An ancient evolutionary origin of genes associated with human genetic diseases.

An ancient evolutionary origin of genes associated with human genetic diseases.
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DOI:
10.1093/molbev/msn214
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发表时间:
2008-12
影响因子:
10.7
通讯作者:
Tautz D
Tautz D
中科院分区:
生物学1区
文献类型:
--
作者:
Domazet-Loso T;Tautz D

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人类基因组中的几千个基因与遗传性遗传疾病有关。这些基因中的大多数似乎是非必需基因(即,当失活时不是胚胎致死的),因此可以推测它们是向人类进化谱系中的晚期添加物。与这种预期相反,我们发现它们实际上在后生动物早期进化过程中出现的基因中明显过度表达。使用一种新的地层学方法,我们研究了这些基因在19个系统发育水平的进化出现。大多数疾病基因已经存在于真核生物的祖先中,而第二大数量的疾病基因是在多细胞生物进化的时候出现的。相反,哺乳动物谱系特有的基因是高度代表性不足。因此,与遗传疾病有关的基因并不是基因组中所有基因的随机子集,而是偏向于古老的基因。
Several thousand genes in the human genome have been linked to a heritable genetic disease. The majority of these appear to be nonessential genes (i.e., are not embryonically lethal when inactivated), and one could therefore speculate that they are late additions in the evolutionary lineage toward humans. Contrary to this expectation, we find that they are in fact significantly overrepresented among the genes that have emerged during the early evolution of the metazoa. Using a phylostratigraphic approach, we have studied the evolutionary emergence of such genes at 19 phylogenetic levels. The majority of disease genes was already present in the eukaryotic ancestor, and the second largest number has arisen around the time of evolution of multicellularity. Conversely, genes specific to the mammalian lineage are highly underrepresented. Hence, genes involved in genetic diseases are not simply a random subset of all genes in the genome but are biased toward ancient genes.
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