Mutation pattern variation among regions of the primate genome
Mutation pattern variation among regions of the primate genome
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DOI：
10.1007/pl00006223
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发表时间：
1997-09-01
影响因子：
3.9
通讯作者：
Li, WH
中科院分区：
文献类型：
--
作者：
Casane, D;Boissinot, S;Li, WH
我们对人类、猩猩、狒狒和疣猴的三个乙酰氨基琥珀酸合成酶加工假基因（Psi AS-A1、Psi AS-A3、Psi AS-3）及其非编码侧翼序列进行了测序。我们的数据显示，这些假基因在旧世界和新世界猴谱系分化后被整合到旧世界猴的基因组中。这些假基因侧翼区显示出可变的突变率和模式。G/C对A/T的突变率（u）的变化可以解释平衡时GC含量的不相等：在假基因Psi AS-A1、Psi AS-A3和Psi AS-3侧翼区中分别为34.9%、36.9%和41.7%。A/T到G/C的突变率（v）似乎稳定，并且在Psi AS-A1、Psi AS-A3和Psi AS-3的侧翼区域中u/v比分别等于1.9、1.7和1.4。这些突变率的"区域性"差异也影响了假基因的进化。在每种情况下，u/v比大于1.0，如所预期的，富含GC的假基因中的总体突变率高于其GC贫乏的侧翼区。此外，还发现了一种"序列效应"。在所研究的三种情况下，假基因中的u和v比其侧翼区高（至少20%）-即，假基因表现为嵌入"冷"区域的突变"热点"。这一观察结果可能部分与假基因侧翼区是长期存在的不受约束的DNA序列这一事实有关，而假基因仅在大约3000万至4000万年前才被解除对其编码功能的选择。我们怀疑，相对更多的突变位点保持不变，在进化过程中的caseinosuccinate基因是能够改变的假基因，这些网站被淘汰或罕见的侧翼地区，已缺乏强选择性的限制，在一个更长的时间。我们的研究结果揭示了（1）调节自发突变率的因素的多样性和（2）序列的基因组位置对其进化的影响。
We sequenced three argininosuccinate-synthetase-processed pseudogenes (Psi AS-A1, Psi AS-A3, Psi AS-3) and their noncoding flanking sequences in human, orangutan, baboon, and colobus. Our data showed that these pseudogenes were incorporated into the genome of the Old World monkeys after the divergence of the Old World and New World monkey lineages. These pseudogene flanking regions show variable mutation rates and patterns, The variation in the G/C to A/T mu ration rate (u) can account for the unequal GC contents at equilibrium: 34.9, 36.9, and 41.7% in the pseudogene Psi AS-A1, Psi AS-A3, and Psi AS-3 flanking regions, respectively. The A/T to G/C mutation rate (v) seems stable and the u/v ratios equal 1.9, 1.7, and 1.4 in the flanking regions of Psi AS-A1, Psi AS-A3, and Psi AS-3, respectively. These ''regional'' variations of the mutation rate affect the evolution of the pseudogenes, too. The ratio u/v being greater than 1.0 in each case, the overall mutation rate in the GC-rich pseudogenes is, as expected, higher than in their GC-poor flanking regions. Moreover, a ''sequence effect'' has been found. In the three cases examined u and v are higher (at least 20%) in the pseudogene than in its flanking region-i.e., the pseudogene appears as mutation ''hot'' spots embedded in ''cold'' regions. This observation could be partly linked to the fact that the pseudogene flanking regions are longstanding unconstrained DNA sequences, whereas the pseudogenes were relieved of selection on their coding functions only around 30-40 million years ago. We suspect that relatively more mutable sites maintained unchanged during the evolution of the argininosuccinate gene are able to change in the pseudogenes, such sites being eliminated or rare in the flanking regions which have been void of strong selective constraints over a much longer period. Our results shed light on (1) the multiplicity of factors that tune the spontaneous mutation rate and (2) the impact of the genomic position of a sequence on its evolution.