EVOLUTION OF IMMUNE RECOGNITION AND EVASION

Summary

Principal Investigator: Austin Hughes
Abstract: DESCRIPTION (provided by applicant): The vertebrate immune system includes numerous proteins involved in the recognition and elimination of parasitic organisms. In vertebrates, the most important system for eliminating intracellular parasites (such as viruses) involves presentation of parasite-derived peptides by class I major histocompatibility complex (MHC) molecules to cytotoxic T cells (CD8+TL). The general goals of this research are to understand the origin and evolution of key molecular components of the vertebrate immune system and to understand the evolution of molecular adaptations in parasitic organisms that evade recognition and elimination by the host's immune system. The methods used in this research involve statistical analysis of published DNA sequence data, of which a large amount is now available both for immune system genes and for genes of major human pathogens (particularly viruses). The purposes of these analyses are as follows: (1) to test the hypothesis that the recognition systems of vertebrate immunity have given rise to natural selection favoring amino acid sequence diversity in parasite protein regions that are targets for immune recognition, while parasites have correspondingly selection for variation in host immune system molecules;(2) to test the hypothesis that epitopes presented by the host MHC to CD8+TL are subject to conflicting selection pressures, including both selection to evade immune recognition and selection to conserve sequence patterns important for viral fitness;(3) to reconstruct patterns of recombination in the evolution of pathogenic viruses and bacteria;and (4) to use phylogenetic analyses of key immune system families, along with information regarding their expression and interactions, in order to reconstruct the evolutionary process whereby members of multi-gene families playing key roles in the immune system have become functionally differentiated. By increasing our understanding of how genetic variation enables pathogens to evade recognition and elimination by the human immune system, this research will provide basic knowledge useful in designing public health strategies to counteract important human pathogens such as human immunodeficiency virus 1 (HIV-1) and hepatitis C virus. In addition, by increasing our understanding of the population diversity and evolutionary history of human immune system genes, this research will enhance our knowledge of human immune function in health and disease.
Funding Period: ----------------1990 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Accumulation of slightly deleterious mutations in the mitochondrial genome: a hallmark of animal domestication
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Gene 515:28-33. 2013
  2. pmc Near neutrality: leading edge of the neutral theory of molecular evolution
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, South Carolina 29208, USA
    Ann N Y Acad Sci 1133:162-79. 2008
  3. pmc MHC class I characterization of Indonesian cynomolgus macaques
    Chad J Pendley
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53706, USA
    Immunogenetics 60:339-51. 2008
  4. pmc Genome-wide SNP typing reveals signatures of population history
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Genomics 92:1-8. 2008
  5. pmc Polymorphism at the apical membrane antigen 1 locus reflects the world population history of Plasmodium vivax
    Priscila Grynberg
    Departamento de Parasitologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Av Antonio Carlos 6627, 31270 901 Belo Horizonte, MG, Brazil
    BMC Evol Biol 8:123. 2008
  6. pmc Functional diversification of the toll-like receptor gene family
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Immunogenetics 60:249-56. 2008
  7. pmc Comprehensive immunological evaluation reveals surprisingly few differences between elite controller and progressor Mamu-B*17-positive simian immunodeficiency virus-infected rhesus macaques
    Nicholas J Maness
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, Wisconsin 53711, USA
    J Virol 82:5245-54. 2008
  8. pmc Identification of MHC class I sequences in Chinese-origin rhesus macaques
    Julie A Karl
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53706, USA
    Immunogenetics 60:37-46. 2008
  9. pmc Nucleotide sequence polymorphism in circoviruses
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, United States
    Infect Genet Evol 8:130-8. 2008
  10. pmc Alternative splicing, gene duplication and connectivity in the genetic interaction network of the nematode worm Caenorhabditis elegans
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Genetica 134:181-6. 2008

Scientific Experts

  • Austin Hughes
  • A Conley
  • Haiwei Luo
  • Somchai Jongwutiwes
  • Chaturong Putaporntip
  • DAVID H O'CONNOR
  • Benjamin N Bimber
  • Ericka A Becker
  • Shelby L O'Connor
  • Stephanie Jiménez Irausquin
  • Roger W Wiseman
  • Julie A Karl
  • Robert Friedman
  • Nancy A Wilson
  • Thomas C Friedrich
  • Benjamin J Burwitz
  • David I Watkins
  • Alex J Blasky
  • Nicholas J Maness
  • Helen Piontkivska
  • Michael Lauck
  • Benoit Callendret
  • Simon M Lank
  • Enrique J León
  • Kevin J Campbell
  • David A Price
  • Emma Gostick
  • Chad J Pendley
  • John T Loffredo
  • Shari M Piaskowski
  • Gemma E May
  • Alessandro Sette
  • John Sidney
  • Philip A Mudd
  • Joseph M Boggs
  • Joana C Silva
  • Dana L Hasselschwert
  • Christopher M Walker
  • Priyasma Bhoumik
  • Michael J Fuller
  • Ann M Detmer
  • Gennadiy I Bondarenko
  • Esper G Kallas
  • Priscila Grynberg
  • Taeko Soma
  • Jessica Furlott
  • C J Corbin
  • Ryan S Schwarz
  • Kristi M Westover
  • Anne Averdam
  • I I Slukvin
  • Anindita Chakrabarty
  • João R Rebello Pinho
  • Saravanan Rajabojan
  • April H South
  • Flair J Carrilho
  • Adam J Ericsen
  • Rob Striker
  • Mónica V Alvarado-Mora
  • Dipankar Bhattacharya
  • Charles M Burns
  • Heather B Eccleston
  • James B Munro
  • Jane M Carlton
  • Jens Bukh
  • Robert H Purcell
  • Ryan Heksch
  • Amy Egan
  • Mark Maffitt
  • Caitlin E MacNair
  • Jennifer J Lhost
  • Katherine J Campbell
  • Edward T Mee
  • Nicola J Rose
  • Randall C Johnson
  • Toshifumi Gushima
  • Jennifer J Tuscher
  • Emily N Chin
  • Ronald C Desrosiers
  • David G Bowen
  • Leandro F Tarosso
  • Justin M Greene
  • Sabri Sanabani
  • Dawn M Dudley
  • Mary Carrington
  • James M Sosman
  • Naglaa H Shoukry
  • Jason S Reed
  • Nicholas C Caruccio
  • Haiying L Grunenwald

Detail Information

Publications93

  1. pmc Accumulation of slightly deleterious mutations in the mitochondrial genome: a hallmark of animal domestication
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Gene 515:28-33. 2013
    ....
  2. pmc Near neutrality: leading edge of the neutral theory of molecular evolution
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, South Carolina 29208, USA
    Ann N Y Acad Sci 1133:162-79. 2008
    ..Slightly deleterious variants are a transient feature of evolution in the long term, but they have substantially affected contemporary species, including our own...
  3. pmc MHC class I characterization of Indonesian cynomolgus macaques
    Chad J Pendley
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53706, USA
    Immunogenetics 60:339-51. 2008
    ....
  4. pmc Genome-wide SNP typing reveals signatures of population history
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Genomics 92:1-8. 2008
    ....
  5. pmc Polymorphism at the apical membrane antigen 1 locus reflects the world population history of Plasmodium vivax
    Priscila Grynberg
    Departamento de Parasitologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Av Antonio Carlos 6627, 31270 901 Belo Horizonte, MG, Brazil
    BMC Evol Biol 8:123. 2008
    ..In particular, we tested for a signature of the introduction of P. vivax into the New World at the time of the European conquest and African slave trade and subsequent population expansion...
  6. pmc Functional diversification of the toll-like receptor gene family
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Immunogenetics 60:249-56. 2008
    ..Thus, the vertebrate TLRs provide an example of a multi-gene family in which gene duplication has been followed by extensive changes in certain aspects of gene function, while others have been conserved throughout vertebrate history...
  7. pmc Comprehensive immunological evaluation reveals surprisingly few differences between elite controller and progressor Mamu-B*17-positive simian immunodeficiency virus-infected rhesus macaques
    Nicholas J Maness
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, Wisconsin 53711, USA
    J Virol 82:5245-54. 2008
    ..Most importantly, our data indicate that the important differences between Mamu-B*17-positive ECs and progressors are not readily discernible using standard assays to measure immune responses...
  8. pmc Identification of MHC class I sequences in Chinese-origin rhesus macaques
    Julie A Karl
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53706, USA
    Immunogenetics 60:37-46. 2008
    ..The discovery of 27 novel MHC class I sequences in this analysis underscores the genetic diversity of Chinese rhesus macaques and contributes reagents that will be valuable for studying cellular immunology in this population...
  9. pmc Nucleotide sequence polymorphism in circoviruses
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, United States
    Infect Genet Evol 8:130-8. 2008
    ..Such a population history is consistent with the epidemiological evidence of a recent worldwide spread of PCV2...
  10. pmc Alternative splicing, gene duplication and connectivity in the genetic interaction network of the nematode worm Caenorhabditis elegans
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Genetica 134:181-6. 2008
    ..These results support the hypothesis that certain key proteins with high degrees of network connectedness are subject to selection opposing the occurrence of alternatively spliced forms...
  11. pmc CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation
    John T Loffredo
    Wisconsin National Primate Research Center WNPRC, University of Wisconsin Madison, Madison, Wisconsin, United States of America
    PLoS ONE 2:e1152. 2007
    ..SIV replication was rapidly controlled with the reappearance of CD8+ cells, implicating that these cells actively suppress viral replication in ECs...
  12. pmc AIDS virus specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape
    Nicholas J Maness
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Exp Med 204:2505-12. 2007
    ..The discovery of an immunodominant CD8-TL response in elite controller macaques against a cryptic epitope suggests that the AIDS virus-specific cellular immune response is likely far more complex than is generally assumed...
  13. pmc Codon-based tests of positive selection, branch lengths, and the evolution of mammalian immune system genes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Immunogenetics 60:495-506. 2008
    ..Our results showed that b (N)/b (S) was consistently elevated in immune system genes, but neither the search for branches with b (N) > b (S) nor the branch-site method revealed this trend...
  14. pmc Distinctive pattern of sequence polymorphism in the NS3 protein of hepatitis C virus type 1b reflects conflicting evolutionary pressures
    Stephanie Jiménez Irausquin
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    J Gen Virol 89:1921-9. 2008
    ....
  15. pmc SIV genome-wide pyrosequencing provides a comprehensive and unbiased view of variation within and outside CD8 T lymphocyte epitopes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America
    PLoS ONE 7:e47818. 2012
    ....
  16. ncbi Phylogenetic analysis of genome rearrangements among five mammalian orders
    Haiwei Luo
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Mol Phylogenet Evol 65:871-82. 2012
    ..We discussed the influence of rate differences among lineages and other factors that may contribute to different resolutions of mammalian ordinal relationships by different methods of phylogenetic reconstruction...
  17. pmc Phylogenetic analysis supports horizontal gene transfer of L-amino acid oxidase gene in Streptococcus oligofermentans
    Joseph M Boggs
    Department of Biological Sciences, University of South Carolina, 715 Sumter St, Columbia, SC 29208, USA
    Infect Genet Evol 12:1005-9. 2012
    ....
  18. pmc Reduced microsatellite heterozygosity in island endemics supports the role of long-term effective population size in avian microsatellite diversity
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Genetica 138:1271-6. 2010
    ..These results support the hypothesis that long-term effective population size can be an important causative factor behind differences among species with respect to microsatellite heterozygosity...
  19. pmc Low level of sequence diversity at merozoite surface protein-1 locus of Plasmodium ovale curtisi and P. ovale wallikeri from Thai isolates
    Chaturong Putaporntip
    Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
    PLoS ONE 8:e58962. 2013
    ..Although sequence diversity in the MSP-1 locus has been extensively analyzed in field isolates of Plasmodium falciparum and P. vivax, the extent of variation in its homologues in P. ovale curtisi and P. ovale wallikeri, remains unknown...
  20. pmc Gene order phylogeny of the genus Prochlorococcus
    Haiwei Luo
    Department of Biological Sciences, University of South Carolina, Columbia, SC, USA
    PLoS ONE 3:e3837. 2008
    ..This character was used to resolve the evolutionary history within the genus Prochlorococcus, a group of marine cyanobacteria...
  21. pmc Complete characterization of killer Ig-like receptor (KIR) haplotypes in Mauritian cynomolgus macaques: novel insights into nonhuman primate KIR gene content and organization
    Benjamin N Bimber
    Department of Pathology and Laboratory Medicine, Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53706, USA
    J Immunol 181:6301-8. 2008
    ..The findings from this study fundamentally advance our understanding of KIR genetics in nonhuman primates and establish a foundation from which to study KIR signaling in disease pathogenesis...
  22. pmc Differential selective pressures on the merozoite surface protein 2 locus of Plasmodium falciparum in a low endemic area
    Chaturong Putaporntip
    Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
    Gene 427:51-7. 2008
    ..falciparum population in Thailand as a result of effective control measures that have sharply reduced the incidence of malaria infection...
  23. pmc Genome size reduction in the chicken has involved massive loss of ancestral protein-coding genes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, USA
    Mol Biol Evol 25:2681-8. 2008
    ....
  24. pmc The origin of adaptive phenotypes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Proc Natl Acad Sci U S A 105:13193-4. 2008
  25. pmc Synonymous and nonsynonymous polymorphisms versus divergences in bacterial genomes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, USA
    Mol Biol Evol 25:2199-209. 2008
    ....
  26. pmc More effective purifying selection on RNA viruses than in DNA viruses
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29205, USA
    Gene 404:117-25. 2007
    ..The fact that the negative allometry was more pronounced in RNA viruses than in DNA viruses provided additional evidence that purifying selection is more effective in the former than in the latter...
  27. ncbi Rapid evolution of the trophoblast kunitz domain proteins (TKDPs)-a multigene family in ruminant ungulates
    Anindita Chakrabarty
    Department of Veterinary Pathobiology, University of Missouri Columbia, Columbia, Missouri 65211, USA
    J Mol Evol 63:274-82. 2006
    ....
  28. ncbi Evolutionary relationships of vertebrate NACHT domain-containing proteins
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, Columbia, SC 29208, USA
    Immunogenetics 58:785-91. 2006
    ....
  29. ncbi Homologous recombination and the pattern of nucleotide substitution in Ehrlichia ruminantium
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter Street, Columbia, SC 29208, USA
    Gene 387:31-7. 2007
    ....
  30. ncbi Variable intensity of purifying selection on cytotoxic T-lymphocyte epitopes in hepatitis C virus
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Virus Res 123:147-53. 2007
    ....
  31. ncbi Nucleotide usage, synonymous substitution pattern, and past recombination in genomes of Streptococcus pyogenes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29205, USA
    Infect Genet Evol 7:188-96. 2007
    ..On the other hand, nucleotide content, when suitably measured, can form one of a set of biological indicators that can be used to identify candidate genes for horizontal gene transfer...
  32. ncbi Likelihood-ratio tests for positive selection of human and mouse duplicate genes reveal nonconservative and anomalous properties of widely used methods
    Robert Friedman
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Mol Phylogenet Evol 42:388-93. 2007
    ..These results suggested that LRT-based tests for positive selection may be sensitive to certain factors that make it difficult to reconstruct the true pattern of nucleotide substitution...
  33. ncbi Sharing of transcription factors after gene duplication in the yeast Saccharomyces cerevisiae
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg 700 Sumter St, Columbia, SC 29208, USA
    Genetica 129:301-8. 2007
    ..These results suggest that functional differentiation of genes after duplication is a multi-dimensional process, with different duplicate pairs differentiating in different ways...
  34. ncbi Patterns of sequence evolution at epitopes for host antibodies and cytotoxic T-lymphocytes in human immunodeficiency virus type 1
    Helen Piontkivska
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia SC 29208, USA
    Virus Res 116:98-105. 2006
    ..The pattern seen at CTL epitopes may represent the result of conflicting pressures favoring conservation of the amino acid sequence for functional reasons and amino acid replacements for reasons of CTL escape...
  35. ncbi Pattern of gene duplication in the Cotesia congregata Bracovirus
    Robert Friedman
    Bioinformatics Facility, University of Connecticut, Storrs, CT 06269, USA
    Infect Genet Evol 6:315-22. 2006
    ..Phylogenies provided no unequivocal evidence of horizontal gene transfer between the wasp host and the polydnavirus, but in some cases there were suggestions of such gene transfer...
  36. ncbi Cloning of rhesus monkey LILRs
    I I Slukvin
    Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, USA
    Tissue Antigens 67:331-7. 2006
    ..Characterization of rhesus LILRs will facilitate use of this non-human primate model for the study of the functional role(s) of LILRs, including immune regulation through interaction with non-classical MHC class I molecules...
  37. ncbi Across-tissue expression and evolution of genes controlled by the Aire transcription factor
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Genomics 88:462-7. 2006
    ..Thus the set of Aire-activated genes is subject to change over evolutionary time and includes genes of recent origin...
  38. ncbi Nucleotide substitution at the highly polymorphic K1 locus of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus)
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, United States
    Infect Genet Evol 7:110-5. 2007
    ....
  39. ncbi Contrasting patterns of transcript abundance in tumour tissue and cancer cell lines
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208, USA
    Appl Bioinformatics 5:201-10. 2006
    ..These results imply that data on gene expression in cancer cell lines should be used with caution in inferring gene expression of in vivo tumours...
  40. ncbi Evolution of cytotoxic T-lymphocyte epitopes in hepatitis B virus
    Kristi M Westover
    Department of Biology, Winthrop University, Rock Hill, SC 29733, USA
    Infect Genet Evol 7:254-62. 2007
    ..The results support the hypothesis that CTL-driven selection has been an important factor in long-term evolution of HBV...
  41. ncbi Placental expression and molecular characterization of aromatase cytochrome P450 in the spotted hyena (Crocuta crocuta)
    A J Conley
    Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, 1 Shields Avenue, Davis, CA 95616, USA
    Placenta 28:668-75. 2007
    ..Other hyaenids and carnivores must be investigated to determine the morphological and functional ancestral state of their placentas, as it relates to evolutionary relationships among species in this important taxonomic group...
  42. pmc Rapid fixation of a distinctive sequence motif in the 3' noncoding region of the clade of West Nile virus invading North America
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, United States
    Gene 399:152-61. 2007
    ....
  43. ncbi Evolution of suiform aromatases: ancestral duplication with conservation of tissue-specific expression in the collared peccary (Pecari tayassu)
    C J Corbin
    Department of Population Health and Reproduction, University of California, Davis, CA, USA
    J Mol Evol 65:403-12. 2007
    ....
  44. pmc The effect of branch lengths on phylogeny: an empirical study using highly conserved orthologs from mammalian genomes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Building, 700 Sumter Street, Columbia, SC 29208, USA
    Mol Phylogenet Evol 45:81-8. 2007
    ..Thus, in these data, a tendency of long and short branches to cluster together ("opposite-branch attraction") seemed to be more of a problem than long-branch attraction...
  45. pmc Phylogeny and recombination history of gallid herpesvirus 2 (Marek's disease virus) genomes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Virus Res 130:28-33. 2007
    ..The two loci (UL49.5 and RLORF12) that were homogenized among the virulent genomes GA, Md5, and Md11 are candidates for contributing to viral virulence...
  46. ncbi Genomics and diversity of the common marmoset monkey NK complex
    Anne Averdam
    Department of Primate Genetics, German Primate Center, Gottingen, Germany
    J Immunol 178:7151-61. 2007
    ..Alternative transcriptional start sites were found, but these probably do not lead to a change of the translational start site or result in longer or shorter cytoplasmic regions of these type II membrane receptors...
  47. ncbi Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level
    A L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Heredity (Edinb) 99:364-73. 2007
    ..Rather adaptive phenotypes are much more likely to result from other causes, including single amino-acid changes; deletion or silencing of genes or changes in the pattern of gene expression...
  48. ncbi Evolution of the lung surfactant proteins in birds and mammals
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Immunogenetics 59:565-72. 2007
    ..Further, they imply that the loss of surfactant protein genes in the avian lineages formed part of major genomic rearrangement events that involved the loss of other genes as well...
  49. ncbi Coding sequence polymorphism in avian mitochondrial genomes reflects population histories
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter Street, Columbia, SC 29208, USA
    Mol Ecol 16:1369-76. 2007
    ..The reduced genetic diversity of Nearctic migrants provides an additional basis for concern for the survival of these species, which are threatened by loss of habitat in the winter range and by introduced disease...
  50. pmc Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques
    Shelby L O'Connor
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53706, USA
    Immunogenetics 59:449-62. 2007
    ....
  51. ncbi Micro-scale signature of purifying selection in Marburg virus genomes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Gene 392:266-72. 2007
    ..The ability of purifying selection to break up linkage between synonymous and nonsynonymous polymorphisms on such a fine scale has not been reported in any other genome...
  52. ncbi A gene family of putative immune recognition molecules in the hydroid Hydractinia
    Ryan S Schwarz
    Department of Biology, The University of New Mexico, Albuquerque, NM 87131 0001, USA
    Immunogenetics 59:233-46. 2007
    ....
  53. pmc Genome reduction by deletion of paralogs in the marine cyanobacterium Prochlorococcus
    Haiwei Luo
    Department of Biological Sciences, University of South Carolina, SC, USA
    Mol Biol Evol 28:2751-60. 2011
    ....
  54. pmc A survey of schistosome protein domain types: insights into unique biological properties
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Mol Biochem Parasitol 177:100-5. 2011
    ..mansoni suggests that this species may be infected by a virus of this group, which might be useful as a biological control agent...
  55. pmc Conflicting selection pressures on T-cell epitopes in HIV-1 subtype B
    Stephanie Jiménez Irausquin
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Building, 700 Sumter St, Columbia, SC 29208, USA
    Infect Genet Evol 11:483-8. 2011
    ....
  56. pmc Genome sequences reveal divergence times of malaria parasite lineages
    Joana C Silva
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Parasitology 138:1737-49. 2011
    ..knowlesi are now available, together with the draft genomes of the chimpanzee parasite P. reichenowi, three rodent parasites, P. yoelii yoelli, P. berghei and P. chabaudi chabaudi, and one avian parasite, P. gallinaceum...
  57. pmc Ongoing purifying selection on intergenic spacers in group A streptococcus
    Haiwei Luo
    Department of Biological Sciences, University of South Carolina, Columbia, 700 Sumter St, SC 29208, USA
    Infect Genet Evol 11:343-8. 2011
    ....
  58. pmc Runaway evolution of the male-specific exon of the doublesex gene in Diptera
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, 29205, USA
    Gene 472:1-6. 2011
    ....
  59. ncbi Recombinational histories of avian infectious bronchitis virus and turkey coronavirus
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Arch Virol 156:1823-9. 2011
    ..The latter hypothesis was supported by a phylogeny of S proteins from representative coronaviruses, in which S proteins of AIBV and TCoV fell in the same clade...
  60. pmc Evolutionary diversification of the avian fatty acid-binding proteins
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Gene 490:1-5. 2011
    ....
  61. pmc Evolution of adaptive phenotypic traits without positive Darwinian selection
    A L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Heredity (Edinb) 108:347-53. 2012
    ..The PRM mechanism can easily explain cases of explosive adaptive radiation, as well as recently reported cases of apparent adaptive evolution over ecological time...
  62. pmc Distinctive amino acid composition profiles in salivary proteins of the tick Ixodes scapularis
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Ticks Tick Borne Dis 2:219-24. 2011
    ..scapularis sialome include at least some apparently antigenic proteins that might be tested experimentally to determine whether they would be suitable candidates for anti-tick vaccines...
  63. pmc Analysis of hepatitis C virus intrahost diversity across the coding region by ultradeep pyrosequencing
    Michael Lauck
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA
    J Virol 86:3952-60. 2012
    ..The approach described here is broadly applicable to studies of viral diversity and could help to improve the efficacy of direct-acting antiviral agents (DAA) in the treatment of HCV-infected patients...
  64. pmc Amino acid sequence coevolution in the insect bursicon ligand-receptor system
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29205, USA
    Mol Phylogenet Evol 63:617-24. 2012
    ....
  65. pmc Escape from CD8(+) T cell responses in Mamu-B*00801(+) macaques differentiates progressors from elite controllers
    Philip A Mudd
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53711, USA
    J Immunol 188:3364-70. 2012
    ..By contrast, virus in elite controller macaques showed little evidence of variation in epitopes recognized by immunodominant CD8(+) T lymphocytes, implying that these cells play a role in viral control...
  66. pmc Experimental analysis of sources of error in evolutionary studies based on Roche/454 pyrosequencing of viral genomes
    Ericka A Becker
    Wisconsin National Primate Research Center, University of Wisconsin, WI, USA
    Genome Biol Evol 4:457-65. 2012
    ..On the other hand, if the goal is to estimate nucleotide diversity, an optimal strategy might be to include all observed variants (even those at less than 1% frequency), while masking out homopolymer runs of four or more nucleotides...
  67. pmc Reassortment of ancient neuraminidase and recent hemagglutinin in pandemic (H1N1) 2009 virus
    Priyasma Bhoumik
    University of South Carolina, Columbia, South Carolina 29208, USA
    Emerg Infect Dis 16:1748-50. 2010
    ..This pattern implies reassortment and suggests that the novel form of hemagglutinin conferred a selective advantage...
  68. pmc Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8⁺ T cells in early viral evolution
    Benoit Callendret
    Center for Vaccines and Immunity, The Research Institute at Nationwide Children s Hospital, Research II Building, Room WA4104, 700 Children s Drive, Columbus, OH 43205, USA
    J Virol 85:11833-45. 2011
    ..This influence of immune pressure on viral evolution appears to subside as chronic infection is established and genetic drift becomes the dominant evolutionary force...
  69. pmc Origin and diversification of the L-amino oxidase family in innate immune defenses of animals
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, 700 Sumter Street, Columbia, SC 29208, USA
    Immunogenetics 62:753-9. 2010
    ..It is certain such unique features may be functionally important, especially three unique amino acid replacements in close proximity to the putative active site...
  70. pmc Whole-genome characterization of human and simian immunodeficiency virus intrahost diversity by ultradeep pyrosequencing
    Benjamin N Bimber
    University of Wisconsin Madison, Madison, WI 53711, USA
    J Virol 84:12087-92. 2010
    ..While this work applies pyrosequencing to immunodeficiency viruses, this approach could be applied to virtually any viral pathogen...
  71. pmc A phylogenetic approach to gene expression data: evidence for the evolutionary origin of mammalian leukocyte phenotypes
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Evol Dev 11:382-90. 2009
    ....
  72. pmc Gene order phylogeny and the evolution of methanogens
    Haiwei Luo
    Department of Biological Sciences, University of South Carolina, Columbia, SC, USA
    PLoS ONE 4:e6069. 2009
    ..This study suggests a new classification scheme for methanogens. In addition, it indicates that gene order phylogeny can complement traditional sequence-based methods in addressing taxonomic questions for deep relationships...
  73. pmc Ultradeep pyrosequencing detects complex patterns of CD8+ T-lymphocyte escape in simian immunodeficiency virus-infected macaques
    Benjamin N Bimber
    Wisconsin National Primate Research Center, University of Wisconsin Madison, 53706, USA
    J Virol 83:8247-53. 2009
    ..These data demonstrate that pyrosequencing can be used to study the evolution of CD8-TL escape during immunodeficiency virus infection with an unprecedented degree of sensitivity...
  74. pmc Characterization of cynomolgus and vervet monkey placental MHC class I expression: diversity of the nonhuman primate AG locus
    Gennadiy I Bondarenko
    Wisconsin National Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, WI 53715 1299, USA
    Immunogenetics 61:431-42. 2009
    ....
  75. pmc Natural selection maintains a stable polymorphism at the circumsporozoite protein locus of Plasmodium falciparum in a low endemic area
    Chaturong Putaporntip
    Department of Parasitology, Faculty of Medicine, Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Chulalongkorn University, Bangkok, Thailand
    Infect Genet Evol 9:567-73. 2009
    ....
  76. pmc Relaxation of purifying selection on the SAD lineage of live attenuated oral vaccines for rabies virus
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, United States
    Infect Genet Evol 9:827-31. 2009
    ..Understanding the biological effects of the unique mutations accumulated in the vaccine lineage is important because of their potential effects on antigenicity and effectiveness of the vaccine...
  77. pmc More radical amino acid replacements in primates than in rodents: support for the evolutionary role of effective population size
    Austin L Hughes
    Department of Biological Sciences, Coker Life Sciences Building, 715 Sumter St, University of South Carolina, Columbia SC 29208, USA
    Gene 440:50-6. 2009
    ....
  78. pmc Relaxation of purifying selection on live attenuated vaccine strains of the family Paramyxoviridae
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Vaccine 27:1685-90. 2009
    ....
  79. pmc Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques
    Kevin J Campbell
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53706, USA
    Immunogenetics 61:177-87. 2009
    ..These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols...
  80. pmc Nucleotide sequence polymorphism at the apical membrane antigen-1 locus reveals population history of Plasmodium vivax in Thailand
    Chaturong Putaporntip
    Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
    Infect Genet Evol 9:1295-300. 2009
    ..The South, which had by far the lowest sequence diversity of the three regions, showed signs of a population that has expanded from a small number of founders after a bottleneck...
  81. pmc Small effective population sizes and rare nonsynonymous variants in potyviruses
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 715 Sumter St, Columbia SC 29208, USA
    Virology 393:127-34. 2009
    ....
  82. pmc The evolutionary biology of poxviruses
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Infect Genet Evol 10:50-9. 2010
    ....
  83. ncbi Reduced variance of gene expression at numerous loci in a population of chickens selected for high feather pecking
    A L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia 29208, USA
    Poult Sci 89:1858-69. 2010
    ....
  84. pmc Evolutionary conservation of amino acid composition in paralogous insect vitellogenins
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Coker Life Sciences Bldg, 700 Sumter St, Columbia, SC 29208, USA
    Gene 467:35-40. 2010
    ....
  85. pmc Ecology of malaria parasites infecting Southeast Asian macaques: evidence from cytochrome b sequences
    Chaturong Putaporntip
    Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
    Mol Ecol 19:3466-76. 2010
    ..Parasite taxa differed with respect to both the frequency of between-host movement and their frequency of coinfection...
  86. pmc Malaria parasite sequences from chimpanzee support the co-speciation hypothesis for the origin of virulent human malaria (Plasmodium falciparum)
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Mol Phylogenet Evol 57:135-43. 2010
    ..falciparum mitochondrial genomes. The available data are thus most consistent with the hypothesis that P. reichenowi (in the strict sense) and P. falciparum co-speciated with their hosts about 5-7 million years ago...
  87. pmc MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques
    Shelby L O'Connor
    Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA
    Sci Transl Med 2:22ra18. 2010
    ....
  88. pmc Bottleneck effects on vaccine-candidate antigen diversity of malaria parasites in Thailand
    Somchai Jongwutiwes
    Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
    Vaccine 28:3112-7. 2010
    ....
  89. pmc Dynamics of haplotype frequency change in a CD8+TL epitope of simian immunodeficiency virus
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Infect Genet Evol 10:555-60. 2010
    ....
  90. pmc Selection-driven immune escape is not a significant factor in the failure of CD4 T cell responses in persistent hepatitis C virus infection
    Michael J Fuller
    Center for Vaccines and Immunity, The Research Institute at Nationwide Children s Hospital, Columbus, OH 43205, USA
    Hepatology 51:378-87. 2010
    ..The frequency of changes in class II epitopes was not different from flanking regions, so CD4 T cells rarely exert selection pressure against the HCV genome...
  91. pmc Conflicting selection pressures target the NS3 protein in hepatitis C virus genotypes 1a and 1b
    Stephanie Jiménez Irausquin
    Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
    Virus Res 147:202-7. 2010
    ..This pattern was more pronounced in HCV-1b than in HCV-1a, suggesting that there may be differences between the two genotypes with respect to NS3's interaction with host immune recognition...
  92. pmc Adaptive evolution of mammalian aromatases: lessons from Suiformes
    A J Conley
    Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
    J Exp Zool A Ecol Genet Physiol 311:346-57. 2009
    ....