Genetics and Genomics Commons^™

Adaptive Evolution Of The Matrix Extracellular Phosphoglycoprotein In Mammals, Joao P. Machado, Warren E. Johnson, Stephen J. O'Brien, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

Background

Matrix extracellular phosphoglycoprotein (MEPE) belongs to a family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs) that play a key role in skeleton development, particularly in mineralization, phosphate regulation and osteogenesis. MEPE associated disorders cause various physiological effects, such as loss of bone mass, tumors and disruption of renal function (hypophosphatemia). The study of this developmental gene from an evolutionary perspective could provide valuable insights on the adaptive diversification of morphological phenotypes in vertebrates.

Results

Here we studied the adaptive evolution of the MEPE gene in 26 Eutherian mammals and three birds. The comparative genomic analyses revealed a high degree …

Role Of Exonic Variation In Chemokine Receptor Genes On Aids: Ccrl2 F167y Association With Pneumocystis Pneumonia, Ping An, Rongling Li, Ji Ming Wang, Teizo Yoshimura, Munehisa Takahashi, Ram Samudralal, Stephen J. O'Brien, John Phair, James J. Goedert, Gregory D. Kirk, Jennifer L. Troyer, Efe Sezgin, Susan Buchbinder, Sharyne Donfield, George W. Nelson, Cheryl Winkler

Biology Faculty Articles

Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 andCCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In …

Evolution Of A Major Drug Metabolizing Enzyme Defect In The Domestic Cat And Other Felidae: Phylogenetic Timing And The Role Of Hypercarnivory, Binu Shrestha, J. Michael Reed, Philip T. Starks, Gretchen E. Kaufman, Jared V. Goldstone, Melody E. Roelke, Stephen J. O'Brien, Klaus-Peter Koepfli, Laurence Frank, Michael H. Court

Biology Faculty Articles

The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional …

A Molecular Phylogeny Of Living Primates, Polina L. Perelman, Warren E. Johnson, Christian Roos, Hector Seuanez, Julie E. Horvath, Miguel A. M. Moreira, Bailey Kessing, J. U. Pontius, Melody E. Roelke, Yves Rumpler, Maria P. C. Schneider, Artur Silva, Stephen J. O'Brien, Jill Pecon-Slattery

Biology Faculty Articles

Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate …

Genome-Wide Characterization Of Centromeric Satellites From Multiple Mammalian Genomes, Can Alkan, Maria Francesca Cardone, Claudia Rita Catacchio, Francesca Antonacci, Stephen J. O'Brien, Oliver A. Ryder, Stefania Purgato, Monica Zoli, Evan E. Eichler, Mario Ventura

Biology Faculty Articles

Despite its importance in cell biology and evolution, the centromere has remained the final frontier in genome assembly and annotation due to its complex repeat structure. However, isolation and characterization of the centromeric repeats from newly sequenced species are necessary for a complete understanding of genome evolution and function. In recent years, various genomes have been sequenced, but the characterization of the corresponding centromeric DNA has lagged behind. Here, we present a computational method (RepeatNet) to systematically identify higher-order repeat structures from unassembled whole-genome shotgun sequence and test whether these sequence elements correspond to functional centromeric sequences. We analyzed genome …