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Linking Teleost Fish Genomes to Human Biology: Spotted Gar.

John Postlethwait
Department of Biology
Institute of Neuroscience University of Oregon
Eugene, OR - USA

Short Profile

Postlethwait’s  laboratory is interested in the genetic regulation of animal development including development of the nervous system, the mechanisms of sex determination, the origin of novel morphologies in evolution and the evolution of the vertebrate genome.
They investigate several aspects of this main problem:
MicroRNAs: The roles of microRNAs in embryonic (especially skeletal) development, including evolving miRNA functions after genome duplication.
Icefish: The genetic basis for the evolution of osteopenia or osteoporosis in Antarctic icefish.
Speciation: The roles of genome duplication in lineage divergence, focusing on the evolution of cis and trans acting regulation in the radiation of the danio lineage, including zebrafish, and on variation among populations of stickleback.
Oikopleura: Retaining a chordate body plan as an adult, the larvacean urochordate Oikopleura dioica represents the sister lineage to the vertebrates, diverging before the R1 and R2 rounds of genome duplication that led to the origin of vertebrate innovations.

Reference Student: Ugo Coppola (ph. 345)

Selected Bibliography for PhD Students:

Allan Force et al., 1999. Preservation of Duplicate Genes by Complementary, Degenerative Mutations. Genetics 151: 1531–1545.

Braasch I, Peterson SM, Desvignes T, McCluskey BM, Batzel P, Postlethwait JH. (2015) A new model army: Emerging fish models to study the genomics of vertebrate Evo-Devo. J Exp Zool B Mol Dev Evol. 324:316-41. doi: 10.1002/jez.b.22589.

Ingo Braasch et al. Linking human biology to fish models: Sequence of the spotted gar genome. NGSubmission.

Selected Publications

Braasch I, Peterson SM, Desvignes T, McCluskey BM, Batzel P, Postlethwait JH. (2015) A new model army: Emerging fish models to study the genomics of vertebrate Evo-Devo. J Exp Zool B Mol Dev Evol. 324:316-41. doi: 10.1002/jez.b.22589.

Postlethwait JH. Wrecks of Ancient Life": Genetic Variants Vetted by Natural Selection. Genetics. 2015 Jul;200(3):675-8. doi: 10.1534/genetics.115.178442.

Gehrke AR, Schneider I, de la Calle-Mustienes E, Tena JJ, Gomez-Marin C, Chandran M, Nakamura T, Braasch I, Postlethwait JH, Gómez-Skarmeta JL, Shubin NH.  (2015) Deep conservation of wrist and digit enhancers in fish.  Proc Natl Acad Sci U S A. 112:803-8

Shin S, Ahn D, Kim S, Pyo C, Lee H, Kim MK, Lee J, Lee J, Detrich H, Postlethwait JH, Edwards D, Lee S, Lee J, Park H.  (2014) The genome sequence of the Antarctic bullhead notothen reveals evolutionary adaptations to a cold environment.  Genome Biol. 15(9):468.

Braasch I, Guiguen Y, Loker R, Letaw JH, Ferrara A, Bobe J, Postlethwait JH. (2014) Connectivity of vertebrate genomes: Paired-related homeobox (Prrx) genes in spotted gar, basal teleosts, and tetrapods. Comp Biochem Physiol C Toxicol Pharmacol. 163:24-36.

Spotted gar (Lepisosteus oculatus), a holostean rayfin fish and one of Darwin’s defining examples of ‘living fossils’, informs the ancestry of vertebrate gene functions and connects vertebrate genomes. The gar and teleost lineages diverged shortly before the teleost genome duplication (TGD), an event with major impacts on the evolution of teleost genomes and gene functions. Evolution after the earlier two vertebrate genome duplication events (VGD1 & VGD2) also complicates the analysis of vertebrate gene family history and the evolution of gene function because lineage-specific genome reshuffling and loss of gene duplicates (ohnologs) can obscure the distinction of orthologs and paralogs across lineages and leads to false conclusions about the origin of vertebrate genes and their functions. We developed a ‘chromonome’ (a chromosome-level genome assembly) for spotted gar. Analysis shows that gar retained many paralogs from VGD1 & VGD2 that were differentially lost in teleosts and lobefins (coelacanth, tetrapods). We further show that spotted gar can be reared as a laboratory model enabling the functional testing of hypotheses aboutthe origin of rayfin and lobefin gene activities without the confounding effects of the TGD. The spotted gar genome sequence also helps identify cis-regulatory elements conserved between teleosts and tetrapods, thereby revealing hidden orthology among regulatory elements that cannot be established by direct teleost-tetrapod comparisons. Using whole genome alignments of teleosts, spotted gar, coelacanth, and tetrapods, we identify conserved non-coding elements (CNEs) that were gained and lost after various key nodes of vertebrate evolution. This information enables us to study on a genome-wide scale the role of regulatory sub- and neo-functionalization after the TGD and helps infer targets of cis-regulatory elements that we test in vivo using transgenic reporter assays. This living fossil helps define ancestral pre-TGD gene functions and links teleost genomes to human biology in health and disease.

Sala Conferenze
venerdì 18 dicembre 2015 - ore 12.00

Per Informazioni:
Filomena Ristoratore
Sezione di Ricerca Scientifica
Biologia ed Evoluzione Organismi Marini
Stazione Zoologica Anton Dohrn
tel. 081 5833251
e-mail: filomena.ristoratore(at)szn.it

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