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E N Moriyama

Publications and source records attributed to E N Moriyama.

11 recordsLinked to original sources
PubMed1992

Structure of the bovine ETB endothelin receptor gene.

The structure of the gene encoding the bovine type B endothelin receptor (ETB) has been established and compared with those of other heptahelical receptors. The gene is present as a single copy in the bovine genome, as demonstrated by Southern blot analysis, and spans at least 36 kb. The coding region is divided into 7 exons separated by 6 introns, one of which is more than 23 kb in length. The exons correspond well to the structural domains of the receptor: the first exon encodes the first and second transmembrane domains, and each of the following transmembrane domains is encoded by a separate exon. The portion of the ETB protein sequence encoded by exon 3 is quite different from the corresponding ETA sequence, suggesting that this region is responsible for the distinct ligand specificities of the two receptor subtypes. The second intron interrupts the canonical Asp-Arg-Tyr sequence, which is located at the end of the third transmembrane domain of the heptahelical receptors, as with the substance P, substance K, dopamine D2 and dopamine D3 receptor genes. To map the 5' region of the gene and determine the start of transcription, primer-extended cDNAs were cloned and sequenced: multiple start sites were deduced with no apparent TATA box in the expected upstream region. Similar results were obtained by ribonuclease protection analysis.

Animals↗
PubMed1992

Rates of synonymous substitution and base composition of nuclear genes in Drosophila.

We compared the rates of synonymous (silent) substitution among various genes in a number of species of Drosophila. First, we found that even for a particular gene, the rate of synonymous substitution varied considerably with Drosophila lineages. Second, we showed a large variation in synonymous substitution rates among nuclear genes in Drosophila. These rates of synonymous substitution were correlated negatively with C content and positively with A content at the third codon positions. Nucleotide sequences were also compared between pseudogenes and their functional homologs. The C content of the pseudogenes was lower than that of the functional genes and the A content of the former was higher than that of the latter. Because the synonymous substitution for functional genes and the nucleotide substitution for pseudogenes are exempted from any selective constraint at the protein level, these observations could be explained by a biased pattern of mutation in the Drosophila nuclear genome. Such a bias in the mutation pattern may affect the molecular clock (local clock) of each nuclear gene of each species. Finally, we obtained the average rates of synonymous substitution for three gene groups in Drosophila; 11.0 x 10(-9), 17.5 x 10(-9) and 27.1 x 10(-9)/site/year.

Animals↗
PubMed1991

Mutation pattern of human immunodeficiency virus gene.

Human immunodeficiency viruses (HIVs) show extensive genetic variation. This feature is the fundamental cause of pathogenicity of HIVs and thwarts efforts to develop effective vaccines. To understand the mutation mechanism of these viruses, we analysed nucleotide sequences of env and gag genes of the viruses by use of molecular evolutionary methods and estimated the direction and frequency of nucleotide substitutions. Results obtained showed that the frequency of changes between A and G was extremely high and the mutation pattern of HIVs was distinct from those of nuclear genes of their host cells. This distinction may be caused by the characteristics of the reverse transcription of HIVs. The mutation pattern obtained would be helpful to construct effective antiviral drugs.

Base Sequence↗
PubMed1990

Evolutionary origin of human and simian immunodeficiency viruses.

From what viruses the human immunodeficiency viruses (HIVs) originated is an extremely controversial question. To address this question, we have analyzed nucleotide sequences of simian immunodeficiency viruses (SIVs) and HIVs by using the techniques for understanding molecular evolution. In particular, we compared the nucleotide sequences of whole genomes, gene region by gene region, between a given pair of viruses, including four types of SIVs--isolated from mandrills (Papio sphinx), African green monkeys (Cercopithecus aethiops), sooty mangabeys (Cercocebus atys), and rhesus macaques (Macaca mulatta)--as well as HIVs. Phylogenetic trees for all gene regions examined showed that the present HIVs may have emerged as different variants of SIVs of Old World monkeys, possibly from recombination between viruses related to SIVs.

Biological Evolution↗
PubMed1990

Molecular clock of viral evolution, and the neutral theory.

Evolution of viral genes is characterized by enormously high speed compared with that of nuclear genes of eukaryotic organisms. In this paper, the evolutionary rates and patterns of base substitutions are examined for retroviral oncogenes, human immunodeficiency viruses (HIV), hepatitis B viruses (HBV), and influenza A viruses. Our results show that the evolutionary process of these viral genes can readily be explained by the neutral theory of molecular evolution. In particular, the neutral theory is supported by our observation that synonymous substitutions always much predominate over nonsynonymous substitutions, even though the substitution rate varies considerably among the viruses. Furthermore, the exact correspondence between the high rates of evolutionary base substitutions and the high rates of production of mutants in RNA viruses fits very nicely to the prediction of the theory. The linear relationship between substitution numbers and time was examined to evaluate the clock-like property of viral evolution. The clock appears to be quite accurate in the influenza A viruses in man.

Biological Evolution↗
PubMed1990

Establishment of a phylogenetic survey system for AIDS-related lentiviruses and demonstration of a new HIV-2 subgroup.

We designed a universal primer (UNIPOL) for DNA amplification of AIDS-related viruses. The phylogenetic tree constructed from the presumed sequences amplified with UNIPOL was representative of the tree calculated from whole pol gene sequences so far reported. UNIPOL was able to amplify the sequences of all four major groups of primate lentiviruses and also that of a distinct virus from a Ghanaian patient with an AIDS-related complex, designated GH-2. This strain scarcely hybridizes with known HIV/simian immunodeficiency virus (SIV) DNA probes. Sequence analysis of the only amplified fragment revealed rapidly that GH-2 was quite similar to the recently reported HIV-2ALT(D205) and that these two viruses form a new subgroup distint from known HIV-2 and SIVmac/SIVsm in the large HIV-2 group. This system will be useful for further phylogenetic study of various primate lentiviruses.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Sequence of a novel simian immunodeficiency virus from a wild-caught African mandrill.

Since the isolation of an HIV-2-related virus from captive macaques (SIVMAC), the origin of human immunodeficiency viruses, a much debated subject, has been attributed to monkeys. The sequence of SIVAGM, which is derived from a naturally infected African green monkey, shows equal relatedness to HIV-1 and HIV-2, suggesting that the derivation of these viruses from SIVAGM is unlikely. Recent sequence analysis of SIV from a captive sooty mangabey (SIVMAC), however, shows its close relatedness to HIV-2 and SIVMAC, indicating a possible origin of HIV-2 and SIVMAC from SIVSM (refs 4, 7, 9). We report here the sequence of a novel simian lentivirus, SIVMND, isolated from a wild-caught mandrill in Africa. It is distinct from the three other main groups, HIV-1, HIV-2/SIVMAC/SIVSM and SIVAGM, and therefore represents a fourth main group of primate lentiviruses. Phylogenetic analysis indicates that these four main virus groups might have diverged from a common ancestor at about the same time, long before the spread of AIDS in humans.

Animals↗
PubMed1989

Patterns of nucleotide substitutions and implications for the immunological diversity of human immunodeficiency virus.

Human immunodeficiency virus (HIV) exhibits immunological hypervariability, which has been an obstacle to successful production of effective anti-HIV vaccines. In this study, we estimated patterns of nucleotide and amino acid substitutions in the env gene of HIVs, with the aim of finding characteristics of the mechanism which generates the immunological diversity of the env protein of HIVs. We found that nucleotide changes between A and G are predominant compared to those between other nucleotides. Since this feature is consistent with the pattern of nucleotide substitutions of other retroviral genes but is quite different from those of most eukaryotic genes, a high rate of nucleotide substitution between A and G appears to be specific for retroviruses including HIVs. We discuss the biological relationship between this biased substitution and the mechanism generating hypervariability of epitopes on the env protein of HIVs.

Amino Acids↗
PubMed1989

Evolution of nested genes with special reference to cuticle proteins in Drosophila melanogaster.

One of the pupal cuticle protein (PCP) genes has been found within an intron of a Drosophila housekeeping gene (the Gart locus) that encodes three enzymes involved in the purine pathway. This intronic gene has been described as a gene within a gene, and the gene is now called a "nested" gene. Because the intronic PCP gene has sequence similarity with the larval cuticle protein (LCP) gene, it may have been derived from one of the LCP genes or their ancestral gene. We have studied possible phylogenetic relationships among these five genes by comparing nucleotide sequences of four LCP genes with that of the PCP gene. The results obtained suggest that the PCP gene may have originated from an ancestral gene before duplication of the LCP genes occurred. Using the number of synonymous (silent) substitutions, we then estimated the divergence time between the PCP gene and the LCP genes to be about 70 million years (Myr). The divergence time estimated is much larger than that for the sibling species of D. melanogaster (about 2.5 Myr), indicating that the "nested" gene structure can be seen not only in Drosophila melanogaster, but also in other distantly related Drosophila species.

Amino Acid Sequence↗
PubMed1989

Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences.

An analysis of molecular phylogeny was undertaken to examine whether the evolution of the hepadnavirus family is host-dependent. Using the nucleotide sequences of 18 strains, we constructed phylogenetic trees. The trees obtained show that all 12 strains of hepatitis B virus can be classified into four subgroups that are not compatible with conventional subtypes. We estimated the rate of synonymous (silent) substitution for hepatitis B virus to be 4.57 x 10(-5) per site per year. Applying this rate to the phylogenetic tree, we estimated that duck hepatitis B virus diverged from a common ancestor about 30,000 years ago at the earliest, that woodchuck hepatitis virus and ground squirrel hepatitis virus diverged about 10,000 years ago, and that hepatitis B virus diverged within the last 3000 years. Because these divergence times of the viruses are much more recent than those of the host species, it suggests that the hepadnavirus family evolved independently of host-species divergence.

Animals↗