A chemical-distance-based test for positive Darwinian selection

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There are very few instances in which positive Darwinian selection has been convincingly demonstrated at the molecular level. In this study, we present a novel test for detecting positive selection at the amino-acid level. In this test, amino-acid replacements are characterized in terms of chemical distances, i.e., degrees of dissimilarity between the exchanged residues in a protein. The test identifies statistically significant deviations of the mean observed chemical distance from its expectation, either along a phylogenetic lineage or across a subtree. The mean observed distance is calculated as the average chemical distance over all possible ancestral sequence reconstructions, weighted by their likelihood. Our method substantially improves over previous approaches by taking into account the stochastic process, tree phylogeny, among site rate variation, and alternative ancestral reconstructions. We provide a linear time algorithm for applying this test to all branches and all subtrees of a given phylogenetic tree. We validate this approach by applying it to two well-studied datasets, the MHC class I glycoproteins serving as a positive control, and the house-keeping gene carbonic anhydrase I serving as a negative control.

Original languageEnglish
Title of host publicationAlgorithms in Bioinformatics - First International Workshop, WABI 2001 Århus Denmark, August 28-31, 2001 Proceedings
EditorsBernard M. E. Moret, Olivier Gascuel
PublisherSpringer Verlag
Number of pages14
ISBN (Print)3540425160
StatePublished - 2001
Event1st International Workshop on Algorithms in Bioinformatics, WABI 2001 - Arhus, Denmark
Duration: 28 Aug 200131 Aug 2001

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349


Conference1st International Workshop on Algorithms in Bioinformatics, WABI 2001


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