Oh Brother, Where Art Thou? Finding orthologs in the twilight and midnight zones of sequence similarity
Résumé
Inferring remote orthologs is a persistent challenge in computational biology. The identification of orthologs is necessary for performing evolutionary analyses, comparative genomics, and genome annotation or for functional predictions and sensible planning of experimental studies. If we miss orthologous relationships due to low sequence conservation, we lose a significant amount of information. Given their fast evolutionary rates, remote orthologs can only be identified on protein level. A pair of proteins that has evolved by speciation and has below 30 % sequence identity can be defined as remote orthologs. Their high sequence divergence prevents their unambiguous recognition as orthologous proteins and does not allow a reliable interpretation of their evolutionary relationship. Thus, many remote orthologs remain hidden to date. In this article, I review current methods for remote orthology inference, highlight existing problems in, and discuss potential solutions for discovering remote orthologs.
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