Occurrence and consequences of coding sequence insertions and deletions in mammalian genomes
Occurrence and consequences of coding sequence insertions and deletions in mammalian genomes
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DOI：
10.1101/gr.1977804
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发表时间：
2004-04-01
期刊：
影响因子：
7
通讯作者：
Copley, RR
中科院分区：
文献类型：
--
作者：
Taylor, MS;Ponting, CP;Copley, RR
核苷酸插入和缺失（indel）事件，连同取代，代表了基因进化的主要跨国过程。通过对来自人类、小鼠和大鼠的8148个正向缺失基因的比对，我们在啮齿动物蛋白编码序列中确定了1743个indel事件。使用人类作为外群体，我们重建了这些indel中的每一个的突变事件。总的来说，我们发现了过量的删除插入，特别是大鼠谱系（70%的过量）。序列滑动占至少52%的插入和38%的缺失。我们还评估了可识别的蛋白质结构对indels的选择性耐受性。跨膜结构域是最少的，并且低复杂性区域是最耐受的。插入缺失到已知蛋白质结构上的映射表明，结构核心对插入缺失的耐受性明显低于环区域。在插入事件附近存在CpG二核苷酸的特异性富集，并且插入和缺失在较高G+C含量的序列中更常见。
Nucleotide insertion and deletion (indel) events, together with substitutions, represent the major multinational processes of gene evolution. Through the alignment of 8148 orthologous genes from human, mouse, and rat, we have identified 1743 indel events within rodent protein-coding sequences. Using human as an out-group, we reconstructed the mutational event underlying each of these indels. Overall, we found an excess of deletions over insertions, particularly for the rat lineage (70% excess). Sequence slippage accounts for at least 52% of insertions and 38% of deletions. We have also evaluated the selective tolerance of identifiable protein structures to indels. Transmembrane domains are the least, and low complexity regions, the most tolerant. Mapping of indels onto known protein structures demonstrated that structural cores are markedly less tolerant to indels than are loop regions. There is a specific enrichment of CpG dinucleotides in close proximity to insertion events, and both insertions and deletions are more common in higher G+C content sequences.