings also demonstrate that members of various lineages (for example, cetaceans, horses, woolly mammoths, Steller's sea cows) evolved extreme cold hardiness in the absence of UCP1-mediated thermogenesis. Finally, we identify inactivation as a historical contingency that is linked to the current low species diversity of clades lacking functional UCP1, thus providing the first evidence for species selection related to the presence or absence of a single gene product.
解偶联蛋白 1（UCP1）对于棕色脂肪组织的非颤抖性产热至关重要，并且被广泛认为在体型较小和新生胎盘哺乳动物中发挥了关键的体温调节作用，使它们能够利用寒冷环境。我们将来自 133 种哺乳动物的序列映射到从一个约 51-kb 序列比对构建的种系树上，并表明至少有 8 个传统胎盘类群中的 18 个发生了失活突变，从而挑战了 UCP1 在胎盘类中的生理重要性。选择和时间树分析进一步表明，失活在有袋动物和穿山甲中与代谢强度的强烈次生降低，或在其他六个谱系中与古近纪约 3000 万年的全球冷却事件同时发生，这促进了化石记录中明显的体重增加和分类群分化。我们的研究结果还表明，来自不同谱系的成员（例如，鲸鱼、马、猛犸象、斯特勒海牛）在缺乏 UCP1 介导的产热的情况下进化出了对极寒的耐寒性。最后，我们确定失活是一种历史偶然事件，与缺乏功能性 UCP1 的类群当前的低物种多样性有关，从而为与单个基因产物的存在或缺失相关的物种选择提供了第一个证据。
