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Cited by 643Genomics and Phylogenetic StudiesChromosomal and Genetic VariationsBioinformatics and Genomic Networks

Functional and evolutionary implications of gene orthology

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Gabaldón, Toni, Koonin, Eugene V.·2013·Nature Reviews Genetics
DOI 10.1038/nrg3456PMC PMC5877793
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Abstract

Orthologues and paralogues are types of homologous genes that are related by speciation or duplication, respectively. Orthologous genes are generally assumed to retain equivalent functions in different organisms and to share other key properties. Several recent comparative genomic studies have focused on testing these expectations. Here we discuss the complexity of the evolution of gene-phenotype relationships and assess the validity of the key implications of orthology and paralogy relationships as general statistical trends and guiding principles.

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  • Distinguishing orthologs and paralogs is a fundamental problem in evolutionary and molecular biology and a prerequisite for many genomic analyses.

    “Distinguishing orthologs and paralogs is a fundamental problem in evolutionary and molecular biology (1) and a prerequisite for many genomic analyses, including reconstructing phylogenetic trees, predicting gene function, investigating molecular and genome evolution, and discovering differences in genes that underlie phenotypes of the sequenced species (2–6).”

    From Integrating gene annotation with orthology inference at scale (2023) · cites this paper as [1]

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  1. [1]Fitch WM Distinguishing homologous from analogous proteins Systemat Zool 19 99 106 1970 5449325
  2. [2]Fitch WM Homology a personal view on some of the problems Trends Genet 16 227 231 2000 10782117
  3. [3]Koonin EV Walter Fitch and the orthology paradigm Brief Bioinform 12 377 378 2011 21949265 PMC3178060
  4. [4]Baldauf SL Phylogeny for the faint of heart: a tutorial Trends Genet 19 345 351 2003 12801728
  5. [5]Sonnhammer EL Koonin EV Orthology, paralogy and proposed classification for paralog subtypes Trends Genet 18 619 620 2002 12446146
  6. [6]Koonin EV Orthologs, paralogs and evolutionary genomics Annu Rev Genet 39 309 338 2005 16285863
  7. [7]Dolinski K Botstein D Orthology and functional conservation in eukaryotes Annu Rev Genet 41 465 507 2007 17678444
  8. [8]Studer RA Robinson-Rechavi M How confident can we be that orthologs are similar, but paralogs differ? Trends Genet 25 210 216 2009 19368988
  9. [9]Nehrt NL Clark WT Radivojac P Hahn MW Testing the ortholog conjecture with comparative functional genomic data from mammals PLoS Comput Biol 7 e1002073 2011 21695233 PMC3111532
  10. [10]Kuzniar A van Ham RC Pongor S Leunissen JA The quest for orthologs: finding the corresponding gene across genomes Trends Genet 24 539 551 2008 18819722
  11. [11]Gabaldón T Large-scale assignment of orthology: back to phylogenetics? Genome Biol 9 235 2008 18983710 PMC2760865
  12. [12]Altenhoff AM Dessimoz C Phylogenetic and functional assessment of orthologs inference projects and methods PLoS Comput Biol 5 e1000262 2009 19148271 PMC2612752
  13. [13]Trachana K Orthology prediction methods: a quality assessment using curated protein families Bioessays 33 769 780 2011 21853451 PMC3193375
  14. [14]Kristensen DM Wolf YI Mushegian AR Koonin EV Computational methods for Gene Orthology inference Brief Bioinform 12 379 391 2011 21690100 PMC3178053
  15. [15]Gabaldón T Joining forces in the quest for orthologs Genome Biol 10 403 2009 19785718 PMC2768974
  16. [16]Dessimoz C Gabaldón T Roos DS Sonnhammer EL Herrero J Toward community standards in the quest for orthologs Bioinformatics 28 900 904 2012 22332236 PMC3307119
  17. [17]Descorps-Declere S Lemoine F Sculo Q Lespinet O Labedan B The multiple facets of homology and their use in comparative genomics to study the evolution of genes, genomes, and species Biochimie 90 595 608 2008 17961904
  18. [18]Mahmood K Webb GI Song J Whisstock JC Konagurthu AS Efficient large-scale protein sequence comparison and gene matching to identify orthologs and co-orthologs Nucleic Acids Res 40 e44 2012 22210858 PMC3315314
  19. [19]Roux J Robinson-Rechavi M An ontology to clarify homology-related concepts Trends Genet 26 99 102 2010 20116127
  20. [20]Tatusov RL Koonin EV Lipman DJ A genomic perspective on protein families Science 278 631 637 1997 9381173
  21. [21]Remm M Storm CE Sonnhammer EL Automatic clustering of orthologs and in-paralogs from pairwise species comparisons J Mol Biol 314 1041 1052 2001 11743721
  22. [22]Koonin EV Aravind L Kondrashov AS The impact of comparative genomics on our understanding of evolution Cell 101 573 576 2000 10892642
  23. [23]Sjolander K Datta RS Shen Y Shoffner GM Ortholog identification in the presence of domain architecture rearrangement Brief Bioinform 12 413 422 2011 21712343 PMC3178056
  24. [24]Forslund K Sonnhammer EL Evolution of protein domain architectures Methods Mol Biol 856 187 216 2012 22399460
  25. [25]Hartmann B Valcarcel J Decrypting the genome’s alternative messages Curr Opin Cell Biol 21 377 386 2009 19307111
  26. [26]Irimia M Blencowe BJ Alternative splicing: decoding an expansive regulatory layer Curr Opin Cell Biol 24 323 332 2012 22465326
  27. [27]Basu MK Poliakov E Rogozin IB Domain mobility in proteins: functional and evolutionary implications Brief Bioinform 10 205 216 2009 19151098 PMC2722818
  28. [28]Ouzounis C Orthology: another terminology muddle Trends Genet 15 445 1999 10529805
  29. [29]Theissen G Birth, life and death of developmental control genes: new challenges for the homology concept Theory Biosci 124 199 212 2005 17046356
  30. [30]Bandyopadhyay S Sharan R Ideker T Systematic identification of functional orthologs based on protein network comparison Genome Res 16 428 435 2006 16510899 PMC1415213
  31. [31]Singh R Xu J Berger B Global alignment of multiple protein interaction networks with application to functional orthology detection Proc Natl Acad Sci USA 105 12763 12768 2008 18725631 PMC2522262
  32. [32]Huynen MA Bork P Measuring genome evolution Proc Natl Acad Sci USA 95 5849 5856 1998 9600883 PMC34486
  33. [34]Kumar S Molecular clocks: four decades of evolution Nature Rev Genet 6 654 662 2005 16136655
  34. [35]Koski LB Golding GB The closest BLAST hit is often not the nearest neighbor J Mol Evol 52 540 542 2001 11443357
  35. [36]Hulsen T Huynen MA de Vlieg J Groenen PM Benchmarking ortholog identification methods using functional genomics data Genome Biol 7 R31 2006 16613613 PMC1557999
  36. [37]Wolf YI Koonin EV A tight link between orthologs and bidirectional best hits in bacterial and archaeal genomes Genome Biol Evol 1286 1294 2012 23160176 PMC3542571
  37. [38]Koonin EV Comparative genomics, minimal gene-sets and the last universal common ancestor Nature Rev Microbiol 1 127 136 2003 15035042
  38. [39]Snel B Huynen MA Dutilh BE Genome trees and the nature of genome evolution Annu Rev Microbiol 59 191 209 2005 16153168
  39. [40]Blomme T The gain and loss of genes during 600 million years of vertebrate evolution Genome Biol 7 R43 2006 16723033 PMC1779523
  40. [41]Makarova KS Wolf YI Mekhedov SL Mirkin BG Koonin EV Ancestral paralogs and pseudoparalogs and their role in the emergence of the eukaryotic cell Nucleic Acids Res 33 4626 4638 2005 16106042 PMC1187821
  41. [42]Huerta-Cepas J Gabaldón T Assigning duplication events to relative temporal scales in genome-wide studies Bioinformatics 27 38 45 2011 21075746
  42. [43]Forslund K Pekkari I Sonnhammer EL Domain architecture conservation in orthologs BMC Bioinformatics 12 326 2011 21819573 PMC3215765
  43. [44]Koonin EV A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes Genome Biol 5 R7 2004 14759257 PMC395751
  44. [45]Peterson ME Evolutionary constraints on structural similarity in orthologs and paralogs Protein Sci 18 1306 1315 2009 19472362 PMC2774440
  45. [46]Mushegian AR Koonin EV A minimal gene set for cellular life derived by comparison of complete bacterial genomes Proc Natl Acad Sci USA 93 10268 10273 1996 8816789 PMC38373
  46. [47]Galperin MY Walker DR Koonin EV Analogous enzymes: independent inventions in enzyme evolution Genome Res 8 779 790 1998 9724324
  47. [48]Omelchenko MV Galperin MY Wolf YI Koonin EV Non-homologous isofunctional enzymes: a systematic analysis of alternative solutions in enzyme evolution Biol Direct 5 31 2010 20433725 PMC2876114
  48. [49]Lynch VJ Wagner GP Resurrecting the role of transcription factor change in developmental evolution Evolution 62 2131 2154 2008 18564379
  49. [50]Casci T Functional genomics: Degrees of similarity Nature Rev Genet 12 522 2011 21765456
  50. [51]Thomas PD Wood V Mungall CJ Lewis SE Blake JA On the use of gene ontology annotations to assess functional similarity among orthologs and paralogs: a short report PLoS Comput Biol 8 e1002386 2012 22359495 PMC3280971
  51. [52]Altenhoff AM Studer RA Robinson-Rechavi M Dessimoz C Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs PLoS Comput Biol 8 e1002514 2012 22615551 PMC3355068
  52. [53]Huerta-Cepas J Dopazo J Huynen MA Gabaldón T Evidence for short-time divergence and long-time conservation of tissue-specific expression after gene duplication Brief Bioinform 12 442 448 2011 21515902
  53. [54]Chen X Zhang J The ortholog conjecture is untestable by the current gene ontology but is supported by RNA sequencing data PLoS Comput Biol 8 e1002784 2012 23209392 PMC3510086
  54. [55]Mohd-Padil H Mohd-Adnan A Gabaldón T Phylogenetic analyses uncover a novel clade of transferring in non-mammalian vertebrates Mol Biol Evol 30 894 905 2013 23258311 PMC3603312
  55. [56]Huerta-Cepas J PhylomeDB v3.0: an expanding repository of genome-wide collections of trees, alignments and phylogeny-based orthology and paralogy predictions Nucleic Acids Res 39 D556 D560 2011 21075798 PMC3013701

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Authors
Gabaldón, T., & Koonin, E. V.
Affiliations
  • Universitat Pompeu Fabra (ES)
  • National Institutes of Health (US)
Corresponding author
  • Gabaldón, Toni
  • Koonin, Eugene V.
ORCID
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2013-04-04
Volume
14
Issue
5
Pages
360-366
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/nrg3456
PMC
PMC5877793
OpenAlex
W2041386815
Cited by
643
References
2
Citations by year
2026: 50 · 2025: 53 · 2024: 57 · 2023: 45 · 2022: 59 · 2021: 54 · 2020: 72 · 2019: 37 · 2018: 49 · 2017: 37 · 2016: 51 · 2015: 32 · 2014: 36 · 2013: 11
FWCI
4.10
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health and Human Services
  • Ministerio de Economía y Competitividad
  • National Institutes of Health
  • U.S. National Library of Medicine (Z01LM000073)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
gene orthology, homologous genes, gene function conservation, gene duplication, speciation, genotype-phenotype correlation, comparative genomics, gene function evolution
MeSH terms
Animals, Humans, Models, Genetic, Phenotype, Phylogeny, Sequence Analysis, Evolution, Molecular, Genomics, Models, Animal

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