Trends in Genetics
Volume 20, Issue 10, October 2004, Pages 481-490
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Subfunction partitioning, the teleost radiation and the annotation of the human genome

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Half of all vertebrate species are teleost fish. What accounts for this explosion of biodiversity? Recent evidence and advances in evolutionary theory suggest that genomic features could have played a significant role in the teleost radiation. This review examines evidence for an ancient whole-genome duplication (tetraploidization) event that probably occurred just before the teleost radiation. The partitioning of ancestral subfunctions between gene copies arising from this duplication could have contributed to the genetic isolation of populations, to lineage-specific diversification of developmental programs, and ultimately to phenotypic variation among teleost fish. Beyond its importance for understanding mechanisms that generate biodiversity, the partitioning of subfunctions between teleost co-orthologs of human genes can facilitate the identification of tissue-specific conserved noncoding regions and can simplify the analysis of ancestral gene functions obscured by pleiotropy or haploinsufficiency. Applying these principles on a genomic scale can accelerate the functional annotation of the human genome and understanding of the roles of human genes in health and disease.

Section snippets

A genome duplication in the lineage of ray-finned fish

Pioneering studies revealed that zebrafish often has two orthologs (see Glossary) of human genes 4, 5 (for recent lists see Refs 6, 7). Genetic mapping studies showed that zebrafish co-orthologs (special types of paralogs) of human genes generally occupy duplicated segments on different zebrafish chromosomes 8, 9, 10, 11, 12, 13, 14, 15, 16, 17. Did most zebrafish duplicated chromosome segments arise by segmental duplication as in the human genome [18], or by genome duplication [19]? Consider,

When did genome duplication occur in the lineage of ray-finned fish?

The same early work that provided a mechanism for the expansion of zebrafish gene families also provided evidence as to when the duplication event took place 8, 9. Amores et al. [8] showed that among the four pufferfish (Fugu: Takifugu rubripes) Hox clusters known at the time [26], one was orthologous to the zebrafish hoxaa cluster, one to the hoxab cluster and the other two to the hoxba and hoxca clusters. This implied that the event that produced duplicate copies of zebrafish hox clusters

Evolution of gene duplicates in teleost fish

The teleost genome duplication presents previously unanticipated advantages for the analysis of gene function because of principles that govern the evolution of gene duplicates. After genome duplication, each gene copy can follow a separate evolutionary trajectory, little affected by unequal recombination or gene conversion, which homogenize tandem duplicates [48]. In the classical model [2], new gene duplicates face one of two fates: either one copy mutates to a pseudogene (called

Evidence for subfunction partitioning

Although it can be difficult to demonstrate that any particular pair of gene duplicates was retained by subfunctionalization, subfunction partitioning is common among duplicated genes arising from the preteleost genome duplication event. Subfunction partitioning can involve regulatory and/or structural subfunctions and has important evolutionary consequences. Assume, for instance, that an ancestral gene is expressed in liver and brain from independently mutable regulatory elements, and that

Nonfunctionalization, subfunction partitioning and lineage divergence

What has been the role of duplicate gene evolution in the teleost radiation? Different genes could have experienced nonfunctionalization in different teleost lineages (called divergent resolution in Ref. [73]). For example, the zebrafish lineage maintained two copies of the hoxc complex, but the pufferfish and medaka lineage retained just a single copy of the hoxccomplex, whereas the reverse is true for the hoxd complex 8, 29, 30, 45. An open question is to what extent such lineage-specific

Has subfunction partitioning occurred differently in various teleost lineages?

To evaluate the extent to which diverse teleost lineages have actually partitioned ancestral subfunctions differentially, we must examine the functions of both co-orthologs in more than one teleost. Gene expression patterns can serve as surrogates for regulatory subfunctions, but unfortunately, we know the detailed expression patterns of both duplicates in two different teleosts in very few cases. For MITF, most subfunctions appear to have partitioned before the divergence of zebrafish and

Subfunction partitioning can help identify genetic regulatory elements

Subfunction partitioning of teleost genes provides a special opportunity to identify tissue-specific regulatory elements. Because of the antiquity of their divergence, teleosts and tetrapod genome sequences have randomized except where function constrains sequence. Thus, conserved noncoding (CNC) sequences suggest functional genomic elements [78], and these sequences can be verified in functional tests [79]. Convenient computer programs are now available to identify CNC elements 80, 81. When

Subfunction partitioning in teleosts can facilitate analysis of gene function

Besides providing fundamental insights into the evolution of gene function, the origin of biodiversity, and analysis of conserved noncoding DNA, subfunction partitioning provides distinct advantages for functional genetic analyses. These include the identification of gene functions obscured in mammals by either pleiotropy or haploinsufficiency.

Many genes are essential at several developmental stages. Null mutations in such genes will block development at the stage of the earliest essential

Conclusions

Recent evidence converges on the conclusion that a genome duplication event preceded the grand radiation of teleosts into the most species-rich group of vertebrates. Subfunction partitioning could be a universal evolutionary pathway followed by co-orthologs resulting from this event, and perhaps by duplicated genes in general. It is still unclear how often teleost co-orthologs have partitioned subfunctions and how often they have evolved novel functions. A consequence of subfunction

Glossary

Allotetraploid:
a hybrid individual with two haploid genomes from one species and two haploid genomes from a different species.
Autotetraploid:
an individual with four haploid genomes all from the same species.
Co-orthologs:
a set of at least three genes in two species that are derived from a single gene in the last common ancestor of the two species, followed by gene duplication in the lineage of at least one of the species after the two species diverged. Co-orthology represents a special case of

References (95)

  • W.P Yu

    Duplication, degeneration and subfunctionalization of the nested synapsin-Timp genes in Fugu

    Trends Genet.

    (2003)
  • J.G. Inoue

    Basal actinopterygian relationships: a mitogenomic perspective on the phylogeny of the ‘ancient fish’

    Mol. Phylogenet. Evol.

    (2003)
  • G.J. Graham

    Tandem genes and clustered genes

    J. Theor. Biol.

    (1995)
  • J. Lister

    Duplicate mitf genes in zebrafish: complementary expression and conservation of melanogenic potential

    Dev. Biol.

    (2001)
  • E.F. Chiang

    Two sox9 genes on duplicated zebrafish chromosomes: expression of similar transcription activators in distinct sites

    Dev. Biol.

    (2001)
  • T. Udono

    Structural organization of the human microphthalmia-associated transcription factor gene containing four alternative promoters

    Biochim. Biophys. Acta

    (2000)
  • S. Nornes

    Zebrafish contains two Pax6 genes involved in eye development

    Mech. Dev.

    (1998)
  • K. Okubo

    A novel third gonadotropin-releasing hormone receptor in the medaka Oryzias latipes: evolutionary and functional implications

    Gene

    (2003)
  • H. Pöpperl

    Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx

    Cell

    (1995)
  • J.S. Taylor

    Genome duplication, divergent resolution and speciation

    Trends Genet.

    (2001)
  • J.S. Nelson

    Fishes of the World

    (1994)
  • S. Ohno

    Evolution by Gene Duplication

    (1970)
  • C. Ohno

    Ancient linkage groups and frozen accidents

    Nature

    (1973)
  • M. Ekker

    Coordinate embryonic expression of three zebrafish engrailed genes

    Development

    (1992)
  • V.E. Prince

    Zebrafish hox genes: genomic organization and modified colinear expression patterns in the trunk

    Development

    (1998)
  • Y. Van de Peer

    Wanda: a database of duplicated fish genes

    Nucleic Acids Res

    (2002)
  • Postlethwait, J. Fish Development and Genetics: The Zebrafish and Medaka Models (Korzh, Z.G.a.V., ed.), World...
  • A. Amores

    Zebrafish hox clusters and vertebrate genome evolution

    Science

    (1998)
  • J. Postlethwait

    Vertebrate genome evolution and the zebrafish gene map

    Nat. Genet.

    (1998)
  • M.A. Gates

    A genetic linkage map for zebrafish: comparative analysis and localization of genes and expressed sequences

    Genome Res.

    (1999)
  • W.B. Barbazuk

    The syntenic relationship of the zebrafish and human genomes

    Genome Res.

    (2000)
  • J.H. Postlethwait

    Zebrafish comparative genomics and the origins of vertebrate chromosomes

    Genome Res.

    (2000)
  • I.G. Woods

    A comparative map of the zebrafish genome

    Genome Res.

    (2000)
  • J.S. Taylor

    Comparative genomics provides evidence for an ancient genome duplication event in fish

    Philos. Trans. R. Soc. Lond. B Biol. Sci

    (2001)
  • Postlethwait, J. et al. (2002) Duplication of a portion of human chromosome 20q containing Topoisomerase (Top1) and...
  • J. Taylor

    Genome duplication, a trait shared by 22,000 species of ray-finned fish

    Genome Res.

    (2003)
  • D.P. Locke

    Large-scale variation among human and great ape genomes determined by array comparative genomic hybridization

    Genome Res.

    (2003)
  • R. Phillips et al.

    Chromosome evolution in the Salmonidae (Pisces): an update

    Biol. Rev. Camb. Philos. Soc.

    (2001)
  • L. David

    Recent duplication of the common carp (Cyprinus carpio L.) genome as revealed by analyses of microsatellite loci

    Mol. Biol. Evol.

    (2003)
  • J. Wittbrodt

    More genes in fish?

    BioEssays

    (1998)
  • B.S. Gaut et al.

    DNA sequence evidence for the segmental allotetraploid origin of maize

    Proc. Natl. Acad. Sci. U. S. A.

    (1997)
  • S. Aparicio

    Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution of vertebrate Hox complexes

    Nat. Genet.

    (1997)
  • G. Vogel

    Doubled genes may explain fish diversity

    Science

    (1998)
  • S. Aparicio

    Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes

    Science

    (2002)
  • A. Amores

    Developmental roles of pufferfish Hox clusters and genome evolution in ray-fin fish

    Genome Res.

    (2004)
  • S.F. Smith

    Analyses of the extent of shared synteny and conserved gene orders between the genome of Fugu rubripes and human 20q

    Genome Res.

    (2002)
  • J. Altschmied

    Subfunctionalization of duplicate mitf genes associated with differential degeneration of alternative exons in fish

    Genetics

    (2002)
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