Jump to content

2R hypothesis

From Wikipedia, the free encyclopedia

The2R hypothesisorOhno's hypothesis,first proposed bySusumu Ohnoin 1970,[1]is ahypothesisthat the genomes of the earlyvertebratelineage underwent two wholegenome duplications,and thus modern vertebrate genomes reflectpaleopolyploidy.The name derives from the2 roundsof duplication originally hypothesized by Ohno, but refined in a 1994 version, and the term2R hypothesiswas probably coined in 1999. Variations in the number and timings of genome duplications typically still are referred to as examples of the 2R hypothesis.[2]

The 2R hypothesis has been the subject of much research and controversy; however, with growing support from genome data, including thehuman genome,the balance of opinion has shifted strongly in favour of support for the hypothesis. According to Karsten Hokamp,Aoife McLysaghtandKenneth H. Wolfe,[2]the version of the genome duplication hypothesis from which 2R hypothesis takes its name appears in Hollandet al.[3]and the term was coined by Austin L. Hughes.[4]

Ohno's argument[edit]

Ohno presented the first version of the 2R hypothesis as part of his larger argument for the general importance ofgene duplicationinevolution.Based on relative genome sizes andisozymeanalysis, he suggested that ancestral fish or amphibians had undergone at least one and possibly more cases of "tetraploid evolution". He later added to this argument the evidence that mostparalogous genesin vertebrates do not demonstrategenetic linkage.Ohno argued that linkage should be expected in the case of individualtandem duplications(in which a duplicate gene is added adjacent to the original gene on the same chromosome), but not in the case of chromosome duplications.[5]

Later evidence[edit]

In 1977, Schmidtke and colleagues showed thatisozymecomplexity is similar inlanceletsandtunicates,contradicting a prediction of Ohno's hypothesis thatgenome duplicationoccurred in the common ancestor of lancelets andvertebrates.[6]However, this analysis did not examine vertebrates, so could say nothing about later duplication events.[7](Furthermore, much latermolecular phylogeneticshas shown that vertebrates are more closely related to tunicates than to lancelets, thus negating the logic of this analysis.[8]) The 2R hypothesis saw a resurgence of interest in the 1990s for two reasons. First, gene mapping data in humans and mice revealed extensiveparalogy regions- sets of genes on one chromosome related to sets of genes on another chromosome in the same species, indicative of duplication events in evolution.[9]Paralogy regions were generally in sets of four. Second, cloning ofHox genesin lancelet revealed presence of a singleHox gene cluster,[10]in contrast to the four clusters in humans and mice. Data from additionalgene familiesrevealed a common one-to-many rule when lancelet and vertebrate genes were compared.[7]Taken together, these two lines of evidence suggest that two genome duplications occurred in the ancestry of vertebrates, after it had diverged from thecephalochordateevolutionary lineage.

Pattern predicted for the relative locations of paralogous genes from two genome duplications[11]

Controversy about the 2R hypothesis hinged on the nature ofparalogy regions.It is not disputed that humanchromosomesbear sets of genes related to sets of genes on other chromosomes; the controversy centres on whether they were generated by large-scale duplications that doubled all the genes at the same time, or whether a series of individualgene duplicationsoccurred followed bychromosomal rearrangementto shuffle sets of genes together. Hughes and colleagues found thatphylogenetic treesbuilt from differentgene familieswithinparalogy regionshad different shapes, suggesting that the gene families had different evolutionary histories.[12][13]This was suggested to be inconsistent with the 2R hypothesis. However, other researchers have argued that such 'topology tests' do not test 2R rigorously, becauserecombinationcould have occurred between the closely related chromosomes generated bypolyploidy,[14][15]because inappropriate genes had been compared[16]and because different predictions are made if genome duplication occurred throughhybridisationbetween species.[17]In addition, several researchers were able to date duplications of gene families withinparalogy regionsconsistently to the early evolution of vertebrates, after divergence from amphioxus, consistent with the 2R hypothesis.[18][19]When completegenome sequencesbecame available for vertebrates,Ciona intestinalisand lancelets, it was found that much of thehuman genomewas arranged inparalogy regionsthat could be traced to large-scale duplications,[20]and that these duplications occurred after vertebrates had diverged fromtunicates[11]and lancelets.[21]This would date the two genome duplications to between 550 and 450 million years ago.

The controversy raging in the late 1990s was summarized in a 2001 review of the subject by Wojciech Makałowski, who stated that "the hypothesis of whole genome duplications in the early stages of vertebrate evolution has as many adherents as opponents".[5]

In contrast, a more recent review in 2007 by Masanori Kasahara states that there is now "incontrovertible evidence supporting the 2R hypothesis" and that "a long-standing debate on the 2R hypothesis is approaching the end".[22]Michael Benton,in the 2014 edition ofVertebrate Palaeontology,states, "It turns out that, in places whereamphioxushas a single gene, vertebrates often have two, three, or four equivalent genes as a result of two intervening whole-genome duplication events. "[23]

Ohnology[edit]

Ohnologous genes are paralogousgenesthat have originated by a process of this 2Rduplication.The name was first given in honour ofSusumu OhnobyKen Wolfe.[24]It is useful for evolutionary analysis because all ohnologues in a genome have been diverging for the same length of time (since their common origin in the whole genome duplication).[25][26]

Well-studied ohnologous genes include genes in human chromosome 2, 7, 12 and 17 containingHox geneclusters,collagengenes,keratingenes and other duplicated genes,[27]genes in human chromosomes 4, 5, 8 and 10 containing neuropeptide receptor genes, NK classhomeobox genesand many moregene families,[28][29][30]and parts of human chromosomes 13, 4, 5 and X containing theParaHoxgenes and their neighbors.[31]TheMajor histocompatibility complex(MHC) on human chromosome 6 has paralogy regions on chromosomes 1, 9 and 19.[32]Much of thehuman genomeseems to be assignable to paralogy regions.[33]

References[edit]

  1. ^Ohno, Susumu (1970).Evolution by Gene Duplication.London: Allen and Unwin,ISBN0-04-575015-7.
  2. ^abHokamp, K;McLysaght, A;Wolfe, KH(2003). "The 2R hypothesis and the human genome sequence".Journal of Structural and Functional Genomics.3(1–4): 95–110.doi:10.1023/A:1022661917301.PMID12836689.S2CID18856088.
  3. ^Holland, PW; Garcia-Fernàndez, J; Williams, NA; Sidow, A (1994). "Gene duplications and the origins of vertebrate development".Development. Supplement:125–33.PMID7579513.
  4. ^Hughes, Austin L. (1999). "Phylogenies of developmentally important proteins do not support the hypothesis of two rounds of genome duplication early in vertebrate history".Journal of Molecular Evolution.48(5): 565–76.Bibcode:1999JMolE..48..565H.doi:10.1007/PL00006499.PMID10198122.S2CID24897399.
  5. ^abMakalowski, Wojciech (2001)."Are we polyploids? A brief history of one hypothesis".Genome Research.11(5): 667–70.doi:10.1101/gr.188801.PMID11337465.Free access icon
  6. ^Schmidtke, Jörg; Weiler, Conrad; Kunz, Brigitte; Engel, Wolfgang (1977). "Isozymes of a tunicate and a cephalochordate as a test of polyploidisation in chordate evolution".Nature.266(5602): 532–533.Bibcode:1977Natur.266..532S.doi:10.1038/266532a0.PMID859619.S2CID4255382.
  7. ^abHolland, PW (2003). "More genes in vertebrates?".Journal of Structural and Functional Genomics.3(1–4): 75–84.doi:10.1023/a:1022656931587.PMID12836687.S2CID35418674.Closed access icon
  8. ^Delsuc, F; Brinkmann, H; Chourrout, D; Philippe, H (2006)."Tunicates and not cephalochordates are the closest living relatives of vertebrates"(PDF).Nature.439(7079): 965–8.Bibcode:2006Natur.439..965D.doi:10.1038/nature04336.PMID16495997.S2CID4382758.Closed access icon
  9. ^Lundin, LG (April 1993). "Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse".Genomics.16(1): 1–19.doi:10.1006/geno.1993.1133.PMID8486346.
  10. ^Garcia-Fernández, J; Holland, PW (Aug 18, 1994). "Archetypal organization of the amphioxus Hox gene cluster".Nature.370(6490): 563–6.Bibcode:1994Natur.370..563G.doi:10.1038/370563a0.PMID7914353.S2CID4329696.
  11. ^abDehal, Paramvir; Boore, Jeffrey L. (2005)."Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate".PLOS Biology.3(10): e314.doi:10.1371/journal.pbio.0030314.PMC1197285.PMID16128622.Open access icon
  12. ^Hughes, AL (May 1999). "Phylogenies of developmentally important proteins do not support the hypothesis of two rounds of genome duplication early in vertebrate history".Journal of Molecular Evolution.48(5): 565–76.Bibcode:1999JMolE..48..565H.doi:10.1007/PL00006499.PMID10198122.S2CID24897399.
  13. ^Hughes, Austin L.; Friedman, Robert (2003)."2R or not 2R: Testing hypotheses of genome duplication in early vertebrates".Journal of Structural and Functional Genomics.3(1/4): 85–93.doi:10.1023/A:1022681600462.PMID12836688.S2CID835565.
  14. ^Furlong, RF; Holland, PW (2002)."Were vertebrates octoploid?".Philosophical Transactions of the Royal Society B.357(1420): 531–44.doi:10.1098/rstb.2001.1035.PMC1692965.PMID12028790.
  15. ^Lynch, VJ; Wagner, GP (2009)."Multiple chromosomal rearrangements structured the ancestral vertebrate Hox-bearing protochromosomes".PLOS Genetics.5(1): e1000349.doi:10.1371/journal.pgen.1000349.PMC2622764.PMID19165336.Open access icon
  16. ^Larhammar, D.; Josephson, M (2002)."The Human Hox-bearing Chromosome Regions Did Arise by Block or Chromosome (or Even Genome) Duplications".Genome Research.12(1): 1910–1920.doi:10.1101/gr.445702.PMC187569.PMID12466295.
  17. ^Spring, Jürg (1997)."Vertebrate evolution by interspecific hybridisation – are we polyploid?".FEBS Letters.400(1): 2–8.doi:10.1016/S0014-5793(96)01351-8.PMID9000502.Free access icon
  18. ^Abi-Rached, L; Gilles, A; Shiina, T; Pontarotti, P; Inoko, H (2002)."Evidence of en bloc duplication in vertebrate genomes".Nature Genetics.31(1): 100–5.doi:10.1038/ng855.PMID11967531.S2CID8516649.
  19. ^Castro, LF; Holland, PW (Sep–Oct 2003). "Chromosomal mapping of ANTP class homeobox genes in amphioxus: piecing together ancestral genomes".Evolution & Development.5(5): 459–65.doi:10.1046/j.1525-142x.2003.03052.x.PMID12950625.S2CID38083087.
  20. ^McLysaght, Aoife;Hokamp, Karsten;Wolfe, Kenneth H.(2002). "Extensive genomic duplication during early chordate evolution".Nature Genetics.31(2): 200–204.doi:10.1038/ng884.PMID12032567.S2CID8263376.
  21. ^Putnam, NH; Butts, T; Ferrier, DE; Furlong, RF; Hellsten, U; Kawashima, T; Robinson-Rechavi, M; Shoguchi, E; Terry, A; Yu, JK; Benito-Gutiérrez, EL; Dubchak, I; Garcia-Fernàndez, J; Gibson-Brown, JJ; Grigoriev, IV; Horton, AC; de Jong, PJ; Jurka, J; Kapitonov, VV; Kohara, Y; Kuroki, Y; Lindquist, E; Lucas, S; Osoegawa, K; Pennacchio, LA; Salamov, AA; Satou, Y; Sauka-Spengler, T; Schmutz, J; Shin-I, T; Toyoda, A; Bronner-Fraser, M; Fujiyama, A; Holland, LZ; Holland, PW; Satoh, N; Rokhsar, DS (2008)."The amphioxus genome and the evolution of the chordate karyotype".Nature.453(7198): 1064–71.Bibcode:2008Natur.453.1064P.doi:10.1038/nature06967.PMID18563158.
  22. ^Kasahara, Masanori (2007). "The 2R hypothesis: an update".Current Opinion in Immunology.19(5): 547–52.doi:10.1016/j.coi.2007.07.009.PMID17707623.Closed access icon
  23. ^Benton, Michael(2014).Vertebrate Palaeontology.Wiley. p. 92.ISBN978-1-118-40764-6.Retrieved19 December2015.
  24. ^Wolfe K (May 2000). "Robustness--it's not where you think it is".Nature Genetics.25(1): 3–4.doi:10.1038/75560.PMID10802639.S2CID85257685.
  25. ^McLysaght A, Makino T, Grayton HM, Tropeano M, Mitchell KJ, Vassos E, Collier DA (January 2014)."Ohnologs are overrepresented in pathogenic copy number mutations".Proceedings of the National Academy of Sciences of the United States of America.111(1): 361–6.Bibcode:2014PNAS..111..361M.doi:10.1073/pnas.1309324111.PMC3890797.PMID24368850.
  26. ^Makino T, McLysaght A (May 2010)."Ohnologs in the human genome are dosage balanced and frequently associated with disease".Proceedings of the National Academy of Sciences of the United States of America.107(20): 9270–4.Bibcode:2010PNAS..107.9270M.doi:10.1073/pnas.0914697107.PMC2889102.PMID20439718.
  27. ^Ruddle FH, Bentley KL, Murtha MT, Risch N (1994). "Gene loss and gain in the evolution of the vertebrates".Development.1994:155–61.doi:10.1242/dev.1994.Supplement.155.PMID7579516.
  28. ^Pébusque MJ, Coulier F, Birnbaum D, Pontarotti P (September 1998)."Ancient large-scale genome duplications: phylogenetic and linkage analyses shed light on chordate genome evolution".Molecular Biology and Evolution.15(9): 1145–59.doi:10.1093/oxfordjournals.molbev.a026022.PMID9729879.
  29. ^Larsson TA, Olsson F, Sundstrom G, Lundin LG, Brenner S, Venkatesh B, Larhammar D (June 2008)."Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions".BMC Evolutionary Biology.8(1): 184.Bibcode:2008BMCEE...8..184L.doi:10.1186/1471-2148-8-184.PMC2453138.PMID18578868.
  30. ^Pollard SL, Holland PW (September 2000)."Evidence for 14 homeobox gene clusters in human genome ancestry".Current Biology.10(17): 1059–62.doi:10.1016/S0960-9822(00)00676-X.PMID10996074.S2CID32135432.
  31. ^Mulley JF, Chiu CH, Holland PW (July 2006)."Breakup of a homeobox cluster after genome duplication in teleosts".Proceedings of the National Academy of Sciences of the United States of America.103(27): 10369–10372.Bibcode:2006PNAS..10310369M.doi:10.1073/pnas.0600341103.PMC1502464.PMID16801555.
  32. ^Flajnik MF, Kasahara M (September 2001)."Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system".Immunity.15(3): 351–62.doi:10.1016/S1074-7613(01)00198-4.PMID11567626.
  33. ^McLysaght A, Hokamp K, Wolfe KH (June 2002). "Extensive genomic duplication during early chordate evolution".Nature Genetics.31(2): 200–4.doi:10.1038/ng884.PMID12032567.S2CID8263376.
Retrieved from "https://en.wikipedia.org/w/index.php?title=2R_hypothesis&oldid=1226233710"