Journal Article

A Tight Link between Orthologs and Bidirectional Best Hits in Bacterial and Archaeal Genomes

Yuri I. Wolf and Eugene V. Koonin

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 4, issue 12, pages 1286-1294
Published in print January 2012 |
Published online November 2012 | e-ISSN: 1759-6653 | DOI: http://dx.doi.org/10.1093/gbe/evs100

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Orthologous relationships between genes are routinely inferred from bidirectional best hits (BBH) in pairwise genome comparisons. However, to our knowledge, it has never been quantitatively demonstrated that orthologs form BBH. To test this “BBH-orthology conjecture,” we take advantage of the operon organization of bacterial and archaeal genomes and assume that, when two genes in compared genomes are flanked by two BBH show statistically significant sequence similarity to one another, these genes are bona fide orthologs. Under this assumption, we tested whether middle genes in “syntenic orthologous gene triplets” form BBH. We found that this was the case in more than 95% of the syntenic gene triplets in all genome comparisons. A detailed examination of the exceptions to this pattern, including maximum likelihood phylogenetic tree analysis, showed that some of these deviations involved artifacts of genome annotation, whereas very small fractions represented random assignment of the best hit to one of closely related in-paralogs, paralogous displacement in situ, or even less frequent genuine violations of the BBH–orthology conjecture caused by acceleration of evolution in one of the orthologs. We conclude that, at least in prokaryotes, genes for which independent evidence of orthology is available typically form BBH and, conversely, BBH can serve as a strong indication of gene orthology.

Keywords: orthology; bidirectional best hit; genome comparison; synteny

Journal Article.  3066 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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