Browsing by Subject "Sequence motif analysis"

Now showing 1 - 5 of 5
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    Open Access
    The ancient evolutionary history of polyomaviruses
    (Public Library of Science, 2016) Buck, Christopher B; Van Doorslaer, Koenraad; Peretti, Alberto; Geoghegan, Eileen M; Tisza, Michael J; An, Ping; Katz, Joshua P; Pipas, James M; McBride, Alison A; Camus, Alvin C; McDermott, Alexa J; Dill, Jennifer A; Delwart, Eric; Ng, Terry F F; Farkas, Kata; Austin, Charlotte; Kraberger, Simona; Davison, William; Pastrana, Diana V; Varsani, Arvind
    Author Summary: Polyomaviruses are a family of DNA-based viruses that are known to infect various terrestrial vertebrates, including humans. In this report, we describe our discovery of highly divergent polyomaviruses associated with various marine fish. Searches of public deep sequencing databases unexpectedly revealed the existence of polyomavirus-like sequences in scorpion and spider datasets. Our analysis of these new sequences suggests that polyomaviruses have slowly co-evolved with individual host animal lineages through an established mechanism known as intrahost divergence. The proposed model is similar to the mechanisms through with other DNA viruses, such as papillomaviruses, are thought to have evolved. Our analysis also suggests that distantly related polyomaviruses sometimes recombine to produce new chimeric lineages. We propose a possible taxonomic scheme that can account for these inferred ancient recombination events.
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    Open Access
    Bat accelerated regions identify a bat forelimb specific enhancer in the HoxD locus
    (Public Library of Science, 2016) Booker, Betty M; Friedrich, Tara; Mason, Mandy K; VanderMeer, Julia E; Zhao, Jingjing; Eckalbar, Walter L; Logan, Malcolm; Illing, Nicola; Pollard, Katherine S; Ahituv, Nadav
    Author Summary: The limb is a classic example of vertebrate homology and is represented by a large range of morphological structures such as fins, legs and wings. The evolution of these structures could be driven by alterations in gene regulatory elements that have critical roles during development. To identify elements that may contribute to bat wing development, we characterized sequences that are conserved between vertebrates, but changed significantly in the bat lineage. We then overlapped these sequences with predicted developing limb enhancers as determined by ChIP-seq, finding 166 bat accelerated sequences (BARs). Five BARs that were tested for enhancer activity in mice all drove expression in the limb. Testing the mouse orthologous sequence showed that three had differences in their limb enhancer activity as compared to the bat sequence. Of these, BAR116 was of particular interest as it is located near the HoxD locus, an essential gene complex required for proper spatiotemporal patterning of the developing limb. The bat BAR116 sequence drove robust forelimb expression but the mouse BAR116 sequence did not show enhancer activity. These experiments correspond to analyses of HoxD gene expressions in developing bat limbs, which had strong forelimb versus weak hindlimb expression for Hoxd10 - 11 . Combined, our studies highlight specific genomic regions that could be important in shaping the morphological differences that led to the development of the bat wing.
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    Open Access
    HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC
    (Public Library of Science, 2009) Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F; McMichael, Andrew
    Author Summary HIV is a rapidly evolving virus, displaying enormous genetic diversity between and even within infected individuals, with implications for vaccine design and drug treatment. Yet, recent research has shown that most new infections result from transmission of a single virus resulting in a homogeneous viral population in early infection. The process of diversification from the transmitted virus provides information about the selection pressures experienced by the virus during the establishment of a new infection. In this paper, we studied early diversification of the envelope gene in a cohort of 81 subjects acutely infected with HIV-1 subtype B and found evidence of adaptive evolution, with a proportion of sites that tended to diversify more rapidly than expected under a model of neutral evolution. Several of these rapidly diversifying sites facilitate escape from early cytotoxic immune responses. Interestingly, hypermutation of the virus, brought about by host proteins as a strategy to restrict infection, appeared to be associated with early immune escape. In addition to single base substitutions, insertions and deletions are an important aspect of HIV evolution. We show that insertion and deletion mutations occur evenly across the gene, but are preferentially fixed in the variable loop regions.
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    Open Access
    Identification of a collagen type I adhesin of Bacteroides fragilis
    (Public Library of Science, 2014) Galvão, Bruna P G V; Weber, Brandon W; Rafudeen, Mohamed S; Ferreira, Eliane O; Patrick, Sheila; Abratt, Valerie R
    Bacteroides fragilis is an opportunistic pathogen which can cause life threatening infections in humans and animals. The ability to adhere to components of the extracellular matrix, including collagen, is related to bacterial host colonisation. Collagen Far Western analysis of the B. fragilis outer membrane protein (OMP) fraction revealed the presence two collagen adhesin bands of ∼31 and ∼34 kDa. The collagen adhesins in the OMP fraction were separated and isolated by two-dimensional SDS-PAGE and also purified by collagen affinity chromatography. The collagen binding proteins isolated by both these independent methods were subjected to tandem mass spectroscopy for peptide identification and matched to a single hypothetical protein encoded by B. fragilis NCTC 9343 (BF0586), conserved in YCH46 (BF0662) and 638R (BF0633) and which is designated in this study as cbp1 (collagen binding protein). Functionality of the protein was confirmed by targeted insertional mutagenesis of the cbp1 gene in B. fragilis GSH18 which resulted in the specific loss of both the ∼31 kDa and the ∼34 kDa adhesin bands. Purified his-tagged Cbp1, expressed in a B. fragilis wild-type and a glycosylation deficient mutant, confirmed that the cbp1 gene encoded the observed collagen adhesin, and showed that the 34 kDa band represents a glycosylated version of the ∼31 kDa protein. Glycosylation did not appear to be required for binding collagen. This study is the first to report the presence of collagen type I adhesin proteins in B. fragilis and to functionally identify a gene encoding a collagen binding protein.
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    Open Access
    A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates
    (Public Library of Science, 2013) Park, Cho Rong; Moon, Mi Jin; Park, Sumi; Kim, Dong-Kyu; Cho, Eun Bee; Millar, Robert Peter; Hwang, Jong-Ik; Seong, Jae Young
    The glucagon (GCG) peptide family consists of GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from a common GCG precursor, and the glucose-dependent insulinotropic polypeptide (GIP). These peptides interact with cognate receptors, GCGR, GLP1R, GLP2R, and GIPR, which belong to the secretin-like G protein-coupled receptor (GPCR) family. We used bioinformatics to identify genes encoding a novel GCG-related peptide (GCRP) and its cognate receptor, GCRPR. The GCRP and GCRPR genes were found in representative tetrapod taxa such as anole lizard, chicken, and Xenopus , and in teleosts including medaka, fugu, tetraodon, and stickleback. However, they were not present in mammals and zebrafish. Phylogenetic and genome synteny analyses showed that GCRP emerged through two rounds of whole genome duplication (2R) during early vertebrate evolution. GCRPR appears to have arisen by local tandem gene duplications from a common ancestor of GCRPR , GCGR , and GLP2R after 2R. Biochemical ligand-receptor interaction analyses revealed that GCRP had the highest affinity for GCRPR in comparison to other GCGR family members. Stimulation of chicken, Xenopus , and medaka GCRPRs activated Gα s -mediated signaling. In contrast to chicken and Xenopus GCRPRs, medaka GCRPR also induced Gα q/11 -mediated signaling. Chimeric peptides and receptors showed that the K 16 M 17 K 18 and G 16 Q 17 A 18 motifs in GCRP and GLP1, respectively, may at least in part contribute to specific recognition of their cognate receptors through interaction with the receptor core domain. In conclusion, we present novel data demonstrating that GCRP and GCRPR evolved through gene/genome duplications followed by specific modifications that conferred selective recognition to this ligand-receptor pair.