Atypical at skew in Firmicute genomes results from selection and not from mutation.
Atypical at skew in Firmicute genomes results from selection and not from mutation.
复制标题
DOI：
10.1371/journal.pgen.1002283
复制
发表时间：
2011-09
期刊：
影响因子：
4.5
通讯作者：
Feil EJ
中科院分区：
文献类型：
--
作者：
Charneski CA;Honti F;Bryant JM;Hurst LD;Feil EJ
第二个宇称规则指出，如果在突变或选择中没有偏差，那么在每条DNA链中，互补碱基以大约相等的频率存在。然而，在细菌中，在复制前导链中通常存在过量的G（超过C）和少量过量的T（超过a）。低G+C厚壁菌门，如金黄色葡萄球菌，在前导链上显示过量的A超过T是不寻常的。由于突变已被确定为在各种细菌分类群中产生这种偏态的主要力量，这种异常被认为反映了厚壁菌基因组中不寻常的突变偏差。在这里，我们表明情况并非如此，突变偏倚不能解释在金黄色葡萄球菌中看到的非典型AT偏倚。首先，最近出现的基因间snp预测了经典复制衍生的T相对于A的平衡富集，这与观察到的相反。其次，预测处于弱净化选择的位点仅显示弱AT偏态。第三，AT歪斜主要与非同义的第一和第二密码子位点有关，并且与它们的意义方向有关，而不是它们位于哪个复制链上。我们发现，非典型的AT偏态是基因与复制叉共取向的强烈倾向的结果，加上选择性地避免终止密码子和昂贵的氨基酸，它们往往具有富含t的密码子。基因间序列的A多于T，而在突变平衡时，T的优势是预期的，这指出了一个可能的进一步未解决的选择偏倚的来源。当考虑单链DNA时，每个碱基的频率不一定要等于它的互补伙伴，例如a = T和G = C。对于前导链，通常情况下g比Cs更常见，Ts比As更常见。这种偏倚被广泛认为是由于复制过程中不同的突变偏倚引起的。厚壁菌门在前链上表现出对A的非典型偏好，而不是对T的非典型偏好，在这里，我们表明选择而不是突变可以解释这种例外。对于编码区的那些碱基，选择的作用是增加A在T上的频率，以避免终止密码子，并使用代谢便宜的氨基酸。因为基因不是随机定向的，这表现为A在前导链上的整体富集。此外，突变模式的直接检查与观察到的As富集不一致。奇怪的是，我们的数据还指出了同义位点和基因间位点选择的一个未解决的来源，这被广泛认为是中立的。
The second parity rule states that, if there is no bias in mutation or selection, then within each strand of DNA complementary bases are present at approximately equal frequencies. In bacteria, however, there is commonly an excess of G (over C) and, to a lesser extent, T (over A) in the replicatory leading strand. The low G+C Firmicutes, such as Staphylococcus aureus, are unusual in displaying an excess of A over T on the leading strand. As mutation has been established as a major force in the generation of such skews across various bacterial taxa, this anomaly has been assumed to reflect unusual mutation biases in Firmicute genomes. Here we show that this is not the case and that mutation bias does not explain the atypical AT skew seen in S. aureus. First, recently arisen intergenic SNPs predict the classical replication-derived equilibrium enrichment of T relative to A, contrary to what is observed. Second, sites predicted to be under weak purifying selection display only weak AT skew. Third, AT skew is primarily associated with largely non-synonymous first and second codon sites and is seen with respect to their sense direction, not which replicating strand they lie on. The atypical AT skew we show to be a consequence of the strong bias for genes to be co-oriented with the replicating fork, coupled with the selective avoidance of both stop codons and costly amino acids, which tend to have T-rich codons. That intergenic sequence has more A than T, while at mutational equilibrium a preponderance of T is expected, points to a possible further unresolved selective source of skew. When considering a single strand of DNA, it is not necessarily the case that the frequency of each base should equal its complementary partner, such that A = T and G = C. For the leading strand, it is typically the case that Gs are more common than Cs, and Ts more common than As. This bias is widely thought to arise due to different mutational biases during replication. The Firmicutes exhibit an atypical preference for A over T on the leading strand, and here we show that selection, rather than mutation, can explain this exception. For those bases within coding regions, selection acts to inflate the frequency of A over T in order to avoid stop codons and to use metabolically cheap amino acids. Because genes are not orientated randomly, this manifests as an overall enrichment of A on the leading strand. Furthermore, a direct examination of mutational patterns is inconsistent with the observed enrichment of As. Curiously, our data also point to an unresolved source of selection on synonymous and intergenic sites, which are widely assumed to be neutral.
登录
查看更多内容
影响因子：
30.8
作者：
Holt, Kathryn E.;Parkhill, Julian;Mazzoni, Camila J.;Roumagnac, Philippe;Weill, Francois-Xavier;Goodhead, Ian;Rance, Richard;Baker, Stephen;Maskell, Duncan J.;Wain, John;Dolecek, Christiane;Achtman, Mark;Dougan, Gordon
通讯作者：
Dougan, Gordon
影响因子：
3.7
作者：
Barton MD;Delneri D;Oliver SG;Rattray M;Bergman CM
通讯作者：
Bergman CM
影响因子：
4.5
作者：
Hershberg R;Petrov DA
通讯作者：
Petrov DA
影响因子：
4.3
作者：
ANGOV, E;BRUSILOW, WSA
通讯作者：
BRUSILOW, WSA
DOI：
10.1126/science.1182395
发表时间：
2010-01-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harris SR;Feil EJ;Holden MT;Quail MA;Nickerson EK;Chantratita N;Gardete S;Tavares A;Day N;Lindsay JA;Edgeworth JD;de Lencastre H;Parkhill J;Peacock SJ;Bentley SD
通讯作者：
Bentley SD