2R hypothesis

Last updated

The 2R hypothesis or Ohno's hypothesis, first proposed by Susumu Ohno in 1970, [1] is a hypothesis that the genomes of the early vertebrate lineage underwent two whole genome duplications, and thus modern vertebrate genomes reflect paleopolyploidy. The name derives from the 2 rounds of duplication originally hypothesized by Ohno, but refined in a 1994 version, and the term 2R hypothesis was 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]

Contents

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

Ohno's argument

Ohno presented the first version of the 2R hypothesis as part of his larger argument for the general importance of gene duplication in evolution. Based on relative genome sizes and isozyme analysis, 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 most paralogous genes in vertebrates do not demonstrate genetic linkage. Ohno argued that linkage should be expected in the case of individual tandem 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

In 1977, Schmidtke and colleagues showed that isozyme complexity is similar in lancelets and tunicates, contradicting a prediction of Ohno's hypothesis that genome duplication occurred in the common ancestor of lancelets and vertebrates. [6] However, this analysis did not examine vertebrates, so could say nothing about later duplication events. [7] (Furthermore, much later molecular phylogenetics has 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 extensive paralogy 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 of Hox genes in lancelet revealed presence of a single Hox gene cluster, [10] in contrast to the four clusters in humans and mice. Data from additional gene families revealed 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 the cephalochordate evolutionary lineage.

Pattern predicted for the relative locations of paralogous genes from two genome duplications Patro de gens - Hipotesi 2R.png
Pattern predicted for the relative locations of paralogous genes from two genome duplications

Controversy about the 2R hypothesis hinged on the nature of paralogy regions. It is not disputed that human chromosomes bear 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 individual gene duplications occurred followed by chromosomal rearrangement to shuffle sets of genes together. Hughes and colleagues found that phylogenetic trees built from different gene families within paralogy regions had 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, because recombination could have occurred between the closely related chromosomes generated by polyploidy, [14] [15] because inappropriate genes had been compared [16] and because different predictions are made if genome duplication occurred through hybridisation between species. [17] In addition, several researchers were able to date duplications of gene families within paralogy regions consistently to the early evolution of vertebrates, after divergence from amphioxus, consistent with the 2R hypothesis. [18] [19] When complete genome sequences became available for vertebrates, Ciona intestinalis and lancelets, it was found that much of the human genome was arranged in paralogy regions that could be traced to large-scale duplications, [20] and that these duplications occurred after vertebrates had diverged from tunicates [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 of Vertebrate Palaeontology , states, "It turns out that, in places where amphioxus has a single gene, vertebrates often have two, three, or four equivalent genes as a result of two intervening whole-genome duplication events." [23]

Ohnology

Ohnologous genes are paralogous genes that have originated by a process of this 2R duplication. The name was first given in honour of Susumu Ohno by Ken 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 containing Hox gene clusters, collagen genes, keratin genes and other duplicated genes, [27] genes in human chromosomes 4, 5, 8 and 10 containing neuropeptide receptor genes, NK class homeobox genes and many more gene families, [28] [29] [30] and parts of human chromosomes 13, 4, 5 and X containing the ParaHox genes and their neighbors. [31] The Major histocompatibility complex (MHC) on human chromosome 6 has paralogy regions on chromosomes 1, 9 and 19. [32] Much of the human genome seems to be assignable to paralogy regions. [33]

Related Research Articles

<span class="mw-page-title-main">Chordate</span> Phylum of animals having a dorsal nerve cord

A chordate is a deuterostomic animal belonging to the phylum Chordata. All chordates possess, at some point during their larval or adult stages, five distinctive physical characteristics (synapomorphies) that distinguish them from other taxa. These five synapomorphies are a notochord, a hollow dorsal nerve cord, an endostyle or thyroid, pharyngeal slits, and a post-anal tail. The name "chordate" comes from the first of these synapomorphies, the notochord, which plays a significant role in chordate body plan structuring and movements. Chordates are also bilaterally symmetric, have a coelom, possess a closed circulatory system, and exhibit metameric segmentation.

<span class="mw-page-title-main">Craniate</span> Clade of chordates, member of the Craniata

A craniate is a member of the Craniata, a proposed clade of chordate animals with a skull of hard bone or cartilage. Living representatives are the Myxini (hagfishes), Hyperoartia, and the much more numerous Gnathostomata. Formerly distinct from vertebrates by excluding hagfish, molecular and anatomical research in the 21st century has led to the reinclusion of hagfish as vertebrates, making living craniates synonymous with living vertebrates.

Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

<span class="mw-page-title-main">Lancelet</span> Order of chordates

The lancelets, also known as amphioxi, consist of some 30 to 35 species of "fish-like" benthic filter feeding chordates in the subphylum Cephalochordata, class Leptocardii, and family Branchiostomatidae.

<span class="mw-page-title-main">Sequence homology</span> Shared ancestry between DNA, RNA or protein sequences

Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal gene transfer event (xenologs).

The ParaHox gene cluster is an array of homeobox genes from the Gsx, Xlox (Pdx) and Cdx gene families.

<span class="mw-page-title-main">Paleopolyploidy</span> State of having undergone whole genome duplication in deep evolutionary time

Paleopolyploidy is the result of genome duplications which occurred at least several million years ago (MYA). Such an event could either double the genome of a single species (autopolyploidy) or combine those of two species (allopolyploidy). Because of functional redundancy, genes are rapidly silenced or lost from the duplicated genomes. Most paleopolyploids, through evolutionary time, have lost their polyploid status through a process called diploidization, and are currently considered diploids, e.g., baker's yeast, Arabidopsis thaliana, and perhaps humans.

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

<i>Ciona intestinalis</i> Species of ascidian

Ciona intestinalis is an ascidian, a tunicate with very soft tunic. Its Latin name literally means "pillar of intestines", referring to the fact that its body is a soft, translucent column-like structure, resembling a mass of intestines sprouting from a rock. It is a globally distributed cosmopolitan species. Since Linnaeus described the species, Ciona intestinalis has been used as a model invertebrate chordate in developmental biology and genomics. Studies conducted between 2005 and 2010 have shown that there are at least two, possibly four, sister species. More recently it has been shown that one of these species has already been described as Ciona robusta. By anthropogenic means, the species has invaded various parts of the world and is known as an invasive species.

Susumu Ohno was a Japanese-American geneticist and evolutionary biologist, and seminal researcher in the field of molecular evolution.

<span class="mw-page-title-main">Gene cluster</span>

A gene family is a set of homologous genes within one organism. A gene cluster is a group of two or more genes found within an organism's DNA that encode similar polypeptides, or proteins, which collectively share a generalized function and are often located within a few thousand base pairs of each other. The size of gene clusters can vary significantly, from a few genes to several hundred genes. Portions of the DNA sequence of each gene within a gene cluster are found to be identical; however, the resulting protein of each gene is distinctive from the resulting protein of another gene within the cluster. Genes found in a gene cluster may be observed near one another on the same chromosome or on different, but homologous chromosomes. An example of a gene cluster is the Hox gene, which is made up of eight genes and is part of the Homeobox gene family.

Myogenic regulatory factors (MRF) are basic helix-loop-helix (bHLH) transcription factors that regulate myogenesis: MyoD, Myf5, myogenin, and MRF4.

Chordate genomics is the study of the evolution of the chordate clade based on a comparison of the genomes of several species within the clade. The field depends on whole genome data of organisms. It uses comparisons of synteny blocks, chromosome translocation, and other genomic rearrangements to determine the evolutionary history of the clade, and to reconstruct the genome of the founding species.

Branchiostoma floridae, the Florida lancelet, is a lancelet of the genus Branchiostoma. The genome of this species has been sequenced, revealing that among the chordates, the morphologically simpler tunicates are actually more closely related to vertebrates than lancelets. An embryo of a Florida amphioxus has a larval pharynx with gill slits that is asymmetrical. The gill slits in the larval pharynx form in the center of the embryo when it is in its earliest stage of development (primordial) meaning the thick layer of endoderm is overlapped by a thin layer; which aids into making the B. floridae asymmetrical from left to right. The lancelet Branchiostoma floridae maintains a high level of Fox transcription factor gene diversity, with 32 distinct Fox genes in its genome, and 21,229 clusters of cDNA clones, making it very useful to the research community.

<span class="mw-page-title-main">Relaxin family peptide hormones</span> Protein family

Relaxin family peptide hormones in humans are represented by seven members: three relaxin-like (RLN) and four insulin-like (INSL) peptides: RLN1, RLN2, RNL3, INSL3, INSL4, INSL5, INSL6. This subdivision into two classes is based primarily on early findings, and does not reflect the evolutionary origins or physiological differences between peptides. For example, it is known that the genes coding for RLN3 and INSL5 arose from one ancestral gene, and INSL3 shares origin with RLN2 and its multiple duplicates: RLN1, INSL4, INSL6.

<span class="mw-page-title-main">Olfactores</span> Clade of animals comprising vertebrates and tunicates

Olfactores is a clade within the Chordata that comprises the Tunicata (Urochordata) and the Vertebrata. Olfactores represent the overwhelming majority of the phylum Chordata, as the Cephalochordata are the only chordates not included in the clade. This clade is defined by a more advanced olfactory system which, in the immediate vertebrate generation, caused the appearance of nostrils.

<span class="mw-page-title-main">Kenneth H. Wolfe</span> Irish geneticist and academic

Kenneth Henry Wolfe is an Irish geneticist and professor of genomic evolution at University College Dublin (UCD), Ireland.

<span class="mw-page-title-main">Aoife McLysaght</span> Irish geneticist and professor

Aoife McLysaght is an Irish geneticist and a professor in the Molecular Evolution Laboratory of the Smurfit Institute of Genetics, Trinity College Dublin in Ireland.

Cytochrome P450, family 11, also known as CYP11, is a chordate cytochrome P450 monooxygenase family. This family contains many enzymes involved in steroidogenesis, such as Cholesterol side-chain cleavage enzyme (CYP11A1), Steroid 11β-hydroxylase (CYP11B1) and Aldosterone synthase (CYP11B2). CYP11 can be divided into A to E five subfamilies, and CYP11A are the ohonologues to CYP11C, which duplicated during 2R event, and the tetrapod's CYP11B evolved from CYP11C of its fish ancestors, CYP11D and F found in amphioxus. These are not the typical CYP subfamilies, which share at least 40% amino acid identity, members between CYP11A and B subfamily are only 37.5-38.8% identical, and the CYP11D and E genes seen in modern lancelet is 39% identical to catfish CYP11A1.

Linda Zimmerman Holland is a research biologist at Scripps Institution of Oceanography known for her work examining the evolution of vertebrates.

References

  1. ↑ Ohno, Susumu (1970). Evolution by Gene Duplication. London: Allen and Unwin, ISBN   0-04-575015-7.
  2. 1 2 Hokamp, 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. PMID   12836689. S2CID   18856088.
  3. ↑ Holland, PW; Garcia-Fernàndez, J; Williams, NA; Sidow, A (1994). "Gene duplications and the origins of vertebrate development". Development. Supplement: 125–33. PMID   7579513.
  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. PMID   10198122. S2CID   24897399.
  5. 1 2 Makalowski, Wojciech (2001). "Are we polyploids? A brief history of one hypothesis". Genome Research . 11 (5): 667–70. doi: 10.1101/gr.188801 . PMID   11337465. Lock-green.svg
  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. PMID   859619. S2CID   4255382.
  7. 1 2 Holland, PW (2003). "More genes in vertebrates?". Journal of Structural and Functional Genomics. 3 (1–4): 75–84. doi:10.1023/a:1022656931587. PMID   12836687. S2CID   35418674. Closed Access logo transparent.svg
  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. PMID   16495997. S2CID   4382758. Closed Access logo transparent.svg
  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. PMID   8486346.
  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. PMID   7914353. S2CID   4329696.
  11. 1 2 Dehal, 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 . PMC   1197285 . PMID   16128622. Open Access logo PLoS transparent.svg
  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. PMID   10198122. S2CID   24897399.
  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. PMID   12836688. S2CID   835565.
  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. PMC   1692965 . PMID   12028790.
  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 . PMC   2622764 . PMID   19165336. Open Access logo PLoS transparent.svg
  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. PMC   187569 . PMID   12466295.
  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 . PMID   9000502. Lock-green.svg
  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 . PMID   11967531. S2CID   8516649.
  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. PMID   12950625. S2CID   38083087.
  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. PMID   12032567. S2CID   8263376.
  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 . PMID   18563158.
  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. PMID   17707623. Closed Access logo transparent.svg
  23. ↑ Benton, Michael (2014). Vertebrate Palaeontology. Wiley. p. 92. ISBN   978-1-118-40764-6 . Retrieved 19 December 2015.
  24. ↑ Wolfe K (May 2000). "Robustness--it's not where you think it is". Nature Genetics. 25 (1): 3–4. doi:10.1038/75560. PMID   10802639. S2CID   85257685.
  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 . PMC   3890797 . PMID   24368850.
  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 . PMC   2889102 . PMID   20439718.
  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. PMID   7579516.
  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 . PMID   9729879.
  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 . PMC   2453138 . PMID   18578868.
  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 . PMID   10996074. S2CID   32135432.
  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 . PMC   1502464 . PMID   16801555.
  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 . PMID   11567626.
  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. PMID   12032567. S2CID   8263376.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.