Podlaha Ondrej, Zhang Jianzhi
Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12241-6. doi: 10.1073/pnas.2033555100. Epub 2003 Oct 1.
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 approximately equal to 400 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.
在许多基因中，正向达尔文选择对有利的点突变已得到证实。我们首次在此提供实证证据，表明正向选择在蛋白质进化过程中也可作用于插入/缺失（indel）突变。CATSPER1是一种电压门控钙通道，仅存在于哺乳动物精子尾部的质膜中，对精子运动至关重要。我们测定了15种灵长类动物CATSPER1基因第一个外显子的DNA序列，该外显子编码约400个氨基酸的细胞内N端区域。这些序列显示出过高的indel频率。然而，所有indel的长度均为3个核苷酸的倍数（3n indel），且不破坏开放阅读框（ORF）。CATSPER1中每个位点每年的indel替换数是通过两次大规模灵长类基因组比较计算出的相应速率的五到八倍，这代表了indel替换的中性速率。此外，CATSPER1的indel比中性indel长得多。这些观察结果强烈表明，正向选择一直在促进CATSPER1外显子1中indel突变的固定。在某些离子通道中已表明，N端区域的长度会影响通道失活的速率。这一发现表明，检测到的选择可能与CATSPER1通道的调节有关，而CATSPER1通道可影响精子运动，这是精子竞争中的一个重要决定因素。
