Recent de novo origin of human protein-coding genes
Recent de novo origin of human protein-coding genes
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DOI：
10.1101/gr.095026.109
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发表时间：
2009-10-01
期刊：
影响因子：
7
通讯作者：
McLysaght, Aoife
中科院分区：
文献类型：
--
作者：
Knowles, David G.;McLysaght, Aoife
新基因的起源对进化创新极其重要。大多数新基因是通过复制或重组从现有基因中产生的。新基因起源于非编码DNA是非常罕见的，并且已知的真核生物的例子很少。我们提出的证据，从头起源的至少三个人类蛋白质编码基因，因为与黑猩猩的分歧。这些基因中的每一个在任何其他基因组中都没有蛋白质编码同源物，但得到了表达证据的支持，重要的是，蛋白质组学数据。这些基因在黑猩猩和猕猴中的缺失不能用测序缺口或注释错误来解释。高质量的序列数据表明，这些基因座是其他灵长类动物的非编码DNA。此外，黑猩猩，大猩猩，长臂猿和猕猴共享相同的禁用序列差异，支持的推断，祖先序列是非编码的替代可能性的平行基因失活在多个灵长类谱系。这些基因还没有很好的表征，但有趣的是，其中一个基因首先被确定为慢性淋巴细胞白血病中的上调基因。这是第一个证据，完全新的人类特异性蛋白质编码基因起源于祖先的非编码序列。我们估计，0.075%的人类基因可能是通过这种机制起源的，因此在24，000个蛋白质编码基因的基因组中，预计总共有18个这样的病例。
The origin of new genes is extremely important to evolutionary innovation. Most new genes arise from existing genes through duplication or recombination. The origin of new genes from noncoding DNA is extremely rare, and very few eukaryotic examples are known. We present evidence for the de novo origin of at least three human protein-coding genes since the divergence with chimp. Each of these genes has no protein-coding homologs in any other genome, but is supported by evidence from expression and, importantly, proteomics data. The absence of these genes in chimp and macaque cannot be explained by sequencing gaps or annotation error. High-quality sequence data indicate that these loci are noncoding DNA in other primates. Furthermore, chimp, gorilla, gibbon, and macaque share the same disabling sequence difference, supporting the inference that the ancestral sequence was noncoding over the alternative possibility of parallel gene inactivation in multiple primate lineages. The genes are not well characterized, but interestingly, one of them was first identified as an up-regulated gene in chronic lymphocytic leukemia. This is the first evidence for entirely novel human-specific protein-coding genes originating from ancestrally noncoding sequences. We estimate that 0.075% of human genes may have originated through this mechanism leading to a total expectation of 18 such cases in a genome of 24,000 protein-coding genes.