Life Sciences Commons^™

Sequences, Annotation And Single Nucleotide Polymorphism Of The Major Histocompatibility Complex In The Domestic Cat, Naoya Yuhki, James C. Mullikin, Thomas W. Beck, Robert M. Stephens, Stephen J. O'Brien

Biology Faculty Articles

Two sequences of major histocompatibility complex (MHC) regions in the domestic cat, 2.976 and 0.362 Mbps, which were separated by an ancient chromosome break (55–80 MYA) and followed by a chromosomal inversion were annotated in detail. Gene annotation of this MHC was completed and identified 183 possible coding regions, 147 human homologues, possible functional genes and 36 pseudo/unidentified genes) by GENSCAN and BLASTN, BLASTP RepeatMasker programs. The first region spans 2.976 Mbp sequence, which encodes six classical class II antigens (three DRA and three DRB antigens) lacking the functional DP, DQ regions, nine antigen processing molecules (DOA/DOB, DMA/DMB, TAPASIN, and …

Functions, Structure, And Read-Through Alternative Splicing Of Feline Apobec3 Genes, Carsten Munk, Thomas W. Beck, Jorg Zielonka, Agnes Hotz-Wagenblatt, Sarah Chareza, Marion Battenberg, Jens Thielebein, Klaus Cichutek, Ignacio G. Bravo, Stephen J. O'Brien, Martin Lochelt, Naoya Yuhki

Biology Faculty Articles

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 …

The Adaptive Evolution Of The Mammalian Mitochondrial Genome, Rute R. Da Fonseca, Warren E. Johnson, Stephen J. O'Brien, Maria J. Ramos, Agostinho Antunes

Biology Faculty Articles

Background

The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures.

Results

Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome b in species with more-specialized metabolic requirements (such as adaptation to …

Initial Sequence And Comparative Analysis Of The Cat Genome, J. U. Pontius, James C. Mullikin, Douglas R. Smith, Agencourt Bioscience Corporation, Kerstin Lindblad-Toh, Sante Gnerre, Michele Clamp, Jean Chang, R. Stephens, Beena A. Neelam, Natalia Volfovsky, Alejandro A. Schaffer, R. Agarwala, Kristina Narfstrom, William J. Murphy, Urs Giger, Alfred L. Roca, Agostinho Antunes, Marilyn Menotti-Raymond, Naoya Yuhki, Jill Pecon-Slattery, Warren E. Johnson, Guillaume Bourque, Glenn Tesler, Nisc Comparative Sequencing Program, Stephen J. O'Brien

Biology Faculty Articles

The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and …

Primate Tnf Promoters Reveal Markers Of Phylogeny And Evolution Of Innate Immunity, Andres Baena, Alan R. Mootnick, James V. Falvo, Alla V. Tsytsykova, Filipa Ligeiro, Ousmane M. Diop, Claudia Brieva, Pascal Gagneux, Stephen J. O'Brien, Oliver A. Ryder, Anne E. Goldfeld

Biology Faculty Articles

Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry.

Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, …

Clouded Leopard Phylogeny Revisited: Support For Species Recognition And Population Division Between Borneo And Sumatra, Andreas Wilting, Valerie A. Buckley-Beason, Heike Feldhaar, Jurgen Gadau, Stephen J. O'Brien, K. Eduard Linsenmair

Biology Faculty Articles

Background

The clouded leopard (Neofelis nebulosa) is one of the least known cat species and depletion of their forested habitats puts it under heavy pressure. Recently reclassification of Bornean clouded leopards (N. nebulosa diardi) to species level (N.diardi) was suggested based on molecular and morphological evidence. Since the genetic results were based solely on three Bornean samples we re-evaluated this partition using additional samples of Bornean clouded leopards (N = 7) and we were also able to include specimens from Sumatra (N = 3), which were lacking in previous analysis.

Results

We found strong …

An ∼140-Kb Deletion Associated With Feline Spinal Muscular Atrophy Implies An Essential Lix1 Function For Motor Neuron Survival, John C. Fyfe, Marilyn Menotti-Raymond, Victor A. David, Lars Brichta, Alejandro A. Schaffer, R. Agarwala, William J. Murphy, William J. Wedemeyer, Brittany L. Gregory, Bethany G. Buzzell, Meghan C. Drummond, Brunhilde Wirth, Stephen J. O'Brien

Biology Faculty Articles

The leading genetic cause of infant mortality is spinal muscular atrophy (SMA), a clinically and genetically heterogeneous group of disorders. Previously we described a domestic cat model of autosomal recessive, juvenile-onset SMA similar to human SMA type III. Here we report results of a whole-genome scan for linkage in the feline SMA pedigree using recently developed species-specific and comparative mapping resources. We identified a novel SMA gene candidate, LIX1, in an ~140-kb deletion on feline chromosome A1q in a region of conserved synteny to human chromosome 5q15. Though LIX1 function is unknown, the predicted secondary structure is compatible with …

Seroprevalence And Genomic Divergence Of Circulating Strains Of Feline Immunodeficiency Virus Among Felidae And Hyaenidae Species, Jennifer L. Troyer, Jill Pecon-Slattery, Melody E. Roelke, Warren E. Johnson, Sue Vandewoude, Nuria Vazquez-Salat, Meredith Brown, Laurence Frank, Rosie Woodroffe, Christiaan Winterbach, Hanlie Winterbach, Graham Hemson, Mitchell Bush, Kathleen A. Alexander, Eloy Revilla, Stephen J. O'Brien

Biology Faculty Articles

Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. …

Insertional Polymorphisms Of Endogenous Feline Leukemia Viruses, Alfred L. Roca, William G. Nash, Joan C. Menninger, William J. Murphy, Stephen J. O'Brien

Biology Faculty Articles

The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one …

Phylogeography And Genetic Ancestry Of Tigers (Panthera Tigris), Shu-Jin Luo, Jae-Heup Kim, Warren E. Johnson, Joelle Van Der Walt, Janice S. Martenson, Naoya Yuhki, Dale Miquelle, Olga Uphyrkina, John M. Goodrich, Howard Quigley, R. Tilson, Gerald Brady, Paolo Martelli, Vellayan Subramaniam, Charles Mcdougal, Sun Hean, Shi-Qiang Huang, Wenshi Pan, Ullas K. Karanth, Melvin Sunquist, James L. D. Smith, Stephen J. O'Brien

Biology Faculty Articles

Eight traditional subspecies of tiger (Panthera tigris), of which three recently became extinct, are commonly recognized on the basis of geographic isolation and morphological characteristics. To investigate the species' evolutionary history and to establish objective methods for subspecies recognition, voucher specimens of blood, skin, hair, and/or skin biopsies from 134 tigers with verified geographic origins or heritage across the whole distribution range were examined for three molecular markers: (1) 4.0 kb of mitochondrial DNA (mtDNA) sequence; (2) allele variation in the nuclear major histocompatibility complex class II DRB gene; and (3) composite nuclear microsatellite genotypes based on 30 loci. Relatively …

Comparative Genome Organization Of Human, Murine, And Feline Mhc Class Ii Region, Naoya Yuhki, Thomas W. Beck, Robert M. Stephens, Yoko Nishigaki, Kymberly Newmann, Stephen J. O'Brien

Biology Faculty Articles

To study comparative molecular dynamics in the genesis of the major histocompatibility complex (MHC), we determined a complete nucleotide sequence spanning 758,291 bp of the domestic cat (Felis catus) extended and classical class II region. The feline class II MHC includes 44 genes (31 predicted to be expressed) which display DNA sequence homology and ordered gene synteny with human HLA and mouse H2, in extended class II and centromere proximal regions (DM to DO) of the classical class II region. However, remarkable genomic alterations including gene gain and loss plus size differentials of 250 kb are …

Sequencing The Genome Of The Domestic Cat Felis Catus, Stephen J. O'Brien, Eric S. Lander, M. E. Haskins, Urs Giger, Niels C. Pederson, David E. Wildt, William J. Murphy, Naoya Yuhki, Marilyn Menotti-Raymond

Biology Faculty Articles

No abstract provided.

Genomic Microsatellites As Evolutionary Chronometers: A Test In Wild Cats, Carlos A. Driscoll, Marilyn Menotti-Raymond, George Nelson, David Goldstein, Stephen J. O'Brien

Biology Faculty Articles

Nuclear microsatellite loci (2- to 5-bp tandem repeats) would seem to be ideal markers for population genetic monitoring because of their abundant polymorphism, wide dispersal in vertebrate genomes, near selective neutrality, and ease of assessment; however, questions about their mode of generation, mutation rates and ascertainment bias have limited interpretation considerably. We have assessed the patterns of genomic diversity for ninety feline microsatellite loci among previously characterized populations of cheetahs, lions and pumas in recapitulating demographic history. The results imply that the microsatellite diversity measures (heterozygosity, allele reconstitution and microsatellite allele variance) offer proportionate indicators, albeit with large variance, of …

Genetic Evidence For Two Species Of Elephant In Africa, Alfred L. Roca, Nicholas Georgiadis, Jill Pecon-Slattery, Stephen J. O'Brien

Biology Faculty Articles

Elephants from the tropical forests of Africa are morphologically distinct from savannah or bush elephants. Dart-biopsy samples from 195 free-ranging African elephants in 21 populations were examined for DNA sequence variation in four nuclear genes (1732 base pairs). Phylogenetic distinctions between African forest elephant and savannah elephant populations corresponded to 58% of the difference in the same genes between elephant genera Loxodonta (African) and Elephas (Asian). Large genetic distance, multiple genetically fixed nucleotide site differences, morphological and habitat distinctions, and extremely limited hybridization of gene flow between forest and savannah elephants support the recognition and conservation management of two African …

Canine And Feline Parvoviruses Can Use Human Or Feline Transferrin Receptors To Bind, Enter, And Infect Cells, John S. L. Parker, William J. Murphy, Dai Wang, Stephen J. O'Brien, Colin R. Parrish

Biology Faculty Articles

Canine parvovirus (CPV) enters and infects cells by a dynamin-dependent, clathrin-mediated endocytic pathway, and viral capsids colocalize with transferrin in perinuclear vesicles of cells shortly after entry (J. S. L. Parker and C. R. Parrish, J. Virol. 74:1919–1930, 2000). Here we report that CPV and feline panleukopenia virus (FPV), a closely related parvovirus, bind to the human and feline transferrin receptors (TfRs) and use these receptors to enter and infect cells. Capsids did not detectably bind or enter quail QT35 cells or a Chinese hamster ovary (CHO) cell-derived cell line that lacks any TfR (TRVb cells). However, capsids bound and …

A Radiation Hybrid Map Of The Cat Genome: Implications For Comparative Mapping, William J. Murphy, Shan Sun, Zhang-Qun Chen, Naoya Yuhki, Deborah Hirschmann, Marilyn Menotti-Raymond, Stephen J. O'Brien

Biology Faculty Articles

Ordered gene maps of mammalian species are becoming increasingly valued in assigning gene variants to function in human and animal models, as well as recapitulating the natural history of genome organization. To extend this power to the domestic cat, a radiation hybrid (RH) map of the cat was constructed integrating 424 Type I-coding genes with 176 microsatellite markers, providing coverage over all 20 feline chromosomes. Alignment of parallel RH maps of human and cat reveal 100 conserved segments ordered (CSOs) between the species, nearly three times the number observed with reciprocal chromosome painting analyses. The observed number is equivalent to …

A Comparative Gene Map Of The Horse (Equus Caballus), Alexandre R. Caetano, Yow-Ling Shiue, Leslie A. Lyons, Stephen J. O'Brien, Thomas F. Laughlin, Ann T. Bowling, James D. Murray

Biology Faculty Articles

A comparative gene map of the horse genome composed of 127 loci was assembled based on the new assignment of 68 equine type I loci and on data published previously. PCR primers based on consensus gene sequences conserved across mammalian species were used to amplify markers for assigning 68 equine type I loci to 27 horse synteny groups established previously with a horse-mouse somatic cell hybrid panel (SCHP, UC Davis). This increased the number of coding genes mapped to the horse genome by over 2-fold and allowed refinements of the comparative mapping data available for this species. In conjunction with …

Genetic And Phylogenetic Divergence Of Feline Immunodeficiency Virus In The Puma (Puma Concolor), Margaret A. Carpenter, Eric W. Brown, Melanie Culver, Warren E. Johnson, Jill Pecon-Slattery, Dulce Brousset, Stephen J. O'Brien

Biology Faculty Articles

Feline immunodeficiency virus (FIV) is a lentivirus which causes an AIDS-like disease in domestic cats (Felis catus). A number of other felid species, including the puma (Puma concolor), carry a virus closely related to domestic cat FIV. Serological testing revealed the presence of antibodies to FIV in 22% of 434 samples from throughout the geographic range of the puma. FIV-Pco pol gene sequences isolated from pumas revealed extensive sequence diversity, greater than has been documented in the domestic cat. The puma sequences formed two highly divergent groups, analogous to the clades which have been defined for …

Evidence Of Natural Bluetongue Virus Infection Among African Carnivores, Kathleen A. Alexander, N. James Maclachlan, Pieter W. Kat, Carol House, Stephen J. O'Brien, Nicholas W. Lerche, Mary Sawyer, Laurence G. Frank, Kay Holekamp, Laura Smale, J. Weldon Mcnutt, M. Karen Laurenson, M. G. L. Mills, Bennie I. Osburn

Biology Faculty Articles

Bluetongue is an International Office of Epizootics List A disease described as the century's most economically devastating affliction of sheep. Bluetongue (BLU) viruses were thought to infect only ruminants, shrews, and some rodents, but recently, inadvertent administration of BLU virus-contaminated vaccine resulted in mortality and abortion among domestic dogs. We present evidence of natural BLU virus infection among African carnivores that dramatically widens the spectrum of susceptible hosts. We hypothesize that such infection occurred after ingestion of meat and organs from BLU virus infected prey species. The effect of BLU virus on endangered carnivores such as the cheetah and African …

A Lion Lentivirus Related To Feline Immunodeficiency Virus: Epidemiologic And Phylogenetic Aspects, Eric W. Brown, Naoya Yuhki, Craig Packer, Stephen J. O'Brien

Biology Faculty Articles

Feline immunodeficiency virus (FIV) is a novel lentivirus that is genetically homologous and functionally analogous to the human AIDS viruses, human immunodeficiency virus types 1 and 2. FIV causes immunosuppression in domestic cats by destroying the CD4 T-lymphocyte subsets in infected hosts. A serological survey of over 400 free-ranging African and Asian lions (Panthera leo) for antibodies to FIV revealed endemic lentivirus prevalence with an incidence of seropositivity as high as 90%o. A lion lentivirus (FIV-Ple) was isolated by infection of lion lymphocytes in vitro. Seroconversion was documented in two Serengeti lions, and discordance of mother-cub serological status …

Worldwide Prevalence Of Lentivirus Infection In Wild Feline Species: Epidemiologic And Phylogenetic Aspects, Robert A. Olmstead, Raymond Langley, Melody E. Roelke, Robert M. Goeken, Diane Adger-Johnson, Julie P. Goff, John P. Albert, Craig Packer, M. Karen Laurenson, Tim M. Caro, Lue Scheepers, David E. Wildt, Mitchell Bush, Janice S. Martenson, Stephen J. O'Brien

Biology Faculty Articles

The natural occurrence of lentiviruses closely related to feline immunodeficiency virus (FIV) in nondomestic felid species is shown here to be worldwide. Cross-reactive antibodies to FIV were common in several free-ranging populations of large cats, including East African lions and cheetahs of the Serengeti ecosystem and in puma (also called cougar or mountain lion) populations throughout North America. Infectious puma lentivirus (PLV) was isolated from several Florida panthers, a severely endangered relict puma subspecies inhabiting the Big Cypress Swamp and Everglades ecosystems in southern Florida. Phylogenetic analysis of PLV genomic sequences from disparate geographic isolates revealed appreciable divergence from domestic …

Dna Recombination And Natural Selection Pressure Sustain Genetic Sequence Diversity Of The Feline Mhc Class I Genes, Naoya Yuhki, Stephen J. O'Brien

Biology Faculty Articles

Sequence comparisons of seven distinct MHC class I cDNA clones revealed that feline class I molecules have a remarkable similarity to human HLA genes in their organization of functional domains as well as in the nonrandom partitioning of genetic variability according to the functional constraints ascribed to different regions of the MHC molecule. The distribution of the pattern of sequence polymorphism in the cat as compared with genetic diversity of human and mouse class I genes provides evidence for four coordinate factors that contribute to the origin and sustenance of abundant allele diversity that characterizes the MHC in the species. …

Prevalence And Implications Of Feline Coronavirus Infections Of Captive And Free-Ranging Cheetahs (Acinonyx Jubatus), J. L. Heeney, J. F. Evermann, A. J. Mckeirnan, L. Marker-Kraus, M. E. Roelke, M. Bush, D. E. Wildt, D. G. Meltzer, L. Colly, J. Lukas, V. J. Manton, T. Caro, Stephen J. O'Brien

Biology Faculty Articles

The extent and progression of exposure to feline infectious peritonitis (FIP) virus in the cheetah, Acinonyx jubatus, was monitored by a world-wide serological survey with indirect fluorescent antibody titers to coronavirus. The indirect fluorescent antibody assay was validated by Western blots, which showed that all indirect fluorescent antibody-positive cheetah sera detected both domestic cat and cheetah coronavirus structural proteins. There was a poor correlation between indirect fluorescent antibody results and the presence of coronaviruslike particles in cheetah feces, suggesting that electron microscopic detection of shed particles may not be an easily interpreted diagnostic parameter for FIP disease. Low, but …

Genetic Mapping Of Endogenous Rd-114 Retroviral Sequences Of Domestic Cats, Roger H. Reeves, William G. Nash, Stephen J. O'Brien

Biology Faculty Articles

The RD-114 family of endogenous retroviral sequences in domestic cats has been shown to consist of approximately 20 copies of genetically divergent virogenes per haploid genome. The chromosomal localization for four endogenous sequences (RDV1-4) was accomplished by correlating the occurrence of specific feline chromosomes with diagnostic viral DNA fragments in a panel of cat x rodent somatic cell hybrids. Analysis of the hybrid panel revealed that endogenous RD-114 sequences are dispersed on multiple cat chromosomes, that certain proviral segments are polymorphic with respect to the presence or absence of virus, and that a restriction fragment characteristic of inducible RD-114 resides …

Molecular Genetic Characterization Of The Rd-114 Gene Family Of Endogenous Feline Retroviral Sequences, Roger H. Reeves, Stephen J. O'Brien

Biology Faculty Articles

RD-114 is a replication-competent, xenotropic retrovirus which is homologous to a family of moderately repetitive DNA sequences present at ca. 20 copies in the normal cellular genome of domestic cats. To examine the extent and character of genomic divergence of the RD-114 gene family as well as to assess their positional association within the cat genome, we have prepared a series of molecular clones of endogenous RD-114 DNA segments from a genomic library of cat cellular DNA. Their restriction endonuclease maps were compared with each other as well as to that of the prototype-inducible RD-114 which was molecularly cloned from …

Evidence For The Horizontal Acquisition Of Murine Akr Virogenes By Recent Horizontal Infection Of The Germ Line, Stephen J. O'Brien, Janet L. Moore, Malcolm A. Martin, James E. Womack

Biology Faculty Articles

Several recent reports have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV⁺ strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR …

Bvr-1, A Restriction Locus Of A Type C Rna Virus In The Feline Cellular Genome: Pleiotropic Restriction Of Endogenous Balb Virus In Cat X Mouse Somatic Cell Hybrids, Stephen J. O'Brien, Janice M. Simonson

Biology Faculty Articles

Bvr-1 is a dominant X-linked feline gene which restricts the replication of B-tropic murineleukemia virus (B-MuLV) in somatic cell hybrids between murine BALB/c-RAG cells and FL-74 feline cells. Since the hybrids were originally derived by the hypoxanthine aminopterin thymidine selection scheme, counter selection experiments on 6-thioguanine result in preferential survival of hybrid cells which have spontaneously lost the feline X-chromosome on which is located the structural gene for hypoxanthine guanine phosphoribosyl transferase (IMP: pyrophosphate phosphoribosyl transferase, E.C. 2.4.2.8) and Bvr-1. Back selected Bvr-1^- cells express high parental levels of B-MuLV. Bvr-1^- effectively restricts the IdU-mediated induction of …