Early evolutionary history and genomic features of gene duplicates in the human genome.
Early evolutionary history and genomic features of gene duplicates in the human genome.
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DOI：
10.1186/s12864-015-1827-3
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发表时间：
2015-08-20
期刊：
影响因子：
4.4
通讯作者：
Katju V
中科院分区：
文献类型：
--
作者：
Bu L;Katju V
自从近十年来基于阵列和靶向的下一代测序方法的发展以来，人类基因重复一直是密集研究的焦点。这些研究主要集中在从种群基因组的角度确定现存的拷贝数变异，但缺乏一个强大的进化框架来阐明早期的结构和基因组特征的基因重复在出现和随后的演变随着年龄的增长。我们分析了184个基因重复对，这些基因重复对包括人类基因组草图中具有10%或更少同义序列分歧的小基因家族。人类基因复制主要来源于DNA介导的事件，以染色体内拷贝的形式以正向或反向方向占据基因组。旁系同源物在常染色体上的分布遵循随机预期，而在性染色体上的分布则显著丰富。此外，人类基因重复序列沿染色体长度呈现出沿着倾斜的分布梯度，在着丝粒周围区域具有显著的聚类。令人惊讶的是，尽管人类基因的平均长度很大，但大多数现存的重复（83%）是完全重复的，其中祖先拷贝的整个ORF是重复的。完全重复的优势与36 kb的极大中值重复跨度雅阁，这提高了完整捕获祖先ORF的概率。随着进化年龄的增加，人类旁系同源物表现出（i）染色体内旁系同源物的频率和（ii）完全重复的比例下降。这些变化可能反映了某些类别的重复和/或纯化选择的作用的存活率较低。由RNA介导的事件引起的重复包括所有人类旁系同源物的一小部分（11.4%），并且在重复的较老进化队列中更多。结构相似的程度，基因组位置和重复跨度似乎影响人类基因组中旁系同源物的长期维持。人类基因组中的中值重复跨度远远超过C。线虫和酵母，并且可能导致相对于结构异质性重复（部分和嵌合）的完全重复的高流行率。调控序列与外显子-内含子结构变化在人类旁系同源基因获得新功能中的相对作用仍有待确定。本文的在线版本（doi：10.1186/s12864-015-1827-3）包含补充材料，可供授权用户使用。
Human gene duplicates have been the focus of intense research since the development of array-based and targeted next-generation sequencing approaches in the last decade. These studies have primarily concentrated on determining the extant copy-number variation from a population-genomic perspective but lack a robust evolutionary framework to elucidate the early structural and genomic characteristics of gene duplicates at emergence and their subsequent evolution with increasing age. We analyzed 184 gene duplicate pairs comprising small gene families in the draft human genome with 10 % or less synonymous sequence divergence. Human gene duplicates primarily originate from DNA-mediated events, taking up genomic residence as intrachromosomal copies in direct or inverse orientation. The distribution of paralogs on autosomes follows random expectations in contrast to their significant enrichment on the sex chromosomes. Furthermore, human gene duplicates exhibit a skewed gradient of distribution along the chromosomal length with significant clustering in pericentromeric regions. Surprisingly, despite the large average length of human genes, the majority of extant duplicates (83 %) are complete duplicates, wherein the entire ORF of the ancestral copy was duplicated. The preponderance of complete duplicates is in accord with an extremely large median duplication span of 36 kb, which enhances the probability of capturing ancestral ORFs in their entirety. With increasing evolutionary age, human paralogs exhibit declines in (i) the frequency of intrachromosomal paralogs, and (ii) the proportion of complete duplicates. These changes may reflect lower survival rates of certain classes of duplicates and/or the role of purifying selection. Duplications arising from RNA-mediated events comprise a small fraction (11.4 %) of all human paralogs and are more numerous in older evolutionary cohorts of duplicates. The degree of structural resemblance, genomic location and duplication span appear to influence the long-term maintenance of paralogs in the human genome. The median duplication span in the human genome far exceeds that in C. elegans and yeast and likely contributes to the high prevalence of complete duplicates relative to structurally heterogeneous duplicates (partial and chimeric). The relative roles of regulatory sequence versus exon-intron structure changes in the acquisition of novel function by human paralogs remains to be determined. The online version of this article (doi:10.1186/s12864-015-1827-3) contains supplementary material, which is available to authorized users.