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PLOS Computational Biology 2012

The Ortholog Conjecture Is Untestable by the Current Gene Ontology but Is Supported by RNA Sequencing Data

DOI: 10.1371/journal.pcbi.1002784

Xiaoshu Chen,Jianzhi Zhang

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Abstract:

The ortholog conjecture posits that orthologous genes are functionally more similar than paralogous genes. This conjecture is a cornerstone of phylogenomics and is used daily by both computational and experimental biologists in predicting, interpreting, and understanding gene functions. A recent study, however, challenged the ortholog conjecture on the basis of experimentally derived Gene Ontology (GO) annotations and microarray gene expression data in human and mouse. It instead proposed that the functional similarity of homologous genes is primarily determined by the cellular context in which the genes act, explaining why a greater functional similarity of (within-species) paralogs than (between-species) orthologs was observed. Here we show that GO-based functional similarity between human and mouse orthologs, relative to that between paralogs, has been increasing in the last five years. Further, compared with paralogs, orthologs are less likely to be included in the same study, causing an underestimation in their functional similarity. A close examination of functional studies of homologs with identical protein sequences reveals experimental biases, annotation errors, and homology-based functional inferences that are labeled in GO as experimental. These problems and the temporary nature of the GO-based finding make the current GO inappropriate for testing the ortholog conjecture. RNA sequencing (RNA-Seq) is known to be superior to microarray for comparing the expressions of different genes or in different species. Our analysis of a large RNA-Seq dataset of multiple tissues from eight mammals and the chicken shows that the expression similarity between orthologs is significantly higher than that between within-species paralogs, supporting the ortholog conjecture and refuting the cellular context hypothesis for gene expression. We conclude that the ortholog conjecture remains largely valid to the extent that it has been tested, but further scrutiny using more and better functional data is needed.

References

[1]	Fitch W (1970) Distinguishing homologous from analogous proteins. Syst Zool 19: 99–106. doi: 10.2307/2412448
[2]	Sonnhammer EL, Koonin EV (2002) Orthology, paralogy and proposed classification for paralog subtypes. Trends Genet 18: 619–620. doi: 10.1016/s0168-9525(02)02793-2
[3]	Koonin EV (2005) Orthologs, paralogs, and evolutionary genomics. Annu Rev Genet 39: 309–338. doi: 10.1146/annurev.genet.39.073003.114725
[4]	Nehrt NL, Clark WT, Radivojac P, Hahn MW (2011) Testing the ortholog conjecture with comparative functional genomic data from mammals. PLoS Comput Biol 7: e1002073. doi: 10.1371/journal.pcbi.1002073
[5]	Engelhardt BE, Jordan MI, Muratore KE, Brenner SE (2005) Protein molecular function prediction by Bayesian phylogenomics. PLoS Comput Biol 1: e45. doi: 10.1371/journal.pcbi.0010045
[6]	Tatusov RL, Koonin EV, Lipman DJ (1997) A genomic perspective on protein families. Science 278: 631–637. doi: 10.1126/science.278.5338.631
[7]	Dolinski K, Botstein D (2007) Orthology and functional conservation in eukaryotes. Annu Rev Genet 41: 465–507. doi: 10.1146/annurev.genet.40.110405.090439
[8]	Eisen JA (1998) Phylogenomics: improving functional predictions for uncharacterized genes by evolutionary analysis. Genome Res 8: 163–167. doi: 10.1101/gr.8.3.163
[9]	Yu H, Luscombe NM, Lu HX, Zhu X, Xia Y, et al. (2004) Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs. Genome Res 14: 1107–1118. doi: 10.1101/gr.1774904
[10]	Qian W, He X, Chan E, Xu H, Zhang J (2011) Measuring the evolutionary rate of protein-protein interaction. Proc Natl Acad Sci U S A 108: 8725–8730. doi: 10.1073/pnas.1104695108
[11]	McGary KL, Park TJ, Woods JO, Cha HJ, Wallingford JB, et al. (2010) Systematic discovery of nonobvious human disease models through orthologous phenotypes. Proc Natl Acad Sci U S A 107: 6544–6549. doi: 10.1073/pnas.0910200107
[12]	Zhang J, He X (2005) Significant impact of protein dispensability on the instantaneous rate of protein evolution. Mol Biol Evol 22: 1147–1155. doi: 10.1093/molbev/msi101
[13]	Liao BY, Zhang J (2008) Null mutations in human and mouse orthologs frequently result in different phenotypes. Proc Natl Acad Sci U S A 105: 6987–6992. doi: 10.1073/pnas.0800387105
[14]	Kim DU, Hayles J, Kim D, Wood V, Park HO, et al. (2010) Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe. Nat Biotechnol 28: 617–623. doi: 10.1038/nbt.1628
[15]	Ohno S (1970) Evolution by Gene Duplication. Berlin: Springer-Verlag.
[16]	Force A, Lynch M, Pickett FB, Amores A, Yan YL, et al. (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151: 1531–1545.
[17]	Zhang J (2003) Evolution by gene duplication: an update. Trends Eco Evol 18: 292–298. doi: 10.1016/s0169-5347(03)00033-8
[18]	Qian W, Liao BY, Chang AY, Zhang J (2010) Maintenance of duplicate genes and their functional redundancy by reduced expression. Trends Genet 26: 425–430. doi: 10.1016/j.tig.2010.07.002
[19]	Studer RA, Robinson-Rechavi M (2009) How confident can we be that orthologs are similar, but paralogs differ? Trends Genet 25: 210–216. doi: 10.1016/j.tig.2009.03.004
[20]	Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, et al. (2000) Gene ontology: tool for the unification of biology. Nat Genet 25: 25–29. doi: 10.1038/75556
[21]	Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, et al. (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci U S A 101: 6062–6067. doi: 10.1073/pnas.0400782101
[22]	Rogers MF, Ben-Hur A (2009) The use of gene ontology evidence codes in preventing classifier assessment bias. Bioinformatics 25: 1173–1177. doi: 10.1093/bioinformatics/btp122
[23]	Thomas PD, Wood V, Mungall CJ, Lewis SE, Blake JA (2012) On the use of gene ontology annotations to assess functional similarity among orthologs and paralogs: A short report. PLoS Comput Biol 8: e1002386. doi: 10.1371/journal.pcbi.1002386
[24]	Xiong Y, Chen X, Chen Z, Wang X, Shi S, et al. (2010) RNA sequencing shows no dosage compensation of the active X-chromosome. Nat Genet 42: 1043–1047. doi: 10.1038/ng.711
[25]	Liao BY, Zhang J (2006) Evolutionary conservation of expression profiles between human and mouse orthologous genes. Mol Biol Evol 23: 530–540. doi: 10.1093/molbev/msj054
[26]	Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10: 57–63. doi: 10.1038/nrg2484
[27]	Fu X, Fu N, Guo S, Yan Z, Xu Y, et al. (2009) Estimating accuracy of RNA-Seq and microarrays with proteomics. BMC Genomics 10: 161. doi: 10.1186/1471-2164-10-161
[28]	Marioni JC, Mason CE, Mane SM, Stephens M, Gilad Y (2008) RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res 18: 1509–1517. doi: 10.1101/gr.079558.108
[29]	The Gene Ontology Consortium (2012) The Gene Ontology: enhancements for 2011. Nucleic Acids Res 40: D559–564. doi: 10.1093/nar/gkr1028
[30]	Clogg C, Petkova E, Haritou A (1995) Statistical methods for comparing regression coefficients between models. Am J Sociol 100: 1261–1293. doi: 10.1086/230638
[31]	Paternoster R, Brame R, Mazerolle P, Piquero A (1998) Using the correct statistical test for the equality of regression coefficients. Criminology 36: 859–866. doi: 10.1111/j.1745-9125.1998.tb01268.x
[32]	Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, et al. (2000) Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation. Brain Res Mol Brain Res 85: 1–12. doi: 10.1016/s0169-328x(00)00218-7
[33]	Ohkawara B, Shirakabe K, Hyodo-Miura J, Matsuo R, Ueno N, et al. (2004) Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm induction. Genes Dev 18: 381–386. doi: 10.1101/gad.1166904
[34]	Phng LK, Potente M, Leslie JD, Babbage J, Nyqvist D, et al. (2009) Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. Dev Cell 16: 70–82. doi: 10.1016/j.devcel.2008.12.009
[35]	Orioli D, Colaluca IN, Stefanini M, Riva S, Dotti CG, et al. (2006) Rac3-induced neuritogenesis requires binding to Neurabin I. Mol Biol Cell 17: 2391–2400. doi: 10.1091/mbc.e05-08-0753
[36]	Shekhar MP, Gerard B, Pauley RJ, Williams BO, Tait L (2008) Rad6B is a positive regulator of beta-catenin stabilization. Cancer Res 68: 1741–1750. doi: 10.1158/0008-5472.can-07-2111
[37]	Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, et al. (2001) CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107: 27–41. doi: 10.1016/s0092-8674(01)00520-7
[38]	Lopez-Fernandez LA, Parraga M, del Mazo J (2002) Ilf2 is regulated during meiosis and associated to transcriptionally active chromatin. Mech Dev 111: 153–157. doi: 10.1016/s0925-4773(01)00612-8
[39]	Coates PJ, Nenutil R, McGregor A, Picksley SM, Crouch DH, et al. (2001) Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. Exp Cell Res 265: 262–273. doi: 10.1006/excr.2001.5166
[40]	Yu H, Gao L, Tu K, Guo Z (2005) Broadly predicting specific gene functions with expression similarity and taxonomy similarity. Gene 352: 75–81. doi: 10.1016/j.gene.2005.03.033
[41]	Yanai I, Graur D, Ophir R (2004) Incongruent expression profiles between human and mouse orthologous genes suggest widespread neutral evolution of transcription control. OMICS 8: 15–24. doi: 10.1089/153623104773547462
[42]	Brawand D, Soumillon M, Necsulea A, Julien P, Csardi G, et al. (2011) The evolution of gene expression levels in mammalian organs. Nature 478: 343–348. doi: 10.1038/nature10532
[43]	Zhang J (2011) A panorama of mammalian gene expression evolution. Mol Syst Biol 7: 552. doi: 10.1038/msb.2011.86
[44]	Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5: 621–628. doi: 10.1038/nmeth.1226
[45]	Piasecka B, Robinson-Rechavi M, Bergmann S (2012) Correcting for the bias due to expression specificity improves the estimation of constrained evolution of expression between mouse and human. Bioinformatics 28: 1865–1872. doi: 10.1093/bioinformatics/bts266
[46]	Pereira V, Waxman D, Eyre-Walker A (2009) A problem with the correlation coefficient as a measure of gene expression divergence. Genetics 183: 1597–1600. doi: 10.1534/genetics.109.110247
[47]	Khaitovich P, Hellmann I, Enard W, Nowick K, Leinweber M, et al. (2005) Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309: 1850–1854. doi: 10.1126/science.1108296
[48]	Pal C, Papp B, Hurst LD (2001) Highly expressed genes in yeast evolve slowly. Genetics 158: 927–931.
[49]	Drummond DA, Wilke CO (2008) Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution. Cell 134: 341–352. doi: 10.1016/j.cell.2008.05.042
[50]	Yang JR, Zhuang SM, Zhang J (2010) Impact of translational error-induced and error-free misfolding on the rate of protein evolution. Mol Syst Biol 6: 421. doi: 10.1038/msb.2010.78
[51]	Yang JR, Liao BY, Zhuang SM, Zhang J (2012) Protein misinteraction avoidance causes highly expressed proteins to evolve slowly. Proc Natl Acad Sci U S A 109: E831–840. doi: 10.1073/pnas.1117408109
[52]	Altenhoff AM, Studer RA, Robinson-Rechavi M, Dessimoz C (2012) Resolving the ortholog conjecture: Orthologs tend to be weakly, but significantly, more similar in function than paralogs. PLoS Comput Biol 8: e1002514. doi: 10.1371/journal.pcbi.1002514
[53]	Huerta-Cepas J, Dopazo J, Huynen MA, Gabaldon T (2011) Evidence for short-time divergence and long-time conservation of tissue-specific expression after gene duplication. Brief Bioinform 12: 442–448. doi: 10.1093/bib/bbr022
[54]	Gharib WH, Robinson-Rechavi M (2011) When orthologs diverge between human and mouse. Brief Bioinform 12: 436–441. doi: 10.1093/bib/bbr031
[55]	Qian W, Zhang J (2009) Protein subcellular relocalization in the evolution of yeast singleton and duplicate genes. Genome Biol Evol 1: 198–204. doi: 10.1093/gbe/evp021
[56]	Mika S, Rost B (2006) Protein-protein interactions more conserved within species than across species. PLoS Comput Biol 2: e79. doi: 10.1371/journal.pcbi.0020079
[57]	Flicek P, Amode MR, Barrell D, Beal K, Brent S, et al. (2011) Ensembl 2011. Nucleic Acids Res 39: D800–806. doi: 10.1093/nar/gkq1064
[58]	Barrell D, Dimmer E, Huntley RP, Binns D, O'Donovan C, et al. (2009) The GOA database in 2009–an integrated Gene Ontology Annotation resource. Nucleic Acids Res 37: D396–403. doi: 10.1093/nar/gkn803
[59]	Pesquita C, Faria D, Falcao AO, Lord P, Couto FM (2009) Semantic similarity in biomedical ontologies. PLoS Comput Biol 5: e1000443. doi: 10.1371/journal.pcbi.1000443

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