Vowles Edward J, Amos William
Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
Mol Biol Evol. 2006 Mar;23(3):598-607. doi: 10.1093/molbev/msj065. Epub 2005 Nov 21.
Surveys of variability of homologous microsatellite loci among species reveal an ascertainment bias for microsatellite length where microsatellite loci isolated in one species tend to be longer than homologous loci in related species. Here, we take advantage of the availability of aligned human and chimpanzee genome sequences to compare length difference of homologous microsatellites for loci identified in humans to length difference for loci identified in chimpanzees. We are able to quantify ascertainment bias for a range of motifs and microsatellite lengths. Because ascertainment bias should not exist if a microsatellite selected in one species is as likely to be longer as it is to be shorter than its homologue, we propose that the nature of ascertainment bias can provide evidence for understanding how microsatellites evolve. We show that bias is greater for longer microsatellites but also that many long microsatellites have short homologues. These results are consistent with the notion that growth of long microsatellites is constrained by an upper length boundary that, when reached, sometimes results in large deletions. By evaluating ascertainment bias separately for interrupted and uninterrupted repeats we also show that long microsatellites tend to become interrupted, thereby contributing a second component of ascertainment bias. Having accounted for ascertainment bias, in agreement with results published elsewhere, we find that microsatellites in humans are longer on average than those in chimpanzees. This length difference is similar among repeat motifs but surprisingly comprises two roughly equal components, one associated with the repeats themselves and one with the flanking sequences. The differences we find can only be explained if microsatellites are both evolving directionally under a biased mutation process and are doing so at different rates in different closely related species.
对物种间同源微卫星位点变异性的调查揭示了微卫星长度的确定偏差，即在一个物种中分离出的微卫星位点往往比相关物种中的同源位点更长。在这里，我们利用人类和黑猩猩基因组序列比对的可用性，比较人类中鉴定出的位点的同源微卫星长度差异与黑猩猩中鉴定出的位点的长度差异。我们能够量化一系列基序和微卫星长度的确定偏差。由于如果在一个物种中选择的微卫星与其同源物相比，变长的可能性与变短的可能性相同，则不应存在确定偏差，因此我们提出确定偏差的性质可以为理解微卫星如何进化提供证据。我们表明，较长微卫星的偏差更大，但许多长微卫星也有短同源物。这些结果与以下观点一致，即长微卫星的增长受到长度上限的限制，当达到该上限时，有时会导致大量缺失。通过分别评估间断和不间断重复序列的确定偏差，我们还表明长微卫星倾向于变得间断，从而导致确定偏差的第二个组成部分。在考虑了确定偏差之后，与其他地方发表的结果一致，我们发现人类中的微卫星平均比黑猩猩中的微卫星长。这种长度差异在重复基序中相似，但令人惊讶的是它由两个大致相等的部分组成，一个与重复序列本身相关，另一个与侧翼序列相关。只有当微卫星在有偏差的突变过程中定向进化并且在不同的密切相关物种中以不同的速率进化时，我们发现差异才能得到解释。
