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专业背景:计算机科学 研究方向与兴趣: JavaEE-Web软件开发, 生物信息学, 数据挖掘与机器学习, 智能信息系统 目前工作: 基因组, 转录组, NGS高通量数据分析, 生物数据挖掘, 植物系统发育和比较进化基因组学

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2倍简并位点及4倍简并位点  

2013-03-25 11:20:22|  分类: 遗传与基因组学 |  标签: |举报 |字号 订阅

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the fourfold degenerate synonymous sites of the third codons (4DTv) value

转自:http://blog.csdn.net/tmjdone/article/details/6945322

4DTV stands for four-fold synonymous (degenerative) third-codon transversion. It represents a transversion in the third nucleotide position within four codons that does not result in a change in corresponding amino acid identity within the protein it codes for. Such an estimate of synonymous mutation rate within a transcribed region of a gene but not in region that experiences selection is a conserved means of estimating divergence within the more recent evolutionary past. Distances corresponding to the 'salicoid' whole-genome duplication events were delineated based on discrete peaks in 4DTV distributions. Duplicated segments were defined as regions on different linkage groups or scaffolds containing six or more homeologous pairs with similar 4DTV values, with fewer than 25 nonhomeologous genes intervening. Gene pairs resulting from the 'salicoid' duplication (apparently common to the Salicaceae) were defined by 4DTV values between 0.04 and 0.17. Microsynteny in flanking regions of segmental duplicates was verified using the Genome Browser. Tandemly duplicated genes that matched the same homeolog were only counted once for this analysis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174922/


Synonymous substitution (Ks) and fourfold degenerate site transversion (4DTV) calculation

For each pair of homologs, we aligned their protein sequences using CLUSTALW (Thompson et al. 1994) and converted the protein alignment to DNA alignment using PAL2NAL (Suyama et al. 2006). Some homologous genes could not produce reliable CLUSTALW alignment for various reasons and were discarded from further analysis. Ks values were calculated using the Nei-Gojobori algorithm (Nei and Gojobori 1986) implemented in the PAML package (Yang 1997). We repeated theKs calculation using other algorithms and found that the differences are small, systematic biases that do not affect major conclusions. We calculated 4DTV values between gene pairs using in-house Perl scripts. 4DTV values are calculated for gene pairs having ≥10 fourfold degenerate sites. Fourfold degenerate sites are codons of amino acid residues G, A, T, P, V, and R, S, L. Raw 4DTV values are then corrected for possible multiple transversions at the same site using this formula:Formula

http://genome.cshlp.org/content/18/12/1944.long  
Unraveling ancient hexaploidy through multiply-aligned angiosperm gene maps

4DTv calculation

4DTv distance (D4DTv) that stands for fourfold synonymous third-codon transversion was calculated to assess the genetic distances between paralogous pairs. In such analysis, the paralogous proteins for each species were pairwise aligned using MAFFT v6.6 [47], and subsequently the corresponding codon-alignment was created according to the resulting protein alignment using a custom PERL script. Based on these alignments, we firstly identified the conserved fourfold degenerate amino acids. And then the corresponding codons were extracted from the codon-alignment and used to calculate the 4DTv distance between each aligning pair. D4DTv ranges from 0 for recently duplicated peptides, to ~0.5 for paralogs with an ancient evolutionary past.

http://www.biomedcentral.com/1471-2229/10/256


在阅读关于同义替换和非同义替换方面的文献时经常遇到这两个名称,2倍简并位点(twofold degenerate site)及4倍简并位点(fourfold degenerate site)。困惑了作者很久,现在将维基百科中的有关解释翻译成为中文以供参考,译文如下:

 

一个遗传密码子通常由三个核苷酸构成,每个核苷酸称为一个位点(position),从左到右依次为第一位点、第二位点、第三位点。

如果密码子的某个位点上任何核苷酸都编码同样的氨基酸,则称这个位点为4倍简并位点。例如甘氨酸密码子(GGA, GGG, GGC, GGU)的第三个位点就是一个4倍简并位点,因为这个位点上所有的核苷酸替换(无论是AGUC)都是同义的,即编码同一个氨基酸。只有某些密码子的第三个位点可能是4倍简并位点。

如果密码子的某个位点上只有四个可能核苷酸其中的两个在该位点时编码同一个氨基酸,那么这个位点就是2倍简并位点。例如谷氨酸密码子GAA, GAG的第三位点就是2倍简并位点,因为密码子GAA, GAG)的第三位点上是AG都编码谷氨酸,而变成其他核苷酸则不再编码谷氨酸。

简并性

大部分密码子具有简并性,即两个或者多个密码子编码同一氨基酸。简并的密码子通常只有第三位碱基不同,例如,GAA和GAG都编码谷氨酰胺。如果不管密码子的第三位为哪种核苷酸,都编码同一种氨基酸,则称之为四重简并(4DTv);如果第三位有四种可能的核苷酸之中的两种,而且编码同一种氨基酸,则称之为二重简并,一般第三位上两种等价的核苷酸同为嘌呤(A/G)或者嘧啶(C/T)。只有两种氨基酸仅由一个密码子编码,一个是甲硫氨酸,由AUG编码,同时也是起始密码子;另一个是色氨酸,由UGG编码。 遗传密码的这些性质可使基因更加耐受点突变。例如,四重简并密码子可以容忍密码子第三位的任何变异;二重简并密码子使三分之一可能的第三位的变异不影响蛋白质序列。由于转换变异(嘌呤变为嘌呤或者嘧啶变为嘧啶)比颠换变异(嘌呤变为嘧啶或者嘧啶变为嘌呤)的可能性更大,因此二重简并密码子也具有很强的对抗突变的能力。不影响氨基酸序列的突变称为沉默突变。

遗传密码


在此我们暂且称AG为等效碱基,及等效碱基之间相互替换不改变所编码的氨基酸。

2倍简并位点上,通常等效碱基要不都是嘌呤,要不都是嘧啶。因此在2倍简并位点上发生颠换(transversion)通常都会导致密码子的非同义突变(所编码的氨基酸发生改变)。

如果一个位点上发生的任何核苷酸改变都导致非同义突变的话,这个位点就是非简并位点。

那么有没有3倍简并位点呢?有且只有一个——异亮氨酸密码子的第三位点,AUU AUCAUA都编码异亮氨酸,而AUA编码甲硫氨酸。在很多计算中,通常把这个3倍简并位点当成2倍简并位点处理。

 

原文:

A position of a codon is said to be a fourfold degenerate site if any nucleotide at this position specifies the same amino acid. For example, the third position of the glycine codons (GGA, GGG, GGC, GGU) is a fourfold degenerate site, because all nucleotide substitutions at this site are synonymous; i.e., they do not change the amino acid. Only the third positions of some codons may be fourfold degenerate.[8]:521–522 A position of a codon is said to be a twofold degenerate site if only two of four possible nucleotides at this position specify the same amino acid. For example, the third position of the glutamic acid codons (GAA, GAG) is a twofold degenerate site. In twofold degenerate sites, the equivalent nucleotides are always either two purines (A/G) or two pyrimidines (C/U), so only transversional substitutions (purine to pyrimidine or pyrimidine to purine) in twofold degenerate sites are nonsynonymous.[8]:521–522 A position of a codon is said to be a non-degenerate site if any mutation at this position results in amino acid substitution. There is only one threefold degenerate site where changing to three of the four nucleotides may have no effect on the amino acid (depending on what it is changed to), while changing to the fourth possible nucleotide always results in an amino acid substitution. This is the third position of an isoleucine codon: AUU, AUC, or AUA all encode isoleucine, but AUG encodes methionine. In computation this position is often treated as a twofold degenerate site.[8]:521–522

 

参考文献

http://en.wikipedia.org/wiki/Genetic_code

 



本文引用地址:http://bbs.sciencenet.cn/blog-508298-427615.html
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