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Homology-based annotation yields 1,042 new candidate genes in the Drosophila melanogaster genome

Nature Genetics volume 27, pages 337–340 (2001)Cite this article

Abstract

The approach to annotating a genome critically affects the number and accuracy of genes identified in the genome sequence. Genome annotation based on stringent gene identification is prone to underestimate the complement of genes encoded in a genome. In contrast, over-prediction of putative genes followed by exhaustive computational sequence, motif and structural homology search will find rarely expressed, possibly unique, new genes at the risk of including non-functional genes. We developed a two-stage approach that combines the merits of stringent genome annotation with the benefits of over-prediction. First we identify plausible genes regardless of matches with EST, cDNA or protein sequences from the organism (stage 1). In the second stage, proteins predicted from the plausible genes are compared at the protein level with EST, cDNA and protein sequences, and protein structures from other organisms (stage 2). Remote but biologically meaningful protein sequence or structure homologies provide supporting evidence for genuine genes. The method, applied to the Drosophila melanogaster genome, validated 1,042 novel candidate genes after filtering 19,410 plausible genes, of which 12,124 matched the original 13,601 annotated genes1. This annotation strategy is applicable to genomes of all organisms, including human.

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Acknowledgements

We thank S. Burley, M. Vidal, J. Sorge, J. Goncalves, M. Ashburner, S. Lewis, M. Young and U. Gaul for insights and comments. This work was partially supported by the Mathers, Sinsheimer and Mallinkrodt Foundations, National Cancer Institute Health grant R33CA84699, National Institutes of Health grant P50GM62529, and the National Science Foundation grant DBI-9984882.

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Author notes

  1. Shuba Gopal and Mark Schroeder: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratories of Computational Genomics, The Rockefeller University, New York, New York, USA

    Shuba Gopal, Mark Schroeder, Ursula Pieper, Alexander Sczyrba, Gulriz Aytekin-Kurban, Stefan Bekiranov, J. Eduardo Fajardo & Terry Gaasterland

  2. Biophysics, The Rockefeller University, New York, New York, USA

    Ursula Pieper, Narayanan Eswar, Roberto Sanchez & Andrej Sali

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  1. Shuba Gopal
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Correspondence to Terry Gaasterland.

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Gopal, S., Schroeder, M., Pieper, U. et al. Homology-based annotation yields 1,042 new candidate genes in the Drosophila melanogaster genome. Nat Genet 27, 337–340 (2001). https://doi.org/10.1038/85922

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