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Correlation Between Ka/Ks and Ks is Related to Substitution Model and Evolutionary Lineage

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Abstract

In 2005, Wyckoff and coworkers described a surprisingly strong correlation between Ka/Ks and Ks in several data sets using the LPB93 algorithm. This finding indicated the possibility of a paradigm shift in the way selection strength can be measured using the Ka/Ks ratio. We carried out a calculation of Ka and Ks using six different algorithms on three cross-species orthologous data sets and found a highly variable correlation among the algorithms and lineages. Algorithms based on the GY-HKY substitution model exhibit a weaker positive correlation or a stronger negative correlation than those based on the K2P and JC69 substitution model. Even if one algorithm shows a positive correlation between Ka/Ks and Ks in a warm-blooded lineage, it may show no correlation in a cold-blooded lineage. This algorithm-related and evolutionary lineage-related correlation indicates the need for great caution in drawing conclusions when using only one Ka and Ks algorithm in a genomewide analysis of selection strength. Our results indicated that currently used algorithms for Ka and Ks calculations are flawed and need improvements.

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Acknowledgments

We thank Laurie Goodman for her extensive editing of our manuscript. We thank Lin Fang, Jia Ye, and Hongkun Zheng for their constructive comments on this work. This project was supported by the Chinese Academy of Sciences (KSCX2-YW-N–023, GJHZ0701-6), the Ministry of Science and Technology under high-tech program 863 (2006AA02Z334, 2006AA10A121), the National Natural Science Foundation of China (90608010, 90403130, 30221004, 90612019, 30392130), and the Beijing Municipal Science and Technology Commission (D07030200740000). The project was also supported by Ole Rømer grants from the Danish Natural Science Research Council and the Danish Medical Research Council. J.L. collected the data and carried out all analyses. J.L., Z.Z., and S.V. wrote the manuscript. J.Y., G.K.W., and J.W. designed and coordinated the study. All authors read and approved the final manuscript.

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Correspondence to Gane Ka-Shu Wong or Jun Wang.

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Jun Li, Zhang Zhang and Søren Vang contributed equally to this work.

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Li, J., Zhang, Z., Vang, S. et al. Correlation Between Ka/Ks and Ks is Related to Substitution Model and Evolutionary Lineage. J Mol Evol 68, 414–423 (2009). https://doi.org/10.1007/s00239-009-9222-9

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  • DOI: https://doi.org/10.1007/s00239-009-9222-9

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