Strong mutational bias toward deletions in the Drosophila melanogaster genome is compensated by selection.
Strong mutational bias toward deletions in the Drosophila melanogaster genome is compensated by selection.
复制标题
DOI：
10.1093/gbe/evt021
复制
发表时间：
2013
影响因子：
3.3
通讯作者：
Kondrashov AS
中科院分区：
文献类型：
--
作者：
Leushkin EV;Bazykin GA;Kondrashov AS
插入和缺失（统称为插入缺失）显然对基因组进化具有重大影响。然而，在获得有关插入缺失多态性的大规模数据之前，很难估计选择对插入缺失突变的强度。在这里，我们分析了果蝇基因组不同区室的插入缺失多态性和分歧：外显子、不同长度的内含子和基因间区域。低频多态性数据表明，每个单核苷酸替换会发生 0.036-0.039 个短（1-30 nt）插入突变和 0.085-0.092 个短缺失突变，平均长度分别为 3.23 和 4.78。短缺失突变超过短插入突变意味着这些长度的插入缺失突变应导致每个单核苷酸替换丢失约 0.30 nt。然而，多态性和分歧数据表明，这种删除偏差几乎完全被选择所补偿：负选择对删除的抵抗力更强，而插入更有可能受到正选择的青睐。在外显子、长内含子和基因间区域的框内低频多态性突变中，选择阻止了更大比例的缺失（80-87%，取决于区室的类型）而不是插入（70-82%）或单核苷酸取代（49-73%）达到高频率。短内含子中相应的分数最低：分别为 66%、47% 和 15%，与其中最弱的选择性约束一致。 McDonald-Kreitman 检验表明，黑腹果蝇近期进化中固定的 32-46% 的缺失和 60-73% 的插入是适应性的，而单核苷酸替换的这一比例仅为 0-29%。
Insertions and deletions (collectively indels) obviously have a major impact on genome evolution. However, before large-scale data on indel polymorphism became available, it was difficult to estimate the strength of selection acting on indel mutations. Here, we analyze indel polymorphism and divergence in different compartments of the Drosophila melanogaster genome: exons, introns of different lengths, and intergenic regions. Data on low-frequency polymorphisms indicate that 0.036–0.039 short (1–30 nt) insertion mutations and 0.085–0.092 short deletion mutations, with mean lengths 3.23 and 4.78, respectively, occur per single-nucleotide substitution. The excess of short deletion over short insertion mutations implies that indel mutations of these lengths should lead to a loss of approximately 0.30 nt per single-nucleotide replacement. However, polymorphism and divergence data show that this deletion bias is almost completely compensated by selection: Negative selection is stronger against deletions, whereas insertions are more likely to be favored by positive selection. Among the inframe low-frequency polymorphic mutations in exons, long introns, and intergenic regions, selection prevents a larger fraction of deletions (80–87%, depending on the type of the compartment) than of insertions (70–82%) or single-nucleotide substitutions (49–73%), from reaching high frequencies. The corresponding fractions were the lowest in short introns: 66%, 47%, and 15%, respectively, consistent with the weakest selective constraint in them. The McDonald–Kreitman test shows that 32–46% of the deletions and 60–73% of the insertions that were fixed in the recent evolution of D. melanogaster are adaptive, whereas this fraction is only 0–29% for single-nucleotide substitutions.
登录
查看更多内容
影响因子：
64.8
作者：
Clark, Andrew G.;Eisen, Michael B.;MacCallum, Iain
通讯作者：
MacCallum, Iain
FlyBase：十几个基因组。
影响因子：
14.9
作者：
Crosby MA;Goodman JL;Strelets VB;Zhang P;Gelbart WM;FlyBase Consortium
通讯作者：
FlyBase Consortium
影响因子：
12.3
作者：
Huse SM;Huber JA;Morrison HG;Sogin ML;Welch DM
通讯作者：
Welch DM
影响因子：
7
作者：
Heger, Andreas;Ponting, Chris P.
通讯作者：
Ponting, Chris P.
影响因子：
10.7
作者：
Blumenstiel, JP;Hartl, DL;Lozovsky, ER
通讯作者：
Lozovsky, ER