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      Functions, structure, and read-through alternative splicing of feline APOBEC3 genes

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          Abstract

          APOBEC3 (A3, Apolipoprotein B mRNA-editing catalytic polypeptide 3) genes in the genome of domestic cat (Felis catus) were identified and characterized

          Abstract

          Background

          Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene.

          Results

          Here we identified and characterized several A3 genes in the genome of domestic cat ( Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three very similar A3C genes (a-c), probably generated after two consecutive gene duplications. In addition to these four one-domain A3 proteins, a fifth A3, designated A3CH, is expressed by read-through alternative splicing. Specific feline A3 proteins selectively inactivated only defined genera of feline retroviruses: Bet-deficient feline foamy virus was mainly inactivated by feA3Ca, feA3Cb, and feA3Cc, while feA3H and feA3CH were only weakly active. The infectivity of Vif-deficient feline immunodeficiency virus and feline leukemia virus was reduced only by feA3H and feA3CH, but not by any of the feA3Cs. Within Felidae, A3C sequences show significant adaptive selection, but unexpectedly, the A3H sequences present more sites that are under purifying selection.

          Conclusion

          Our data support a complex evolutionary history of expansion, divergence, selection and individual extinction of antiviral A3 genes that parallels the early evolution of Placentalia, becoming more intricate in taxa in which the arms race between host and retroviruses is harsher.

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          Most cited references55

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          Consed: a graphical tool for sequence finishing.

          Sequencing of large clones or small genomes is generally done by the shotgun approach (Anderson et al. 1982). This has two phases: (1) a shotgun phase in which a number of reads are generated from random subclones and assembled into contigs, followed by (2) a directed, or finishing phase in which the assembly is inspected for correctness and for various kinds of data anomalies (such as contaminant reads, unremoved vector sequence, and chimeric or deleted reads), additional data are collected to close gaps and resolve low quality regions, and editing is performed to correct assembly or base-calling errors. Finishing is currently a bottleneck in large-scale sequencing efforts, and throughput gains will depend both on reducing the need for human intervention and making it as efficient as possible. We have developed a finishing tool, consed, which attempts to implement these principles. A distinguishing feature relative to other programs is the use of error probabilities from our programs phred and phrap as an objective criterion to guide the entire finishing process. More information is available at http:// www.genome.washington.edu/consed/consed. html.
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            The delayed rise of present-day mammals.

            Did the end-Cretaceous mass extinction event, by eliminating non-avian dinosaurs and most of the existing fauna, trigger the evolutionary radiation of present-day mammals? Here we construct, date and analyse a species-level phylogeny of nearly all extant Mammalia to bring a new perspective to this question. Our analyses of how extant lineages accumulated through time show that net per-lineage diversification rates barely changed across the Cretaceous/Tertiary boundary. Instead, these rates spiked significantly with the origins of the currently recognized placental superorders and orders approximately 93 million years ago, before falling and remaining low until accelerating again throughout the Eocene and Oligocene epochs. Our results show that the phylogenetic 'fuses' leading to the explosion of extant placental orders are not only very much longer than suspected previously, but also challenge the hypothesis that the end-Cretaceous mass extinction event had a major, direct influence on the diversification of today's mammals.
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              Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene.

              Several codon-based models for the evolution of protein-coding DNA sequences are developed that account for varying selection intensity among amino acid sites. The "neutral model" assumes two categories of sites at which amino acid replacements are either neutral or deleterious. The "positive-selection model" assumes an additional category of positively selected sites at which nonsynonymous substitutions occur at a higher rate than synonymous ones. This model is also used to identify target sites for positive selection. The models are applied to a data set of the V3 region of the HIV-1 envelope gene, sequenced at different years after the infection of one patient. The results provide strong support for variable selection intensity among amino acid sites The neutral model is rejected in favor of the positive-selection model, indicating the operation of positive selection in the region. Positively selected sites are found in both the V3 region and the flanking regions.
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                Author and article information

                Journal
                Genome Biol
                Genome Biology
                BioMed Central
                1465-6906
                1465-6914
                2008
                3 March 2008
                : 9
                : 3
                : R48
                Affiliations
                [1 ]Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany
                [2 ]SAIC-Frederick, Inc., NCI-Frederick, Laboratory of Genomic Diversity, Frederick, MD 21702-1201, USA
                [3 ]Department of Molecular Biophysics, Research Program Structural and Functional Genomics, German Cancer Research Center, 69120 Heidelberg, Germany
                [4 ]Department of Genome Modifications and Carcinogenesis, Research Program Infection and Cancer, German Cancer Research Center, Heidelberg, Germany
                [5 ]Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany
                [6 ]Institute for Evolution and Biodiversity, Westfälische Wilhems University Münster, 48143 Münster, Germany
                [7 ]Laboratory of Genomic Diversity, NCI at Frederick, Frederick, MD 21702-1201, USA
                Article
                gb-2008-9-3-r48
                10.1186/gb-2008-9-3-r48
                2397500
                18315870
                e6605ad5-94b4-4dab-9526-37b6445828b1
                Copyright © 2008 Münk et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 January 2008
                : 29 February 2008
                : 3 March 2008
                Categories
                Research

                Genetics
                Genetics

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