Nature头条：基因组证明人如何成为人

　　

生物通报道：来自斯坦福大学医学院等处的研究人员通过对人类基因组进行生物信息学的筛查，以及比对其它动物的基因组，发现了500多个人类特有的缺失基因，这对于分析人类基因功能具有重要的意义。这一研究成果公布在Nature杂志上。

领导这一研究的是斯坦福大学David M. Kingsley，和Gill Bejerano，这两位科学家围绕基因功能研究，比如增强子研究，垃圾DNA等展开了多项重要的研究，获得了颇多成果。

基因表达是指DNA序列转录为信使RNA（messenger RNA，简称mRNA），而后再将mRNA翻译成蛋白质序列的过程。大多数基因的表达调控方式是转录水平上的——细胞不会浪费能量来产生它们不需要的mRNA和蛋白质，因此许多基因仅在特异的器官、组织或细胞中表达。目前科学家人类特有的遗传特征，也就是人类区别于其它动物所在并不是十分清楚。

在这篇文章中，研究人员将人类基因组与其它动物基因组进行了全基因比对，从中发现了500多个人类特有的缺失基因，这些缺失的基因是黑猩猩和其他动物之间高度保守的序列，这些序列有可能为人类生物学的独特之处做出贡献，是人之所以成为人的基因组变化。

所缺失的序列大部分位于基因组中的非编码区域，有趣的是，人类基因组中的缺失集中在神经发育和甾类激素信号作用中所涉及的基因附近，这与以前人们提出的观点是一致的，这说明关键发育控制基因附近的调控性变化在人类进化中可能扮演重要角色。研究人员还发现的人类特异性缺失的具体例子包括：影响阴茎解剖的一个缺失和另一个与脑子大小有关的缺失。

原文摘要：

Human-specific loss of regulatory DNA and the evolution of human-specific traits

Humans differ from other animals in many aspects of anatomy, physiology, and behaviour; however, the genotypic basis of most human-specific traits remains unknown1. Recent whole-genome comparisons have made it possible to identify genes with elevated rates of amino acid change or divergent expression in humans, and non-coding sequences with accelerated base pair changes2, 3, 4, 5. Regulatory alterations may be particularly likely to produce phenotypic effects while preserving viability, and are known to underlie interesting evolutionary differences in other species6, 7, 8. Here we identify molecular events particularly likely to produce significant regulatory changes in humans: complete deletion of sequences otherwise highly conserved between chimpanzees and other mammals. We confirm 510 such deletions in humans, which fall almost exclusively in non-coding regions and are enriched near genes involved in steroid hormone signalling and neural function. One deletion removes a sensory vibrissae and penile spine enhancer from the human androgen receptor (AR) gene, a molecular change correlated with anatomical loss of androgen-dependent sensory vibrissae and penile spines in the human lineage9, 10. Another deletion removes a forebrain subventricular zone enhancer near the tumour suppressor gene growth arrest and DNA-damage-inducible, gamma (GADD45G)11, 12, a loss correlated with expansion of specific brain regions in humans. Deletions of tissue-specific enhancers may thus accompany both loss and gain traits in the human lineage, and provide specific examples of the kinds of regulatory alterations6, 7, 8 and inactivation events13 long proposed to have an important role in human evolutionary divergence.