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At least 19 recordsLinked to original sources
PubMed1988

The evolutionary conservation of DNA polymerase alpha.

The evolutionary conservation of DNA polymerase alpha was assessed by immunological and molecular genetic approaches. Four anti-human KB cell DNA polymerase alpha monoclonal antibodies were tested for their ability to recognize a phylogenetically broad array of eukaryotic DNA polymerases. While the single non-neutralizing antibody used in this study recognizes higher mammalian (human, simian, canine, and bovine) polymerases only, three neutralizing antibodies exhibit greater, but variable, extents of cross-reactivity among vertebrate species. The most highly cross-reactive antibody recognizes a unique epitope on a 165-180 kDa catalytic polypeptide in cell lysates from several eukaryotic sources, as distant from man as the amphibians. Genomic Southern hybridization studies with the cDNA of the human DNA polymerase alpha catalytic polypeptide identify the existence of many consensus DNA sequences within the DNA polymerase genes of vertebrate, invertebrate, plant and unicellular organisms. These findings illustrate the differential evolutionary conservation of four unique epitopes on DNA polymerase alpha among vertebrates and the conservation of specific genetic sequences, presumably reflective of critical functional domains, in the DNA polymerase genes from a broad diversity of living forms.

Animals↗
PubMed2023

Utilizing evolutionary conservation to detect deleterious mutations and improve genomic prediction in cassava.

INTRODUCTION: Cassava (Manihot esculenta) is an annual root crop which provides the major source of calories for over half a billion people around the world. Since its domestication ~10,000 years ago, cassava has been largely clonally propagated through stem cuttings. Minimal sexual recombination has led to an accumulation of deleterious mutations made evident by heavy inbreeding depression. METHODS: To locate and characterize these deleterious mutations, and to measure selection pressure across the cassava genome, we aligned 52 related Euphorbiaceae and other related species representing millions of years of evolution. With single base-pair resolution of genetic conservation, we used protein structure models, amino acid impact, and evolutionary conservation across the Euphorbiaceae to estimate evolutionary constraint. With known deleterious mutations, we aimed to improve genomic evaluations of plant performance through genomic prediction. We first tested this hypothesis through simulation utilizing multi-kernel GBLUP to predict simulated phenotypes across separate populations of cassava. RESULTS: Simulations showed a sizable increase of prediction accuracy when incorporating functional variants in the model when the trait was determined by<100 quantitative trait loci (QTL). Utilizing deleterious mutations and functional weights informed through evolutionary conservation, we saw improvements in genomic prediction accuracy that were dependent on trait and prediction. CONCLUSION: We showed the potential for using evolutionary information to track functional variation across the genome, in order to improve whole genome trait prediction. We anticipate that continued work to improve genotype accuracy and deleterious mutation assessment will lead to improved genomic assessments of cassava clones.

cassava (Manihot esculenta)↗
PubMed1985

Evolutionary conservation of ribosomal protein mRNA sequences: application for expansion of corresponding cDNA and gene libraries.

Cloned cDNAs, containing ribosomal protein sequences from mouse (five cDNAs) or Xenopus laevis (six cDNAs), were used to estimate the evolutionary conservation, from insects to mammals, of the corresponding mRNA sequences. Northern blot analysis reveals a variable degree of homology between these sequences in different eukaryotes. Thus, among the ribosomal protein cDNA clones utilized, some exhibit complete, others partial, and a few no interphyla cross-hybridization. Melting profile analysis was employed to quantitate this homology. It is proposed that for expansion of eukaryotic ribosomal cDNA and gene libraries, one can exploit the interspecies homology of the corresponding sequences. However, the diverse evolutionary conservation of individual ribosomal protein gene sequences should be taken into account.

Animals↗
PubMed1992

Missense mutations and evolutionary conserved amino acids at the human hypoxanthine phosphoribosyl-transferase locus.

Molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in Lesch-Nyhan and gout patients, and somatic mutation in 6-thioguanine resistant T-lymphocytes from healthy individuals. The pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites Schistosoma mansoni and Plasmodium falciparum. Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency). This observation supports the notion that evolutionary conserved amino acids constitute functionally important sites in the hprt enzyme, and missense mutations affecting these amino acids will often lead to complete loss of enzyme activity. Substitutions of 'non-conserved' amino acids cause less severe hprt-deficiency (as seen in the gout patients), or may even escape clinical diagnosis. These considerations are important for the understanding of structure-activity relationships in the hprt protein, possible differences between hprt mutational spectra in germ-line and somatic cells, and the mutational spectra induced by specific exogeneous mutagens.

Amino Acid Sequence↗
PubMed1985

Evolutionary conservation of brain Thy-1 glycoprotein in vertebrates and invertebrates.

The evolutionary conservation of brain Thy-1 glycoprotein in 24 vertebrate and invertebrate species has been investigated by means of a soluble phase radioimmunoassay (RIA) and by the "Western blot" technique. The brain glycoproteins from virtually all the vertebrate species inhibited the precipitation of mouse Thy-1.1 by a rabbit anti-rat Thy-1 antiserum. Most reagents also inhibited the binding of a mouse anti-rat Thy-1 monoclonal antibody to rat Thy-1. Whole tissue glycoproteins from earthworm, snail and oyster and ganglia glycoproteins of a locust species were also found to be inhibitory. Western blotting analysis on NaDod SO4 polyacrylamide gel electrophoresis under reducing conditions revealed a Thy-1 homologous molecule (22-25 KD) in mammals, birds, fish, reptiles and invertebrate species. The snail Thy-1-like molecule was eluted from the gel and was shown to specifically inhibit the serological reaction. The rabbit anti-rat Thy-1 antiserum also detected a doublet molecule of approximately 85,000 KD, which is conserved in all species, including yeast and bacteria. The origin and nature of the presumed glycoproteins is unknown. Our results suggest that the Thy-1 molecule has been conserved throughout metazoan evolution and that the Thy-1 gene is the most conserved among the immune related genes (immunoglobulins, beta 2-microglobulin and major histocompatibility) which share extensive amino acid homology.

Animals↗
PubMed1992

Evolutionary conservation of the dystrophin central rod domain.

Dystrophin cDNA fragments encoding the C-terminal repeats of the central rod region have been expressed as fusion proteins. The polyclonal antisera raised to the purified fusion proteins have been characterized and neither antiserum cross-reacted with dystrophin-related protein. Antisera detected dystrophin with molecular mass close to that of the human in all terrestrial vertebrates and amphibia studied. Experiments with antisera to the N-terminal region of the dystrophin rod confirmed that epitopes to the rod region were conserved during this evolutionary period and the length of this domain remained unaltered.

Animals↗
PubMed1990

The -175T----C mutation increases promoter strength in erythroid cells: correlation with evolutionary conservation of binding sites for two trans-acting factors.

A point mutation at position -175 has been detected in Agamma as well as Ggamma globin genes in individuals with hereditary persistence of fetal hemoglobin (HPFH). To prove that this single point mutation results in increased promoter strength, we transfected erythroid and nonerythroid cell lines with constructs containing normal and mutant promoters linked to the bacterial chloramphenicol acetyl transferase (CAT) gene. Differences in transfection efficiency were controlled by cotransfection of pRSVgpt. In K562 erythroleukemia cells, the -175 HPFH promoter directed three- to fourfold more CAT activity than its wild type counterpart. However, in HeLa cells the two promoters were similar in strength. The -195 to -165 region of the gamma-globin promoter contains binding sites for two proteins: a ubiquitously distributed octamer binding protein, OBP, and the erythroid-specific protein, GF-1. We find that while the GF-1 binding site is highly conserved among related primate gamma-globin genes, the octamer binding site is not. The evolutionary conservation of GF-1 as well as its erythroid-specific distribution suggest that this protein is important in gamma-globin gene expression. A role for OBP in the regulation of gamma-globin, if any, must have arisen recently in primate evolution.

Animals↗
PubMed2026

Evolutionary conservation of heat shock proteins in Blattodea and their roles in wing morphogenesis and ovarian development of Blattella germanica.

Heat shock proteins (Hsps) are essential molecular chaperones for protein homeostasis and stress responses. However, the Hsp repertoires and functions in Blattodea remain underexplored. Our genome-scale survey of nine Blattodea species revealed 37-46 conserved Hsp90, Hsp70, and DNAJ (Hsp40) genes, with DNAJ the most abundant and Hsp90 the least. Phylogenetic analysis confirmed the evolutionary conservation of three Hsp90, seven Hsp70, and 29 DNAJ subclades in Blattodea. Selection pressure analysis revealed predominant purifying selection (dN/dS&#xa0;&#x226a;&#xa0;1) across lineages, strongest in DNAJ and highest in Hsp90 conservation. In Blattella germanica, expression of six representative BgHsp genes progressively increased during development, peaking in fifth-instar nymphs. Tissue expression profiling revealed that BgHspA1-2/3/4 were predominantly expressed in legs, BgDNAJB5 and BgHsp90AB1-2 were enriched in the fat body, and BgHsp90AB1 was highly expressed in the head. dsRNA injection targeting conserved Hsp gene regions achieved 61.9-94.1% knockdown of all six target genes. RNAi knockdown of six BgHsp genes disrupted wing morphogenesis, causing distinct phenotypes: wing whitening (56.7%, dsBgHspA1-4), unequal length (66.7%, dsBgHspA1-3; 76.7%, dsBgDNAJB5), and wing wrinkling (70%, dsBgHspA1-2; 63.3%, dsBgHsp90AB1; 76.7%, dsBgHsp90AB1-2). During ovarian formation, the developmental delay was most severe in the dsBgHsp90AB1 group, moderate in the dsBgHsp90AB1-2 and dsBgHspA1-2/3/4 groups, and weakest in the dsBgDNAJB5 group. Besides, knockdown significantly downregulated key developmental genes (apterous-a, nubbin, scalloped, ultrabithorax, wingless, and vitellogenin). These findings provide a reference for understanding the evolutionary patterns of Hsps in Blattodea, and offer mechanistic insights into the developmental regulation mediated by Hsps in this important public-health pest.

Animals↗
PubMed1991

Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as "spacer" elements.

We report 31 point mutations in the factor IX gene and explore the relationship between the level of evolutionary conservation of an amino acid and the probability of a mutation causing hemophilia B. From our total sample of 125 hemophiliacs and from those reported by others, we identify 95 independent missense mutations, 94 of which occur at amino acids that are evolutionarily conserved in the available mammalian factor IX sequences. The likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X, and protein C. Most of the possible missense mutations in generically conserved residues (i.e., those conserved in factor IX and in all the related proteases) should cause disease. In contrast, missense mutations in factor IX-specific residues (i.e., those conserved in human, cow, dog, and mouse factor IX but not in the related proteases) are sixfold less likely to cause disease. Missense mutations at nonconserved residues are 33-fold less likely to cause disease. At least three models are compatible with these observations. A comparison of sequence alignments from four and nine species of factor IX and an examination of the missense mutations occurring at CpG residues suggest a model in which most residues fall on opposite ends of a spectrum. In about 40% of residues, virtually any missense mutation in a minority of the residues will cause disease, while virtually no missense mutations will cause disease in most of the remaining residues. Thus, many of the residues in factor IX are spacers; that is, the main chains are presumably necessary to keep other amino acid interactions in register, but the nature of the side chain is unimportant.

Amino Acid Sequence↗
PubMed1989

Evolutionary conservation of homeodomain-binding sites and other sequences upstream and within the major transcription unit of the Drosophila segmentation gene engrailed.

The engrailed (en) gene functions throughout Drosophila development and is expressed in a succession of intricate spatial patterns as development proceeds. Normal en function relies on an extremely large cis-acting regulatory region (70 kilobases). We are using evolutionary conservation to help identify en sequences important in regulating patterned expression. Sequence comparison of 2.6 kilobases upstream of the en coding region of D. melanogaster and D. virilis (estimated divergence time, 60 million years) showed that 30% of this DNA occurs in islands of near perfect sequence conservation. One of these conserved islands contains binding sites for homeodomain-containing proteins. It has been shown genetically that homeodomain-containing proteins regulate en expression. Our data suggested that this regulation may be direct. The remaining conserved islands may contain binding sites for other regulatory proteins.

Animals↗
PubMed1992

Complete cDNA sequence of chicken vigilin, a novel protein with amplified and evolutionary conserved domains.

The complete cDNA (4375 bp), coding for a new protein called vigilin, was isolated from chicken chondrocytes. The cDNA shows an open reading frame of 1270 amino acids which are organized in 14 tandemly repeated homologous domains. Each domain consists of two subdomains, one with a conserved sequence motif of 35 amino acids (subdomain A) and another one with a presumptive alpha-helical structure of 21-33 amino acids (subdomain B). 149 amino acids at the N-terminus and 71 amino acids at the C-terminus of vigilin do not show the characteristic domain structure. No sequence characteristic of a signal peptide has been found, which argues for an intracellular localisation of vigilin. Vigilin is highly expressed in freshly isolated chicken chondrocytes but little in chondrocytes after prolonged time in culture. Vigilin mRNA exists in two size species, 4.4 kb and 6.5 kb in length due to the usage of different polyadenylation sites. Comparison of the vigilin sequence with data bases showed a remarkable similarity to protein HX from Saccharomyces cerevisiae [Delahodde, A., Becam, A. M., Perea, J. & Jacq, C. (1986) Nucleic Acids Res. 14, 9213-9214]. The yeast protein consists of eight homologous domains with 11 conserved amino acid residues within a set of 35 amino acids. The N-terminal and C-terminal regions of vigilin and protein HX do not reveal any sequence similarity. These results, together with the demonstration of the characteristic vigilin sequence motif in a human cDNA clone, suggest that the repeats represent evolutionary conserved autonomous domains within a family of proteins found in yeast, chicken and man.

Amino Acid Sequence↗
PubMed1989

Prothymosin alpha is an evolutionary conserved protein covalently linked to a small RNA.

A 13 kDa protein, covalently linked to a small RNA from the cytoplasm of mouse cells, was studied. Sequence analysis of its tryptic peptides revealed that the RNA-linked protein is identical to prothymosin alpha. Very similar RNA-protein complexes were identified in human, bovine and yeast cells. Tryptic peptide maps of 125I-labelled RNA-linked proteins of diverse origin demonstrated their marked similarity, thus indicating high evolutionary conservation of prothymosin alpha from yeast to man.

Amino Acid Sequence↗
PubMed1991

Evolutionary conservation and chromosomal localization of flvi-1.

A locus in feline DNA, termed flvi-1, has been identified as harboring retroviral integrations commonly found in natural feline lymphomas induced by infection with feline leukemia virus (FeLV). Southern blot analysis of human and murine DNA using restriction fragments representing flvi-1 demonstrates its phylogenetic conservation among mammals, flvi-1 is localized to murine chromosome 2, proximal portion of band E, by in situ hybridization to metaphase chromosomes. This position is adjacent to that of another putative proto-oncogene, sfpi-1, although probes representing flvi-1 and sfpi-1 do not cross-hybridize. The repeated implication of flvi-1 in natural feline leukemogenesis, its evolutionary conservation and its chromosomal position support the hypothesis that flvi-1 may represent a previously unidentified protooncogene.

Animals↗
PubMed1987

Frog brain and liver show evolutionary conservation of tissue-specific differences among insulin receptors.

The insulin receptors of frog brain and liver show features typical of other insulin receptors with regard to affinity and specificity of binding to insulins and proinsulin, solubility in Triton X-100, binding to and elution from wheat germ agglutinin, and insulin-sensitive tyrosine kinase activity. Likewise, the brain and liver receptors differ from one another in electrophoretic mobility and susceptibility to treatment with neuraminidase, analogous to brain and liver receptors of reptiles, birds, and mammals; while the functional implications of these differences are unknown, their evolutionary conservation for 400-500 million years suggests the possibility that they might have importance.

Animals↗
PubMed1991

Evolutionary conservation of the spliceosomal protein, U2B''.

U1 and U2snRNPs play key roles in pre-mRNA splicing. The interactions between the U1 and U2snRNP-specific proteins, U1A, U2A' and U2B'' and their respective UsnRNAs are of interest both to elucidate their roles in splicing, and as models to study RNA-protein interactions. We have cloned a full-length cDNA, encoding U2B'', from potato. This is the first report of a sequence for a plant UsnRNP protein. The plant U2B'' sequence exhibits extensive similarity with the human U2B'' protein at both the DNA and amino acid levels. The evolutionary conservation at the protein level, particularly in sequences implicated in determining specific binding to U2snRNA, suggests conservation of U2B'' function from plants to man. The significance of amino acid substitutions in the RNP-80 motif with respect to U2snRNA binding in plants is discussed.

Amino Acid Sequence↗
PubMed1989

Characterization of an alternative exon of the murine T cell receptor beta-chain. Pattern of expression and evolutionary conservation.

In this report, we characterize an alternate gene element of the murine TCR beta-chain. First, we have looked at the expression of the alternate exon, C beta 0, in normal T cell clones, as well as in fetal vs adult whole thymus. The C beta 0 exon is expressed in only 1% or less of TCR-beta messages in four of four mature T cell clones examined. C beta 0 is found at 10-fold higher levels in both fetal and adult thymus mRNA. Thus C beta 0 is developmentally regulated by T cells, although expression of the alternate exon is relatively constant from the fetal thymus to the adult thymus. Second, evolutionary conservation of the C beta 0 gene element was studied in both the rat and the human. The rat beta-locus contains a gene element highly homologous to the mouse C beta 0 gene, but the rat C beta 0 gene contains mutations in both splice sites that probably prevent the gene element from being spliced into mRNA. We have also sequenced the first exon of rat C beta 1, and find that the C beta 0 exon and the intron around C beta 0 are conserved between rat and mouse to the same level as the C beta 1 coding region. The intron around C beta 1, in contrast, shows the decrease in conservation between the two species that is expected for a noncoding region. Analysis of the putative C beta 0-containing region in the human reveals no sequences homologous to the C beta 0 gene element. Because the mouse is the only species that has conserved a functional C beta 0 gene, we conclude that the C beta 0 exon does not play a general role in T cell development.

Amino Acid Sequence↗
PubMed1989

Transmembrane topography and evolutionary conservation of synaptophysin.

Synaptophysin is the major integral membrane protein of small synaptic vesicles. Its primary structure deduced from rat and human complementary DNA sequences predicts that synaptophysin contains four transmembrane regions and a carboxyl-terminal domain having a novel repetitive structure. To elucidate the transmembrane organization of this protein in the synaptic vesicle, five antipeptide antibodies were raised. The site-specific antibodies were used to map the cognate sequences to the cytoplasmic or intravesicular side of the synaptic vesicle membrane by determining the susceptibility of the epitopes to proteolysis. The results confirm a topographic model for synaptophysin in which the protein spans the vesicle membrane four times, with both the amino and carboxyl terminus being cytoplasmic. In addition, the evolutionary conservation of the synaptophysin domains was addressed as a function of their membrane localization. To this end the primary structure of bovine synaptophysin was determined. Sequence comparisons between bovine, rat, and human synaptophysin revealed that only the intravesicular loops showed a significant number of amino acid substitutions (22%), while the transmembrane regions and cytoplasmic sequences were highly conserved (3% substitutions). These results depict synaptophysin as a protein with multiple membrane spanning regions whose functional site is likely to reside in highly conserved intramembranous and cytoplasmic sequences.

Amino Acid Sequence↗
PubMed1985

Evolutionary conservation of fragile sites induced by 5-azacytidine and 5-azadeoxycytidine in man, gorilla, and chimpanzee.

Lymphocyte cultures from man, gorilla, and chimpanzee were treated with 5-azacytidine and 5-azadeoxycytidine. These cytidine analogues induce common fragile sites in the chromosome bands 1q42 and 19q13 of man. A rare fragile site is induced by 5-azadeoxycytidine in the band 1q24. The optimum conditions required for inducing these new fragile sites were determined by a series of experiments. The common fragile site in human chromosome 1q42 also exists in the gorilla and chimpanzee in the homologous band 1p32. The fragile site in human chromosome 19q13 was demonstrated in the gorilla in the homologous chromosome band 20q13. These are the first examples found of evolutionary highly conserved fragile sites in homologous chromosome bands in related primate species. The interaction between 5-azacytidine, 5-azadeoxycytidine, and chromosomal DNA; the evolutionary conservation of genes located within or closely adjacent to the fragile sites in the chromosome 1 of Hominoidea; and the phylogenetic origin of the two new common fragile sites are discussed.

Animals↗