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      Accuracy and Power of Statistical Methods for Detecting Adaptive Evolution in Protein Coding Sequences and for Identifying Positively Selected Sites

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      Genetics

      Genetics Society of America

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          Abstract

          The parsimony method of Suzuki and Gojobori (1999) and the maximum likelihood method developed from the work of Nielsen and Yang (1998) are two widely used methods for detecting positive selection in homologous protein coding sequences. Both methods consider an excess of nonsynonymous (replacement) substitutions as evidence for positive selection. Previously published simulation studies comparing the performance of the two methods show contradictory results. Here we conduct a more thorough simulation study to cover and extend the parameter space used in previous studies. We also reanalyzed an HLA data set that was previously proposed to cause problems when analyzed using the maximum likelihood method. Our new simulations and a reanalysis of the HLA data demonstrate that the maximum likelihood method has good power and accuracy in detecting positive selection over a wide range of parameter values. Previous studies reporting poor performance of the method appear to be due to numerical problems in the optimization algorithms and did not reflect the true performance of the method. The parsimony method has a very low rate of false positives but very little power for detecting positive selection or identifying positively selected sites.

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          Most cited references 26

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          Toward Defining the Course of Evolution: Minimum Change for a Specific Tree Topology

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            Statistical methods for detecting molecular adaptation.

            The past few years have seen the development of powerful statistical methods for detecting adaptive molecular evolution. These methods compare synonymous and nonsynonymous substitution rates in protein-coding genes, and regard a nonsynonymous rate elevated above the synonymous rate as evidence for darwinian selection. Numerous cases of molecular adaptation are being identified in various systems from viruses to humans. Although previous analyses averaging rates over sites and time have little power, recent methods designed to detect positive selection at individual sites and lineages have been successful. Here, we summarize recent statistical methods for detecting molecular adaptation, and discuss their limitations and possible improvements.
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              The rapid evolution of reproductive proteins.

              Many genes that mediate sexual reproduction, such as those involved in gamete recognition, diverge rapidly, often as a result of adaptive evolution. This widespread phenomenon might have important consequences, such as the establishment of barriers to fertilization that might lead to speciation. Sequence comparisons and functional studies are beginning to show the extent to which the rapid divergence of reproductive proteins is involved in the speciation process.
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                Author and article information

                Journal
                Genetics
                Genetics
                Genetics Society of America
                0016-6731
                1943-2631
                October 28 2004
                October 2004
                October 2004
                October 28 2004
                : 168
                : 2
                : 1041-1051
                Article
                10.1534/genetics.104.031153
                1448811
                15514074
                © 2004

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