ArticlePLoS computational biology2011
Testing the ortholog conjecture with comparative functional genomic data from mammals.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117 citing papers in PubMed.
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- Comparative transcriptomics reveal the common anteroposterior molecular blueprint of adult bilaterian guts.PLoS biology · 2026Article
- Understanding Functional Evolution in Orthologs and Paralogs.Journal of molecular evolution · 2025Review
- Unveiling the functional fate of duplicated genes through expression profiling and structural analysis.Genome research · 2025Article
- Evaluating sequence and structural similarity metrics for predicting shared paralog functions.NAR genomics and bioinformatics · 2025Article
- Organismal complexity strongly correlates with the number of protein families and domains.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional profiling of the sequence stockpile: a protein pair-based assessment of in silico prediction tools.Bioinformatics (Oxford, England) · 2025Article
- A metric and its derived protein network for evaluation of ortholog database inconsistency.BMC bioinformatics · 2025Article
- Model Organisms in Aging Research: Evolution of Database Annotation and Ortholog Discovery.Genes · 2024Article
- TheInternational journal of molecular sciences · 2024Article
- Decoding functional proteome information in model organisms using protein language models.NAR genomics and bioinformatics · 2024Article
- Computational strategies for cross-species knowledge transfer and translational biomedicine.ArXiv · 2024Article
- A Novel Approach to Comparative RNA-Seq Does Not Support a Conserved Set of Orthologs Underlying Animal Regeneration.Genome biology and evolution · 2024Article
- Integrating phylogenies into single-cell RNA sequencing analysis allows comparisons across species, genes, and cells.PLoS biology · 2024Article
- Petrol Note in Riesling - 1,1,6-Trimethyl-1,2-dihydronaphthalene (TDN) Selectively Activates Human Odorant Receptor OR8H1.Journal of agricultural and food chemistry · 2024Article
- The Theory of Gene Family Histories.Methods in molecular biology (Clifton, N.J.) · 2024Article
57 more citing papers are in PubMed but not listed here.
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
A common assumption in comparative genomics is that orthologous genes share greater functional similarity than do paralogous genes (the "ortholog conjecture"). Many methods used to computationally predict protein function are based on this assumption, even though it is largely untested. Here we present the first large-scale test of the ortholog conjecture using comparative functional genomic data from human and mouse. We use the experimentally derived functions of more than 8,900 genes, as well as an independent microarray dataset, to directly assess our ability to predict function using both orthologs and paralogs. Both datasets show that paralogs are often a much better predictor of function than are orthologs, even at lower sequence identities. Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species. We also find that paralogous pairs residing on the same chromosome are more functionally similar than those on different chromosomes, perhaps due to higher levels of interlocus gene conversion between these pairs. In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence. We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.
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