Teleost fish provide important models for understanding human health and disease. These include models for cancer and tumorigenesis, human development and infant health, cardiovascular disease, eye disease, bone disease, environmental toxicology, ageing, and genome structure and regulation. Because teleost fish share a history of genome expansion, likely due to genome duplication, they often have two copies of single copy human genes. The partitioning of ancestral gene subfunctions between duplicated teleost gene copies facilitates analysis of ancestral gene functions shared with humans. The long-term objective of the proposed work is to provide resources related to duplicated teleost genes to greatly expand the utility of existing teleost models for human development, organ function, health, and disease.
Aim 1 is to develop TelGen, software resources to automate the identification and phylogenetic analysis of duplicated genes in the sequenced genomes of teleost fish.
Aim 2 is to use the new software to identify, investigate, and make publicly accessible in the TelGen2 database, the set of gene duplicates that arose in the proposed ray-fin genome duplication event.
Aim 3 is to identify the most recently diverging, pre-duplication ray-fin lineage, and make available tangible genomic resources, including large insert genomic clones and cDNA libraries, and OldFish, a database for these sequences. Finally, Aim 4 is to create TelExDB, a resource of gene expression data for both copies of teleost duplicates of human disease genes, and to investigate general principles for the evolution of function in teleost gene duplicates. These resources and studies will improve connectivities and utility of teleost models by providing a general understanding of duplicate gene divergence across teleosts. In addition, they facilitate analysis in cases where the early essential function of a single copy mammalian gene obscures a later function. Analysis of duplicated teleost genes can ease discoveryof candidate tissue-specific regulatory elements and protein structural motifs that may be targets for drugs withfewer side effects.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
3R01RR020833-04S1
Application #
7909156
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Chang, Michael
Project Start
2009-09-04
Project End
2010-09-03
Budget Start
2009-09-04
Budget End
2010-09-03
Support Year
4
Fiscal Year
2009
Total Cost
$219,967
Indirect Cost
Name
University of Oregon
Department
Other Basic Sciences
Type
Organized Research Units
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
Pasquier, Jeremy; Braasch, Ingo; Batzel, Peter et al. (2017) Evolution of gene expression after whole-genome duplication: New insights from the spotted gar genome. J Exp Zool B Mol Dev Evol 328:709-721
Cal, Laura; MegÍas, Manuel; Cerdá-Reverter, José Miguel et al. (2017) BAC Recombineering of the Agouti Loci from Spotted Gar and Zebrafish Reveals the Evolutionary Ancestry of Dorsal-Ventral Pigment Asymmetry in Fish. J Exp Zool B Mol Dev Evol 328:697-708
Sullivan, Con; Lage, Christopher R; Yoder, Jeffrey A et al. (2017) Evolutionary divergence of the vertebrate TNFAIP8 gene family: Applying the spotted gar orthology bridge to understand ohnolog loss in teleosts. PLoS One 12:e0179517
Suarez-Bregua, Paula; Torres-Nuñez, Eva; Saxena, Ankur et al. (2017) Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathway. FASEB J 31:569-583
Postlethwait, John H; Yan, Yi-Lin; Desvignes, Thomas et al. (2016) Embryogenesis and early skeletogenesis in the antarctic bullhead notothen, Notothenia coriiceps. Dev Dyn 245:1066-1080
Braasch, Ingo; Gehrke, Andrew R; Smith, Jeramiah J et al. (2016) The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons. Nat Genet 48:427-37
Gehrke, Andrew R; Schneider, Igor; de la Calle-Mustienes, Elisa et al. (2015) Deep conservation of wrist and digit enhancers in fish. Proc Natl Acad Sci U S A 112:803-8
McCluskey, Braedan M; Postlethwait, John H (2015) Phylogeny of zebrafish, a ""model species,"" within Danio, a ""model genus"". Mol Biol Evol 32:635-52
Braasch, Ingo; Peterson, Samuel M; Desvignes, Thomas et al. (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
Desvignes, T; Batzel, P; Berezikov, E et al. (2015) miRNA Nomenclature: A View Incorporating Genetic Origins, Biosynthetic Pathways, and Sequence Variants. Trends Genet 31:613-626

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