近日，中國科學(xué)院北京基因組研究所基因組科學(xué)及信息重點實驗室通過引入新的參數(shù)構(gòu)造模型,，發(fā)展了一個新的ka/ks算法，該研究成果在近期出版的Biology Direct雜志上發(fā)表,。
比較基因組分析是研究生物進(jìn)化關(guān)系的基本工具,，非同義替換率(Ka)和同義替換率(Ks)的計算是研究分子進(jìn)化動力學(xué)的重要內(nèi)容。在過去的二十多年,，基于馬爾科夫鏈的核酸替代模型一直在不斷發(fā)展,。于是涌現(xiàn)了諸如NG， LWL,， LPB,， MLWL， MLPB,， YN,， MYN等近似算法和GY等極大似然算法。這些方法考慮了三個主要的進(jìn)化序列動力學(xué)特征的部分或者全部：不平衡的轉(zhuǎn)換/顛換率,；不平衡的核酸頻率,；不平衡的轉(zhuǎn)換速率（嘌呤之間的和嘧啶之間的）。
該重點實驗室碩博生王大鵬,、萬昊雷在于軍研究員的指導(dǎo)下,，在原方法的基礎(chǔ)上，通過引入gamma分布來描述序列的不同位點進(jìn)化速率的不平衡，發(fā)展了考慮四種進(jìn)化特征的新方法gamma-MYN,。通過與相關(guān)的算法比較,，借助于計算機模擬和真實數(shù)據(jù)集的檢驗,，發(fā)現(xiàn)gamma-MYN方法比其他方法在負(fù)選擇的情況下具有更好的準(zhǔn)確度,。該研究表明，忽略不同位點的速率的多變性可以導(dǎo)致Ka和Ks值的偏倚,，最終導(dǎo)致選擇壓力評估值(ω)的偏倚,。該研究發(fā)現(xiàn)對于更加精確的評估選擇壓力(ω)，以及為其他后續(xù)研究提供模型具有重要意義,。
目前,，該課題組正在通過將新參數(shù)嵌入到其他模型中，來研究不同位點多變的突變速率和其他進(jìn)化參數(shù)對ka/ks算法的影響的相互作用,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
