近日，中国科学院北京基因组研究所基因组科学及信息重点实验室通过引入新的参数构造模型，发展了一个新的ka/ks算法，该研究成果在近期出版的Biology Direct杂志上发表。
比较基因组分析是研究生物进化关系的基本工具，非同义替换率(Ka)和同义替换率(Ks)的计算是研究分子进化动力学的重要内容。在过去的二十多年，基于马尔科夫链的核酸替代模型一直在不断发展。于是涌现了诸如NG， LWL， LPB， MLWL， MLPB， YN， MYN等近似算法和GY等极大似然算法。这些方法考虑了三个主要的进化序列动力学特征的部分或者全部：不平衡的转换/颠换率；不平衡的核酸频率；不平衡的转换速率（嘌呤之间的和嘧啶之间的）。
该重点实验室硕博生王大鹏、万昊雷在于军研究员的指导下，在原方法的基础上，通过引入gamma分布来描述序列的不同位点进化速率的不平衡，发展了考虑四种进化特征的新方法gamma-MYN。通过与相关的算法比较，借助于计算机模拟和真实数据集的检验，发现gamma-MYN方法比其他方法在负选择的情况下具有更好的准确度。该研究表明，忽略不同位点的速率的多变性可以导致Ka和Ks值的偏倚，最终导致选择压力评估值(ω)的偏倚。该研究发现对于更加精确的评估选择压力(ω)，以及为其他后续研究提供模型具有重要意义。
目前，该课题组正在通过将新参数嵌入到其他模型中，来研究不同位点多变的突变速率和其他进化参数对ka/ks算法的影响的相互作用。（生物谷Bioon.com）
生物谷推荐原始出处：
Biology Direct 2009, 4:20doi:10.1186/1745-6150-4-20
Gamma-MYN: a new algorithm for estimating Ka and Ks with consideration of variable substitution rates
Da-Peng Wang , Hao-Lei Wan , Song Zhang and Jun Yu
Background
Over the past two decades, there have been several approximate methods that adopt different mutation models and used for estimating nonsynonymous and synonymous substitution rates (Ka and Ks) based on protein-coding sequences across species or even different evolutionary lineages. Among them, MYN method (a Modified version of Yang-Nielsen method) considers three major dynamic features of evolving DNA sequences--bias in transition/transversion rate, nucleotide frequency, and unequal transitional substitution but leaves out another important feature: unequal substitution rates among different sites or nucleotide positions.
Results
We incorporated a new feature for analyzing evolving DNA sequences--unequal substitution rates among different sites--into MYN method, and proposed a modified version, namely gamma-MYN, based on an assumption that the evolutionary rate at each site follows a mode of gamma-distribution. We applied gamma-MYN to analyze the key estimator of selective pressure omega (Ka/Ks) and other relevant parameters in comparison to two other related methods, YN and MYN, and found that neglecting the variation of substitution rates among different sites may lead to biased estimations of omega. Our new method appears to have minimal deviations when relevant parameters vary within normal ranges defined by empirical data.
Conclusions
Our results indicate that unequal substitution rates among different sites have variable influences on omega under different evolutionary rates while both transition/transversion rate ratio and unequal nucleotide frequencies affect Ka and Ks thus selective pressure omega. Reviewers This paper was reviewed by Kateryna Makova, David A. Liberles (nominated by David H Ardell), Zhaolei Zhang (nominated by Mark Gerstein), and Shamil Sunyaev.
