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Austin L Hughes

Publications and source records attributed to Austin L Hughes.

At least 19 recordsLinked to original sources
PubMed2003

Genome-wide survey for genes horizontally transferred from cellular organisms to baculoviruses.

The phylogeny of 13 viral species in the genera Granulovirus and Nucleopolyhedrovirus (family Baculoviridae) was reconstructed on the basis of 22 conserved protein families shared by all species, and a comprehensive homology search and phylogenetic analysis of the complete genomes of these viruses was used to test for horizontal gene transfer from cellular organisms. Statistically significant evidence of horizontal transfer was found in the case of six protein families (DNA ligase, ribonucleotide reductase 1, SNF2 global transactivator, inhibitor of apoptosis, chitinase, and UDP-glucosyltransferase). Three of these families are known to play key roles in the infection of insect hosts by these viruses. There was evidence that two of these (inhibitor of apoptosis and UDP-glucosyltransferase) were derived from the insect host. By contrast, the gene encoding chitinase in these viruses was evidently derived from a group of bacteria (the gamma subdivision of proteobacteria), which use chitinase to break down fungal chitins.

Animals↗
PubMed2003

Phylogeny of Trypanosomatidae and Bodonidae (Kinetoplastida) based on 18S rRNA: evidence for paraphyly of Trypanosoma and six other genera.

Phylogenetic analysis of 18S rRNA sequences from the families Trypanosomatidae and Bodonidae (Eugelenozoa: Kinetoplastida) was conducted using a variety of methods. Unlike previous analyses using unrooted trees and/or smaller numbers of sequences, the analysis did not support monophyly of the genus Trypanosoma, which includes the major human parasites T. cruzi (cause of Chagas' disease) and T. brucei (cause of African sleeping sickness). The section Salivaria of the genus Trypanosoma fell outside a cluster that includes the section Stercoraria of the genus Trypanosoma, along with members of the genera Leishmania, Endotrypanum, Leptomonas, Herpetomonas, Phytomonas, Crithidia, and Blastocrithidia. The phylogenetic analysis also indicated that the genera Bodo, Cryptobia, Leptomonas, Herpetomonas, Crithidia, and Blastocrithidia are polyphyletic. The results suggested that parasitism of vertebrates has probably arisen independently a number of times within the Trypanosomatidae.

Animals↗
PubMed2003

Class I molecules with similar peptide-binding specificities are the result of both common ancestry and convergent evolution.

HLA class I molecules can be classified into supertypes associated with overlapping peptide-binding motifs and repertoires. Herein, overlaps in peptide-binding and T-cell recognition repertoires were demonstrated between mouse and human molecules. Since rodent and primate lineages separated before the current allelic variation of mouse and human class I molecules, these data demonstrate that supertypic specificities originated by convergent evolution. Phylogenetic and structural analyses demonstrated that convergent evolution also occurs amongst primates and within the human species, resulting from the selection of different pocket structures having similar specificity or independent repeated selection of the same pocket structure.

Amino Acid Motifs↗
PubMed2003

Evolution of vertebrate voltage-gated ion channel alpha chains by sequential gene duplication.

Phylogenetic analysis of alpha chains of voltage-gated ion channels revealed that extensive gene duplication has occurred among both Ca(2+) and Na(+)-channels since the origin of vertebrates. Rather than showing a pattern of gene duplication consistent with the hypothesis of polyploidization early in vertebrate history, both Ca(2+) and Na(+) channels showed patterns of sequential gene duplication associated with specialization of the gene products. In the case of Na(+) channels, the phylogeny supported the hypothesis that the ancestral vertebrate gene had an expression pattern including both central and peripheral nervous system cells and that duplication of vertebrate Na(+) channel genes has repeatedly been followed by specialization for the central nervous system, the peripheral nervous system, or muscle cells. Thus, cephalization in vertebrate evolution has been accompanied by specialization of this important family of neuromuscular proteins along the central-peripheral axis.

Animals↗
PubMed2003

The temporal distribution of gene duplication events in a set of highly conserved human gene families.

Using a data set of protein translations associated with map positions in the human genome, we identified 1520 mapped highly conserved gene families. By comparing sharing of families between genomic windows, we identified 92 potentially duplicated blocks in the human genome containing 422 duplicated members of these families. Using branching order in the phylogenetic trees, we timed gene duplication events in these families relative to the primate-rodent divergence, the amniote-amphibian divergence, and the deuterostome-protostome divergence. The results showed similar patterns of gene duplication times within duplicated blocks and outside duplicated blocks. Both within and outside duplicated blocks, numerous duplications were timed prior to the deuterostome-protostome divergence, whereas others occurred after the amniote-amphibian divergence. Thus, neither gene duplication in general nor duplication of genomic blocks could be attributed entirely to polyploidization early in vertebrate history. The strongest signal in the data was a tendency for intrachromosomal duplications to be more recent than interchromosomal duplications, consistent with a model whereby tandem duplication-whether of single genes or of genomic blocks-may be followed by eventual separation of duplicates due to chromosomal rearrangements. The rate of separation of tandemly duplicated gene pairs onto separated chromosomes in the human lineage was estimated at 1.7 x 10(-9) per gene-pair per year.

Animals↗
PubMed2003

Parallel evolution by gene duplication in the genomes of two unicellular fungi.

Phylogenetic analysis of conserved gene families in fission yeast Schizosaccharomyces pombe and brewer's yeast Saccharomyces cerevisiae showed that gene duplications have occurred independently in the same families in each of these two lineages to a far greater extent than expected by chance. These species represent distinct lineages of the phylum Ascomycota that independently evolved a "yeast" life cycle with a unicellular thallus that reproduces by budding, and many of the genes that have duplicated independently in the two lineages are known to be involved in crucial aspects of this life cycle. Parallel gene duplication thus appears to have played a role in the independent origin of similar adaptations in the two species. The results indicate that using phylogenetic analysis to test for parallel gene duplication in different species may help in identifying genes responsible for similar but independently evolved adaptations.

Evolution, Molecular↗
PubMed2003

2R or not 2R: testing hypotheses of genome duplication in early vertebrates.

The widely popular hypothesis that there were two rounds of genome duplication by polyploidization early in vertebrate history (the 2R hypothesis) has been difficult to test until recently. Among the lines of evidence adduced in support of this hypothesis are relative genome size, relative gene number, and the existence of genomic regions putatively duplicated during polyploidization. The availability of sequence for a substantial portion of the human genome makes possible the first rigorous tests of this hypothesis. Comparison of gene family size in the human genome and in invertebrate genomes shows no evidence of a 4:1 ratio between vertebrates and invertebrates. Furthermore, explicit phylogenetic tests for the topology expected from two rounds of polyploidization have revealed alternative topologies in a substantial majority of human gene families. Likewise, phylogenetic analyses have shown that putatively duplicated genomic regions often include genes duplicated at widely different times over the evolution of life. The 2R hypothesis thus can be decisively rejected. Rather, current evidence favors a model of genome evolution in which tandem duplication, whether of genomic segments or of individual genes, predominates.

Animals↗
PubMed2003

Parallel evolution by gene duplication in the genomes of two unicellular fungi.

Phylogenetic analysis of conserved gene families in fission yeast Schizosaccharomyces pombe and brewer's yeast Saccharomyces cerevisiae showed that gene duplications have occurred independently in the same families in each of these two lineages to a far greater extent than expected by chance. These species represent distinct lineages of the phylum Ascomycota that independently evolved a "yeast" life cycle with a unicellular thallus that reproduces by budding, and many of the genes that have duplicated independently in the two lineages are known to be involved in crucial aspects of this life cycle. Parallel gene duplication thus appears to have played a role in the independent origin of similar adaptations in the two species. The results indicate that using phylogenetic analysis to test for parallel gene duplication in different species may help in identifying genes responsible for similar but independently evolved adaptations

Evolution, Molecular↗
PubMed2002

Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor (hFLVCR) gene: evidence for block duplications and de novo gene formation within duplicons of the hFLVCR locus.

In this paper we sought to analyze the genomic structure and context of human feline leukemia virus subgroup C receptor (hFLVCR), a human glucarate transporter-like gene at chromosome 1q31, and compare it to that of a paralog (FLVCR14q) at chromosome 14q24. Splicing, polyadenylation, and expression patterns, as estimated by in silico analysis, differed between the two FLVCR genes despite their similar genomic structures, suggesting active and independent evolution of transcriptional and messenger RNA processing patterns after gene duplication. Promoter activity was bi-directional for hFLVCR, but not for its 14q paralog. The upstream 1q transcribed sequences were determined to comprise a novel gene of unknown function, LQK1. Annotation of contigs centered at hFLVCR and FLVCRL14q also revealed highly conserved gene clusters on chromosomes 1 and 14, inferred to result from a duplication. The clusters contained members of the FLVCR, Angel (KIAA0759), JDP, p21SNFT, and TGF- families, as well as two uncharacterized families. The genome-wide locations of both previously recognized and four de novo in silico predicted genes belonging to these seven families were determined. Phylogenetic analyses of these families were consistent with the hypothesis that the 1q/14q duplication occurred early within, or immediately prior to the vertebrate divergence, after the protostome-deuterostome divergence but before the amniote-amphibian divergence.

3' Untranslated Regions↗
PubMed2002

Molecular evolution of the NF-kappaB signaling system.

The mechanisms of innate immunity in vertebrates show certain overall resemblances to immune mechanisms of insects. Two hypotheses have been proposed to explain these resemblances. (1) According to the evolutionary continuity hypothesis, innate immune mechanisms evolved in the common ancestor of vertebrates and insects and have been conserved since that time. (2) In the independent-evolution hypothesis, the mechanisms of innate immunity in vertebrates evolved independently from invertebrate immune mechanisms. Phylogenetic analysis of five gene families (Pelle, Rel, IkappaB, Toll, and TRAF) whose members are involved in NF-kappaB signaling in vertebrates and insects were used to decide between these hypotheses. The phylogenies of the Rel and TRAF families strongly supported independent evolution of immune functions in vertebrates and invertebrates, and, except for a possible case in the Pelle family, orthologous molecules having immune functions in both vertebrates and invertebrates were not found. The results suggest that NF-kappaB represents an ancient, generalized signaling system that has been co-opted for immune system roles independently in vertebrate and insect lineages.

Amino Acid Sequence↗
PubMed2002

Origin and evolution of viral interleukin-10 and other DNA virus genes with vertebrate homologues.

Phylogenies of gene families including members in both vertebrates and DNA viruses of the poxvirus and/or herpesvirus families showed that the viral genes originated at widely different times over the history of life. Certain of these viral genes (for example, the genes encoding the large and small subunits of ribonucleoside-diphosphate reductase) originated before animals diverged from fungi, while others originated much more recently. The most striking examples of recent origin involved viral genes encoding the cytokine interleukin-10 (IL-10), which originated independently in viruses at least three times since the divergence of the orders of eutherian mammals, presumably by viral capture of host genes. In certain domains, viral IL-10 genes showed significantly higher rates of nonsynonymous substitution than their nearest mammalian homologues. Though the mutation rate in these viral genes is up to 20 times that of the corresponding mammalian genes, a high mutation rate alone did not account for these differences because they were not seen in all domains. Rather, in certain domains it appears that functional constraints present in the case of mammalian IL-10 are relaxed in the case of the viral homologues. Furthermore, a nonrandom pattern of change with respect to amino acid residue charge in the N-terminal portion of the mature protein has occurred repeatedly in independently derived viral IL-10 genes, strongly suggesting that positive selection has led to divergence of this functionally important domain in viral IL-10.

Antigens, CD↗
PubMed2002

Characterization and phylogenetic relationship of prosimian MHC class I genes.

MHC class I cDNA sequences from the most divergent primate group of extant primates compared to human, the suborder Strepsirrhini (prosimians), are described. The sequences are derived from the gray mouse lemur (Microcebus murinus) and the ring-tailed lemur (Lemur catta), which are members of the malagasy Lemuriformes, as well as from the pygmy slow loris (Nycticebus pygmaeus), a prosimian from East Asia. The M. murinus sequences have been analyzed in detail. Analysis of the expression level, G/C content, and synonymous vs. nonsynonymous substitution rates in the peptide-binding region codons suggests that these cDNA clones represent classical class I (class Ia) genes. According to Southern blot analysis, the genome of the gray mouse lemur might contain about 10 class I genes. In gene tree analysis, the strepsirrhine class Ia genes described here cluster significantly separately from the known class I genes of Catarrhini (humans, apes, Old World monkeys) and Platyrrhini (New World monkeys) species, suggesting that the class I loci of Simiiformes arose by gene duplications which occurred after the divergence of prosimians.

Amino Acid Sequence↗
PubMed2002

Adaptive evolution after gene duplication.

One of the two ribonuclease genes in a leaf-eating monkey has adapted to a role in the digestion of bacterial RNA. Following duplication of the ancestral ribonuclease gene, adaptation occurred through a series of changes in the amino acid sequence of the protein it encodes. This example is a good illustration of how specialization of protein function after gene duplication can be as source of novel protein functions.

Adaptation, Biological↗
PubMed2002

Evolution of the human killer cell inhibitory receptor family.

Phylogenetic analysis of different domains of human natural killer cell inhibitory receptors (KIR) implicated both intragenic duplication and deletion of exons and interlocus recombination in the evolution of these receptors. In phylogenies of the extracellular immunoglobulin (Ig) superfamily C2-set domains and of the pre-membrane (PM) domain, KIR receptors having two C2-set domains and those having three such domains tended to form separate clusters. However, the phylogenies of the transmembrane (TM) and cytoplasmic (CYT) domains showed quite different topologies, suggesting that major sites of interlocus recombination have been between exon 6 (encoding PM) and exon 7 (encoding TM) and between exon 7 and exons 8-9 (encoding CYT). Examination of the pattern of nucleotide substitution in the exons encoding Ig C2-set domains supported the hypothesis that positive Darwinian selection has acted to diversify the residues within these domains that are involved in contact with class I MHC molecules.

Amino Acid Sequence↗
PubMed2002

Extensive polymorphism and ancient origin of Plasmodium falciparum.

DNA sequence data reveal extensive polymorphism in the virulent, human malaria parasite Plasmodium falciparum. The extent of polymorphism at apparently neutral-evolving loci points to a common ancestor for this species that is no more recent than approximately 150,000-200,000 years ago. In addition, there is evidence of balanced polymorphisms at certain antigen-encoding loci, some of which have been maintained for millions of years. Thus, we can reject the hypothesis that this species underwent a recent extreme bottleneck (i.e. one in which the population was reduced to a single haploid genotype). However, it is possible that less-severe bottlenecks have occurred.

Animals↗
PubMed2002

Evolution of inhibitors of apoptosis in baculoviruses and their insect hosts.

The phylogenetic relationships of inhibitor of apoptosis (IAP) from insects and insect viruses were reconstructed and compared with the phylogeny of the viruses reconstructed on the basis of DNA polymerase species. The phylogeny supported the hypothesis that there were three IAP genes in the ancestor of the viral genus Nucleopolyhedrovirus (family Baculoviridae), but that there has been differential deletion of IAP genes in different lineages within this genus. An IAP gene from the granulovirus of the lepidopteran species Cydia pomonella (CpGV) was found to be a close relative of IAP genes from species of the insect order Lepidoptera, supporting the origin of this viral gene by capture of a host gene early in the evolution of Lepidoptera. The phylogeny supported the occurrence of least one other independent event of capture of an IAP gene by a virus and suggested the possibility of at least two other such events. Contrary to the prediction that host genes with viral homologues should experience an enhanced rate of amino acid replacement, no acceleration of evolutionary rate was detectable in these lepidopteran genes, which showed particularly low rates of non-synonymous nucleotide substitution in functionally important domains.

Animals↗