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Correlation between sequence conservation and the genomic context after gene duplication.

Richard A Notebaart1, Martijn A Huynen, Bas Teusink

  • 1Center for Molecular and Biomolecular Informatics, Radboud University, Nijmegen, The Netherlands.

Nucleic Acids Research
|November 1, 2005
PubMed
Summary
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Gene duplication complicates gene function prediction. Combining sequence similarity with gene neighborhood or co-expression data improves identifying functional orthologs, especially with inparalogs.

Area of Science:

  • Comparative genomics
  • Bioinformatics
  • Evolutionary biology

Background:

  • Gene duplication is a major challenge in predicting gene function accurately.
  • Inparalogs, genes duplicated after speciation, complicate ortholog identification.

Purpose of the Study:

  • To investigate the relationship between sequence similarity and ancestral gene neighborhood conservation for inparalogs.
  • To assess the impact of gene duplication on reliable gene function prediction.

Main Methods:

  • Comparative genomic analysis of orthologs across genome pairs.
  • Analysis of inparalogs, focusing on sequence similarity and gene neighborhood conservation.
  • Investigating the evolutionary rates of inparalogs relative to their orthologs.

Related Experiment Videos

Main Results:

  • A significant fraction (29-38%) of inparalogs showed inconsistency between sequence similarity and gene neighborhood conservation.
  • This inconsistency is attributed to similar evolutionary rates of inparalogs, not lack of divergence time.
  • Gene duplication significantly impacts the reliability of gene function prediction based solely on sequence similarity.

Conclusions:

  • Relying solely on sequence similarity for ortholog identification in the presence of inparalogs can be misleading.
  • Combining sequence information with contextual data (gene neighborhood in prokaryotes, co-expression in eukaryotes) is crucial for accurate functional ortholog prediction.
  • Improved methods are needed to handle gene duplication in comparative genomics for robust gene function prediction.