Positive selection on protein-length in the evolution of a primate sperm ion channel
Positive selection on protein-length in the evolution of a primate sperm ion channel
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DOI：
10.1073/pnas.2033555100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Zhang, JZ
中科院分区：
文献类型：
--
作者：
Podlaha, O;Zhang, JZ
在许多基因中已经证明了优势点替换的正达尔文选择。我们在这里提供的经验证据，第一次，积极的选择也可以作用于插入/缺失（indel）取代蛋白质的进化。CATSPER 1是一种仅在哺乳动物精子尾部质膜中发现的电压门控钙通道，它对精子运动至关重要。我们测定了15种灵长类动物CATSPER 1基因第一外显子的DNA序列，该基因编码约400个氨基酸的胞内N端区域。这些序列表现出非常高的插入缺失频率。然而，所有插入缺失的长度都是3 nt的倍数（3 n插入缺失），并且不破坏ORF。CATSPER 1中每年每个位点的indel替换数量是从两个大规模灵长类动物基因组比较计算的相应速率的5至8倍，这代表了indel替换的中性速率。此外，CATSPER 1插入缺失比中性插入缺失长得多。这些观察结果强烈表明，正选择一直在促进CATSPER 1外显子1中indel突变的固定。在某些离子通道中已经显示，N末端区域的长度影响通道失活的速率。这一发现表明，检测到的选择可能与CATSPER 1通道的调节有关，CATSPER 1通道可以影响精子活力，这是精子竞争的重要决定因素。
Positive Darwinian selection on advantageous point substitutions has been demonstrated in many genes. We here provide empirical evidence, for the first time, that positive selection can also act on insertion/deletion (indel) substitutions in the evolution of a protein. CATSPER1 is a voltage-gated calcium channel found exclusively in the plasma membrane of the mammalian sperm tail and it is essential for sperm motility. We determined the DNA sequences of the first exon of the CATSPER1 gene from 15 primates, which encodes the intracellular N terminus region of approximate to400 aa. These sequences exhibit an excessively high frequency of indels. However, all indels have lengths that are multiples of 3 nt (3n indels) and do not disrupt the ORF. The number of indel substitutions per site per year in CATSPER1 is five to eight times the corresponding rates calculated from two large-scale primate genomic comparisons, which represent the neutral rate of indel substitutions. Moreover, CATSPER1 indels are considerably longer than neutral indels. These observations strongly suggest that positive selection has been promoting the fixation of indel mutations in CATSPER1 exon 1. It has been shown in certain ion channels that the length of the N terminus region affects the rate of channel inactivation. This finding suggests that the selection detected may be related to the regulation of the CATSPER1 channel, which can affect sperm motility, an important determinant in sperm competition.