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. 2013 Apr 18;496(7445):311-6.
doi: 10.1038/nature12027.

The African Coelacanth Genome Provides Insights Into Tetrapod Evolution

Chris T Amemiya  1 Jessica AlföldiAlison P LeeShaohua FanHervé PhilippeIain MaccallumIngo BraaschTereza ManousakiIgor SchneiderNicolas RohnerChris OrganDomitille ChalopinJeramiah J SmithMark RobinsonRosemary A DorringtonMarco GerdolBronwen AkenMaria Assunta BiscottiMarco BaruccaDenis BaurainAaron M BerlinGregory L BlatchFrancesco BuonocoreThorsten BurmesterMichael S CampbellAdriana CanapaJohn P CannonAlan ChristoffelsGianluca De MoroAdrienne L EdkinsLin FanAnna Maria FaustoNathalie FeinerMariko ForconiJunaid GamieldienSante GnerreAndreas GnirkeJared V GoldstoneWilfried HaertyMark E HahnUljana HesseSteve HoffmannJeremy JohnsonSibel I KarchnerShigehiro KurakuMarcia LaraJoshua Z LevinGary W LitmanEvan MauceliTsutomu MiyakeM Gail MuellerDavid R NelsonAnne NitscheEttore OlmoTatsuya OtaAlberto PallaviciniSumir PanjiBarbara PiconeChris P PontingSonja J ProhaskaDariusz PrzybylskiNil Ratan SahaVydianathan RaviFilipe J RibeiroTatjana Sauka-SpenglerGiuseppe ScapigliatiStephen M J SearleTed SharpeOleg SimakovPeter F StadlerJohn J StegemanKenta SumiyamaDiana TabbaaHakim TaferJason Turner-MaierPeter van HeusdenSimon WhiteLouise WilliamsMark YandellHenner BrinkmannJean-Nicolas VolffClifford J TabinNeil ShubinManfred SchartlDavid B JaffeJohn H PostlethwaitByrappa VenkateshFederica Di PalmaEric S LanderAxel MeyerKerstin Lindblad-Toh
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The African Coelacanth Genome Provides Insights Into Tetrapod Evolution

Chris T Amemiya et al. Nature. .
Free PMC article


The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.


Figure 1
Figure 1. A phylogenetic tree of a broad selection of jawed vertebrates shows that lungfish, not coelacanth, is the closest relative of tetrapods
Multiple sequence alignments of 251 genes present as 1-to-1 orthologs in 22 vertebrates and with a full sequence coverage for both lungfish and coelacanth were used to generate a concatenated matrix of 100,583 unambiguously aligned amino acid positions. The Bayesian tree was inferred using PhyloBayes under the CAT+GTR+Г4 model with confidence estimates derived from 100 jackknife tests (1.0 posterior probability) . The tree was rooted on cartilaginous fish. It shows both that lungfish is more closely related to tetrapods than coelacanth and that the protein sequence of coelacanth is slowly evolving.
Figure 2
Figure 2. Alignment of the HOX-D locus and upstream gene desert identifies conserved limb enhancers
(a) Organization of the mouse HOX-D locus and centromeric gene desert, flanked by the ATF2 and MTX2 genes. Limb regulatory sequences (I1, I2, I3, I4, CsB and CsC) are noted. Using the mouse locus as a reference (NCBI37/mm9 assembly), corresponding sequences from human, chicken, frog, coelacanth, pufferfish, medaka, stickleback, zebrafish and elephant shark were aligned. Alignment shows regions of homology between tetrapod, coelacanth and ray-finned fishes. (b) Alignment of vertebrate cis-regulatory elements I1, I2, I3, I4, CsB and CsC. (c) Expression patterns of coelacanth Island I in a transgenic mouse. Limb buds indicated by arrowheads in the first two panels. The third panel shows a close-up of a limb bud.
Figure 3
Figure 3. Phylogeny of CPS1 coding sequences used to determine positive selection within the urea cycle
Branch lengths are scaled to the expected number of substitutions/nucleotide and branch color indicates the strength of selection (dN/dS or ω) with red corresponding to positive or diversifying selection (ω > 5), blue to purifying selection (ω = 0), and yellow to neutral evolution (ω = 1). Thick branches indicate statistical support for evolution under episodic diversifying selection. The proportion of each color represents the fraction of the sequence undergoing the corresponding class of selection.
Figure 4
Figure 4. Transgenic analysis implicates involvement of Hox CNE HA14E1 in extraembryonic activities in the chick and mouse
(A) Chicken HA14E1 drives reporter expression in blood islands in chick embryos. A construct containing chicken HA14E1 upstream of a minimal (TK) promoter driving eGFP was electroporated in HH4 stage chick embryos together with a nuclear mCherry construct. GFP expression was analyzed at stage ~ HH11. The green aggregations and punctate staining are observed in the blood islands and developing vasculature. (B) Expression of Latimeria Hoxa14 reporter transgene in the developing placental labyrinth of a mouse embryo. A field of cells from the labyrinth region of an E8.5 embryo from a BAC transgenic line containing coelacanth Hoxa14-Hoxa9 in which the Hoxa14 gene had been supplanted with the gene for red fluorescence protein (RFP). Immunohistochemistry was used to detect RFP (brown staining in a small number of cells).

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