Initial sequencing and analysis of the human genome - Vitagenes
Initial sequencing and analysis of the human genome - Vitagenes
Initial sequencing and analysis of the human genome - Vitagenes
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articlesaYW, F, VBr Br Ba Br Br Br Br Br Br Ba hmgARSC1/2* CG11375* *ZnfZnfbYEp1 Ep2 Ep1 Ep2 BrEp1PHDPHD*YPR031wWPHDPHDZnfF, H WF, HPHDPHDEp2 Br BMB Ch Ch SWI2 Sa hmg Ch Ch SWI2 SaPHDPHDPHDPHD*Lin-49**peregrin*CHD-3/T14G8.1 Mi-2cY, F, VEp1 Ep2E(Pc)-likeCommonancestorPHDPHDPHD2...5PHDPHDBrPHDhmgFsja* TrxW, F, HALRsjaCCCCCCSETSETCCA A A*Figure 42 Examples <strong>of</strong> domain accretion in chromatin proteins. Domain accretion invarious lineages before <strong>the</strong> animal divergence, in <strong>the</strong> apparent coelomate lineage <strong>and</strong> <strong>the</strong>vertebrate lineage are shown using schematic representations <strong>of</strong> domain architectures(not to scale). Asterisks, mobile domains that have participated in <strong>the</strong> accretion. Speciesin which a domain architecture has been identi®ed are indicated above <strong>the</strong> diagram(Y, yeast; W, worm; F, ¯y; V, vertebrate). Protein names are below <strong>the</strong> diagrams. TheMe*PHDPHDPHDHBrHrxPHDsja CCC SET Cdomains are SET, a chromatin protein methyltransferase domain; SWI2, a superfamily IIhelicase/ATPase domain; Sa, sant domain; Br, bromo domain; Ch, chromodomain; C, acysteine triad motif associated with <strong>the</strong> Msl-2 <strong>and</strong> SET domains; A, AT hook motif; EP1/EP2, enhancer <strong>of</strong> polycomb domains 1 <strong>and</strong> 2; Znf, zinc ®nger; sja, SET-JOR-associateddomain (L. Aravind, unpublished); Me, DNA methylase/Hrx-associated DNA binding zinc®nger; Ba, bromo-associated homology motif. a±c, Different examples <strong>of</strong> accretion.vertebrate innovation lies in <strong>the</strong> expansion <strong>of</strong> protein families. Table25 shows <strong>the</strong> most prevalent protein domains <strong>and</strong> protein familiesin <strong>human</strong>s, toge<strong>the</strong>r with <strong>the</strong>ir relative ranks in <strong>the</strong> o<strong>the</strong>r species.About 60% <strong>of</strong> families are more numerous in <strong>the</strong> <strong>human</strong> than in any<strong>of</strong> <strong>the</strong> o<strong>the</strong>r four organisms. This shows that gene duplication hasbeen a major evolutionary force during vertebrate evolution. Aab60102Conserved domain architectures in chromatin proteinsConserved domain architectures in apoptotic proteins3331816Human <strong>and</strong> flyHuman <strong>and</strong> wormWorm <strong>and</strong> flyAll threeHuman <strong>and</strong> flyHuman <strong>and</strong> wormWorm <strong>and</strong> flyAll threeFigure 43 Conservation <strong>of</strong> architectures between animal species. The pie charts illustrate<strong>the</strong> shared domain architectures <strong>of</strong> apparent orthologues that are conserved in at leasttwo <strong>of</strong> <strong>the</strong> three sequenced animal <strong>genome</strong>s. If an architecture was detected in fungi orplants, as well as two <strong>of</strong> <strong>the</strong> animal lineages, it was omitted as ancient <strong>and</strong> its absence in<strong>the</strong> third animal lineage attributed to gene loss. a, Chromatin-associated proteins.b, Components <strong>of</strong> <strong>the</strong> programmed cell death system.comparison <strong>of</strong> relative expansions in <strong>human</strong> versus ¯y is shown inFig. 44.Many <strong>of</strong> <strong>the</strong> families that are exp<strong>and</strong>ed in <strong>human</strong> relative to ¯y<strong>and</strong> worm are involved in distinctive aspects <strong>of</strong> vertebrate physiology.An example is <strong>the</strong> family <strong>of</strong> immunoglobulin (IG) domains,®rst identi®ed in antibodies thirty years ago. Classic (as opposed todivergent) IG domains are completely absent from <strong>the</strong> yeast <strong>and</strong>mustard weed proteomes <strong>and</strong>, although prokaryotic homologuesexist, <strong>the</strong>y have probably been transferred horizontally frommetazoans 341 . Most IG superfamily proteins in invertebrates arecell-surface proteins. In vertebrates, <strong>the</strong> IG repertoire includesimmune functions such as those <strong>of</strong> antibodies, MHC proteins,antibody receptors <strong>and</strong> many lymphocyte cell-surface proteins. Thelarge expansion <strong>of</strong> IG domains in vertebrates shows <strong>the</strong> versatility <strong>of</strong>a single family in evoking rapid <strong>and</strong> effective response to infection.Two prominent families are involved in <strong>the</strong> control <strong>of</strong> development.The <strong>human</strong> <strong>genome</strong> contains 30 ®broblast growth factors(FGFs), as opposed to two FGFs each in <strong>the</strong> ¯y <strong>and</strong> worm. Itcontains 42 transforming growth factor-bs(TGFbs) compared withnine <strong>and</strong> six in <strong>the</strong> ¯y <strong>and</strong> worm, respectively. These growth factorsare involved in organogenesis, such as that <strong>of</strong> <strong>the</strong> liver <strong>and</strong> <strong>the</strong> lung.A ¯y FGF protein, branchless, is involved in developing respiratoryorgans (tracheae) in embryos 342 . Thus, developmental triggers <strong>of</strong>morphogenesis in vertebrates have evolved from related but simplersystems in invertebrates 343 .Ano<strong>the</strong>r example is <strong>the</strong> family <strong>of</strong> intermediate ®lament proteins,with 127 family members. This expansion is almost entirely due to111 keratins, which are chordate-speci®c intermediate ®lamentproteins that form ®laments in epi<strong>the</strong>lia. The large number <strong>of</strong><strong>human</strong> keratins suggests multiple cellular structural support rolesfor <strong>the</strong> many specialized epi<strong>the</strong>lia <strong>of</strong> vertebrates.Finally, <strong>the</strong> olfactory receptor genes comprise a huge gene family<strong>of</strong> about 1,000 genes <strong>and</strong> pseudogenes 344,345 . The number <strong>of</strong> olfactoryreceptors testi®es to <strong>the</strong> importance <strong>of</strong> <strong>the</strong> sense <strong>of</strong> smell invertebrates. A total <strong>of</strong> 906 olfactory receptor genes <strong>and</strong> pseudogenescould be identi®ed in <strong>the</strong> draft <strong>genome</strong> sequence, two-thirds <strong>of</strong>which were not previously annotated. About 80% are found inabout two dozen clusters ranging from 6 to 138 genes <strong>and</strong> encompassingabout 30 Mb (,1%) <strong>of</strong> <strong>the</strong> <strong>human</strong> <strong>genome</strong>. Despite <strong>the</strong>importance <strong>of</strong> smell among our vertebrate ancestors, hominids906 © 2001 Macmillan Magazines Ltd NATURE | VOL 409 | 15 FEBRUARY 2001 | www.nature.com