Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Evolutionary analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed1989

Single amino acid exchanges in the finger domain impair the function of the Drosophila gene Krüppel (Kr).

Mutations in the Drosophila gene Krüppel (Kr) cause deletions of segments in the embryo and also affect Malpighian tubule development. In the hypomorphic Kr alleles that were analyzed, the defects in the segment pattern and the Malpighian tubules are parallel in strength. We have sequenced the DNA of four Kr alleles that show normal spatial and temporal patterns of Kr-encoded protein expression. Three of the four alleles have single base pair mutations that result in a single amino acid change. The exchanges occur in the putative DNA-binding domain of the Kr protein, which is characterized by four repeats of the zinc finger motif. Sequence comparison of the finger motifs helped to define the structural requirements for the folding of the finger domain to some extent. Our data on the Kr mutants support the view that has emerged from the evolutionary analysis.

Alleles↗
PubMed1991

Molecular evolution of inversions in Drosophila pseudoobscura: the amylase gene region.

The amylase region of the third chromosome of Drosophila pseudoobscura has been cloned and localized to cytological band 73A. It is contained within a series of highly polymorphic inversions and serves as a convenient tool for a molecular evolutionary analysis of the inverted gene arrangements. Amylase in D. pseudoobscura is a family of three genes, and some chromosomes have deletions for one or two of them. Two overlapping clones covering 26 kilobases were isolated and used as probes to survey DNA restriction map polymorphism among 28 lines, representing five of the major inversion types found in natural populations, as well as single chromosomes from the closely related species Drosophila persimilis and Drosophila miranda. Restriction-site differences are considerably greater among the various gene arrangements than among chromosomes with the same gene arrangement. Clustering the restriction map haplotypes yielded a dendrogram concordant with the phylogeny generated independently from cytogenetic considerations. The inversion polymorphism is estimated to be about 2 million years old.

Amylases↗
PubMed1992

Unification of the ferritin family of proteins.

Ferritin is the iron-storage protein of eukaryotic organisms. The nucleotide sequence encoding Azotobacter vinelandii bacterioferritin, a hemoprotein, was determined. The deduced amino acid sequence reveals a high degree of identity with Escherichia coli bacterioferritin and a striking similarity to eukaryotic ferritins. Moreover, derivation of a global alignment shows that virtually all key residues specifying the unique structural motifs of eukaryotic ferritin are conserved or conservatively substituted in the A. vinelandii sequence. The alignment suggests specific methionine residues as heme-binding ligands in bacterioferritins. The overall sequence similarity with conservation of key structural residues implies that all ferritins form a unified family of proteins. The results implicate ferritins as proteins potentially common to all aerobic organisms and as such useful in taxonomic classification, evolutionary analysis, and environmental monitoring.

Amino Acid Sequence↗
PubMed1996

Molecular characterization of the human peroxisomal branched-chain acyl-CoA oxidase: cDNA cloning, chromosomal assignment, tissue distribution, and evidence for the absence of the protein in Zellweger syndrome.

Peroxisomes in human liver contain two distinct acyl-CoA oxidases with different substrate specificities: (i) palmitoyl-CoA oxidase, oxidizing very long straight-chain fatty acids and eicosanoids, and (ii) a branched-chain acyl-CoA oxidase (hBRCACox), involved in the degradation of long branched fatty acids and bile acid intermediates. The accumulation of branched fatty acids and bile acid intermediates leads to severe mental retardation and death of the diseased children. In this study, we report the molecular characterization of the hBRCACox, a prerequisite for studying mutations in patients with a single enzyme deficiency. The composite cDNA sequence of hBRCACox, derived from overlapping clones isolated via immunoscreening and hybridization of human liver cDNA expression libraries, consisted of 2225 bases and contained an open reading frame of 2046 bases, encoding a protein of 681 amino acids with a calculated molecular mass of 76,739 Da. The C-terminal tripeptide of the protein is SKL, a known peroxisome targeting signal. Sequence comparison with the other acyl-CoA oxidases and evolutionary analysis revealed that, despite its broader substrate specificity, the hBRCACox is the human homolog of rat trihydroxycoprostanoyl-CoA oxidase (rTHCCox) and that separate gene duplication events led to the occurrence in mammals of acyl-CoA oxidases with different substrate specificities. Northern blot analysis demonstrated that--in contrast to the rTHCCox gene--the hBRCACox gene is transcribed also in extrahepatic tissues such as heart, kidney, skeletal muscle, and pancreas. The highest levels of the 2.6-kb mRNA were found in heart, followed by liver. The enzyme is encoded by a single-copy gene, which was assigned to chromosome 3p14.3 by fluorescent in situ hybridization. It was absent from livers of Zellweger patients as shown by immunoblot analysis and immunocytochemistry.

Amino Acid Sequence↗
PubMed1997

Acquisition and amplification of a testis-expressed autosomal gene, SSL, by the Drosophila Y chromosome.

The acquisition of autosomal fertility genes has been proposed to be an important process in human Y chromosome evolution. For example, the Y-linked fertility factor DAZ (Deleted in Azoospermia) appears to have arisen after the transposition and tandem amplification of the autosomal DAZH gene. The Drosophila melanogaster Y chromosome contains tandemly repeated Su(Ste) units that are thought to affect male fertility as suppressors of the homologous X-linked Stellate repeats. Here we report the detection of a testis-expressed autosomal gene, SSL [Su(Ste)-like], that appears to be an ancestor of the Y-linked Su(Ste) units. SSL encodes a casein kinase 2 (CK2) beta-subunit-like protein. Its putative ORF shares extensive (45%) homology with the genuine beta-subunit of CK2 and retains the conserved C-terminal and Glu/Asp-rich domains that are essential for CK2 holoenzyme regulation. SSL maps within region 60D1-2 of D. melanogaster and D. simulans polytene chromosomes. We present evidence that SSL was derived from the genuine betaCK2 gene by reverse transcription. This event resulted in the loss of the first three introns in the coding region of the SSL ancestor gene. Evolutionary analysis indicates that SSL has evolved under selective pressure at the translational level. Its sequence, especially in the 3' region, is much closer to the Y-linked Su(Ste) tandem repeats than to the betaCK2 gene. These results suggest that the acquisition of testis-specific autosomal genes may be important for the evolution of Drosophila as well as human Y chromosomes.

Amino Acid Sequence↗
PubMed1997

The exaptive excellence of spandrels as a term and prototype.

In 1979, Lewontin and I borrowed the architectural term "spandrel" (using the pendentives of San Marco in Venice as an example) to designate the class of forms and spaces that arise as necessary byproducts of another decision in design, and not as adaptations for direct utility in themselves. This proposal has generated a large literature featuring two critiques: (i) the terminological claim that the spandrels of San Marco are not true spandrels at all and (ii) the conceptual claim that they are adaptations and not byproducts. The features of the San Marco pendentives that we explicitly defined as spandrel-properties-their necessary number (four) and shape (roughly triangular)-are inevitable architectural byproducts, whatever the structural attributes of the pendentives themselves. The term spandrel may be extended from its particular architectural use for two-dimensional byproducts to the generality of "spaces left over," a definition that properly includes the San Marco pendentives. Evolutionary biology needs such an explicit term for features arising as byproducts, rather than adaptations, whatever their subsequent exaptive utility. The concept of biological spandrels-including the examples here given of masculinized genitalia in female hyenas, exaptive use of an umbilicus as a brooding chamber by snails, the shoulder hump of the giant Irish deer, and several key features of human mentality-anchors the critique of overreliance upon adaptive scenarios in evolutionary explanation. Causes of historical origin must always be separated from current utilities; their conflation has seriously hampered the evolutionary analysis of form in the history of life.

Journal Article↗
PubMed1997

Protein engineering reveals ancient adaptive replacements in isocitrate dehydrogenase.

Evolutionary analysis indicates that eubacterial NADP-dependent isocitrate dehydrogenases (EC 1.1.1.42) first evolved from an NAD-dependent precursor about 3.5 billion years ago. Selection in favor of utilizing NADP was probably a result of niche expansion during growth on acetate, where isocitrate dehydrogenase provides 90% of the NADPH necessary for biosynthesis. Amino acids responsible for differing coenzyme specificities were identified from x-ray crystallographic structures of Escherichia coli isocitrate dehydrogenase and the distantly related Thermus thermophilus NAD-dependent isopropylmalate dehydrogenase. Site-directed mutagenesis at sites lining the coenzyme binding pockets has been used to invert the coenzyme specificities of both enzymes. Reconstructed ancestral sequences indicate that these replacements are ancestral. Hence the adaptive history of molecular evolution is amenable to experimental investigation.

Amino Acid Sequence↗
PubMed1996

Identification of an additional member of the cytochrome c oxidase subunit VIIa family of proteins.

We report the cloning, nucleotide sequence, evolutionary analysis, and intracellular localization of SIG81, a silica-induced cDNA from mouse macrophages. The cDNA encodes a 111-amino acid protein with extensive sequence identity with members of the mammalian cytochrome c oxidase subunit VIIa (COX7a) family. A human SIG81 sequence >80% identical with the mouse cDNA was deducted from homologous sequences in the human expressed tags data base. The deduced aminoterminal region shows features common to mitochondrial targeting sequences. A phylogenetic analysis of the carboxyl-terminal domain homologous to COX7a identifies SIG81 as a divergent member of the family with an ancient origin. Southern blot analysis showed that the mouse genome contains two to three copies of the SIG81 gene. Northern blot analysis revealed that the SIG81 transcript is approximately 1 kb and expressed in every tissue tested, with higher levels of expression observed in kidney and liver. Antibodies raised against a glutathione S-transferase SIG81 fusion protein detected a 13.5-kDa protein that co-fractionates with mitochondrial localized enzymatic activity. Taken together, our data suggest that SIG81 is a novel member of the COX7a family that is constitutively expressed in mouse cells.

Amino Acid Sequence↗
PubMed2003

Determination of transmembrane topology of the Escherichia coli natural resistance-associated macrophage protein (Nramp) ortholog.

The natural resistance-associated macrophage protein (Nramp) defines a conserved family of secondary metal transporters. Molecular evolutionary analysis of the Nramp family revealed the early duplication of an ancestral eukaryotic Nramp gene, which was likely derived from a bacterial ortholog and characterized as a proton-dependent manganese transporter MntH (Makui, H., Roig, E., Cole, S. T., Helmann, J. D., Gros, P., and Cellier, M. F. (2000) Mol. Microbiol. 35, 1065-1078). Escherichia coli MntH represents a model of choice to study structure function relationship in the Nramp protein family. Here, we report E. coli MntH transmembrane topology using a combination of in silico predictions, genetic fusion with cytoplasmic and periplasmic reporters, and MntH functional assays. Constructs of the secreted form of beta-lactamase (Blam) revealed extra loops between transmembrane domains 1/2, 5/6, 7/8, and 9/10, and placed the C terminus periplasmically; chloramphenicol acetyltransferase constructs indicated cytoplasmic loops 2/3, 6/7, 8/9, and 10/11. Two intra loops for which no data were produced (N terminus, intra loop 4/5) both display composition bias supporting their deduced localization. The extra loops 5/6 and 6/7 and periplasmic exposure of the C terminus were confirmed by targeted reporter insertion. Three of them preserved MntH function as measured by a disk assay of divalent metal uptake and a fluorescence assay of divalent metal-dependent proton transport, whereas a truncated form lacking transmembrane domain 11 was inactive. These results demonstrate that EcoliA is a type III integral membrane protein with 11 transmembrane domains transporting both divalent metal ions and protons.

Amino Acid Sequence↗
PubMed2005

Hemimethylation and non-CpG methylation levels in a promoter region of human LINE-1 (L1) repeated elements.

DNA methylation within the promoter region of human LINE1 (L1) transposable elements is important for maintaining transcriptional inactivation and for inhibiting L1 transposition. Determining methylation patterns on the complementary strands of repeated sequences is difficult using standard bisulfite methylation analysis. Evolutionary changes in each repeat and the variations between cells or alleles of the same repeat lead to a heterogeneous population of sequences. Potential sequence biases can arise during analyses that are different for the converted sense and antisense strands. These problems can be avoided with hairpin-bisulfite PCR, a double-stranded PCR method in which complementary strands of individual molecules are attached by a hairpin linker ligated to genomic DNA. Using human L1 elements to study methylation of repeated sequences, (i) we distinguish valid L1 sequences from redundant and contaminant sequences by applying the powerful new method of molecular barcodes, (ii) we resolve a controversy on the level of hemimethylation of L1 sequences in fetal fibroblasts in favor of relatively little hemimethylation, (iii) we report that human L1 sequences in different cell types also have primarily concordant CpG methylation patterns on complementary strands, and (iv) we provide evidence that non-CpG cytosines within the regions analyzed are rarely methylated.

Base Sequence↗
PubMed2006

The essential vertebrate ABCE1 protein interacts with eukaryotic initiation factors.

The ABCE1 gene is a member of the ATP-binding cassette (ABC) multigene family and is composed of two nucleotide binding domains and an N-terminal Fe-S binding domain. The ABCE1 gene encodes a protein originally identified for its inhibition of ribonuclease L, a nuclease induced by interferon in mammalian cells. The protein is also required for the assembly of the HIV and SIV gag polypeptides. However, ABCE1 is one of the most highly conserved proteins and is found in one or two copies in all characterized eukaryotes and archaea. Yeast ABCE1/RLI1 is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex. We show here that the human ABCE1 protein is essential for in vitro and in vivo translation of mRNA and that it binds to eIF2alpha and eIF5. Inhibition of the Xenopus ABCE1 arrests growth at the gastrula stage of development, consistent with a block in translation. The human ABCE1 gene contains 16 introns, and the extremely high degree of amino acid identity allows the evolution of its introns to be examined throughout eukaryotes. The demonstration that ABCE1 plays a role in vertebrate translation initiation extends the known functions of this highly conserved protein. Translation is a highly regulated process important to development and pathologies such as cancer, making ABCE1 a potential target for therapeutics. The evolutionary analysis supports a model in which an ancestral eukaryote had large number of introns and that many of these introns were lost in non-vertebrate lineages.

ATP-Binding Cassette Transporters↗
PubMed1999

TT virus infection among IVDUs in south western China.

To elucidate the prevalence and clinical implications of infection with the newly described TT virus (TTV) among intravenous drug users (IVDUs) in Yunnan, southwest China, serum samples from 158 IVDUs (129 M, 29 F; mean age 26.1 +/- 5.5 years) were examined for TTV DNA by semi-nested polymerase chain reaction (PCR) using primers derived from the open reading frame (ORFI) of TTV DNA. The seroprevalence of viral markers of HIV, HBV, HCV and GB virus C/hepatitis G virus (GBV-C) infection was also examined. A molecular evolutionary analysis was performed. Thirty one (20%) of the IVDUs were positive for TTV DNA, and 34 (22%), 6 (4%), 98 (62%), 76 (48%), 136 (86%) and 65 (41%) were positive for anti-HIV, HBsAg, anti-HBs, anti-HBc, anti-HCV and GBV-C RNA, respectively. When all the subjects were classified according to TTV DNA positivity, no significant differences were observed in demographic, biochemical or virological characteristics between the 2 groups. TTV infection was in all cases associated with co-infection with 1 or more of the other aforementioned viruses. There were no significant differences in the various combinations of co-infection between TTV positive and negative groups. Phylogenetic analysis revealed that the TTV isolates obtained in the study could be grouped mainly into TTV genotype 1, and that some of the isolates belonged to subgroups other than those previously described. These results indicate that: 1) TTV infection is prevalent among IVDUs in China; 2) TTV probably has minor liver pathogenicity; and 3) new subgroups of genotype 1 and 2 exist in China.

Adult↗
PubMed1990

Evolution in bacterial plasmids and levels of selection.

Gene flow between different reproductive units such as bacterial plasmids and chromosomes presents unusual problems for evolutionary analysis. Far more than in eukaryotes, reproductive advantages at several levels of selection--genes, transposons, plasmids, cells, and clones--must be considered simultaneously to understand plasmid evolution. No level consistently prevails in conflict situations, and some reproductive units carry genes that restrain their own reproduction or survival, apparently to enhance the reproduction or survival of the higher-level reproductive units that carry them. Despite gene flow between plasmids and chromosomes, genes for certain functions show strong tendencies to occur on plasmids while others consistently occur on chromosomes. Functions generally associated with plasmids are diverse, but all are useful only in locally restricted contexts; it is argued that the selective consequences of the greater horizontal (within generation) transmission of plasmids are responsible for this pattern. The tendency for prokaryote transposons, which are also horizontally mobile, to carry genes similar to those commonly on plasmids supports this argument. The apparent trends in eukaryote plasmids and transposons to lack these same characters also accords with predictions of the local adaptation hypothesis, because genes on these genetic units are generally no more horizontally mobile than chromosomal genes. There are theoretical reasons to expect that plasmid genes tend to evolve more rapidly than chromosomal genes. "The selfish interests of genes have manifestly produced 'vehicles' in the forms of organelles, cells, individuals and yet higher units. If evolution is to predict as well as describe, then selfish interests must be understood in the framework of the constraints and opportunities generated by these 'vehicles'" (Buss, 1987, p. 182).

Bacteria↗
PubMed2004

Long-range control of gene expression: emerging mechanisms and disruption in disease.

Transcriptional control is a major mechanism for regulating gene expression. The complex machinery required to effect this control is still emerging from functional and evolutionary analysis of genomic architecture. In addition to the promoter, many other regulatory elements are required for spatiotemporally and quantitatively correct gene expression. Enhancer and repressor elements may reside in introns or up- and downstream of the transcription unit. For some genes with highly complex expression patterns--often those that function as key developmental control genes--the cis-regulatory domain can extend long distances outside the transcription unit. Some of the earliest hints of this came from disease-associated chromosomal breaks positioned well outside the relevant gene. With the availability of wide-ranging genome sequence comparisons, strong conservation of many noncoding regions became obvious. Functional studies have shown many of these conserved sites to be transcriptional regulatory elements that sometimes reside inside unrelated neighboring genes. Such sequence-conserved elements generally harbor sites for tissue-specific DNA-binding proteins. Developmentally variable chromatin conformation can control protein access to these sites and can regulate transcription. Disruption of these finely tuned mechanisms can cause disease. Some regulatory element mutations will be associated with phenotypes distinct from any identified for coding-region mutations.

Animals↗
PubMed1995

The genetic diversification of the HIV type 1 gag p17 gene in patients infected from a common source.

An evolutionary analysis was undertaken of HIV-1 gag p17 sequences taken from a small cohort of hemophilia B patients infected from a common batch of clotting factor concentrate. The sequence population found at seroconversion was highly homogeneous, suggesting that the infecting batch also contained little sequence variation. Genetic diversification was found in follow-up sequences taken approximately 3 years later and was generally found to be complex. Greater rates of synonymous to nonsynonymous substitution were observed, especially when comparing distantly related isolates, and the rate of synonymous substitution was used to estimate times of divergence for a number of isolates of HIV-1 including the origin of the subtypes A to H. The p17 region is therefore proposed as a useful marker for future epidemiological studies.

Amino Acid Sequence↗
PubMed2005

Conserved prefusion protein assembly in regulated exocytosis.

The regulated release of hormones and neurotransmitters is a fundamental process throughout the animal kingdom. The short time scale for the calcium triggering of vesicle fusion in regulated secretion suggests that the calcium sensor synaptotagmin and the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) membrane fusion machinery are well ordered before the calcium signal. To gain insight into the organization of the prefusion protein assembly in regulated exocytosis, we undertook a structural/functional study of the vesicular synaptotagmin1 and the plasma membrane SNARE proteins, which copurify from the brain in the absence of calcium. Based on an evolutionary analysis, mutagenesis screens, and a computational protein docking approach, we now provide the first testable description of the supramolecular prefusion assembly. Perturbing the determined synaptotagmin/SNARE-interacting interface in several models of regulated exocytosis altered the secretion of hormones and neurotransmitters. These mutations also disrupted the constitutive synaptotagmin/SNARE link in full agreement with our model. We conclude that the interaction of synaptotagmin with preassembled plasma membrane SNARE proteins, before the action of calcium, can provide a precisely organized "tethering" scaffold that underlies regulated secretion throughout evolution.

Amino Acid Sequence↗
PubMed2006

Integrating multi-attribute similarity networks for robust representation of the protein space.

MOTIVATION: A global view of the protein space is essential for functional and evolutionary analysis of proteins. In order to achieve this, a similarity network can be built using pairwise relationships among proteins. However, existing similarity networks employ a single similarity measure and therefore their utility depends highly on the quality of the selected measure. A more robust representation of the protein space can be realized if multiple sources of information are used. RESULTS: We propose a novel approach for analyzing multi-attribute similarity networks by combining random walks on graphs with Bayesian theory. A multi-attribute network is created by combining sequence and structure based similarity measures. For each attribute of the similarity network, one can compute a measure of affinity from a given protein to every other protein in the network using random walks. This process makes use of the implicit clustering information of the similarity network, and we show that it is superior to naive, local ranking methods. We then combine the computed affinities using a Bayesian framework. In particular, when we train a Bayesian model for automated classification of a novel protein, we achieve high classification accuracy and outperform single attribute networks. In addition, we demonstrate the effectiveness of our technique by comparison with a competing kernel-based information integration approach.

Algorithms↗
PubMed1997

Early therapy with interferon for acute hepatitis C acquired through a needlestick.

Because there is no effective neutralizing antibody or vaccine for preventing hepatitis C virus (HCV) transmission, HCV can be transmitted to health care workers through accidental needlesticks. Recently, two of our health care workers acquired HCV infection through needlestick accidents and developed acute hepatitis C. The route of transmission was confirmed by molecular evolutionary analysis with use of the E2 region of the HCV genome. After the clinical onset of acute hepatitis, the health care workers were treated with interferon (IFN) (total dose, approximately 300 megaunits). Neither individual developed chronic hepatitis. This finding raises the possibility that treatment with low-dose IFN following an accidental needlestick may be beneficial, even when it is started after the clinical onset of hepatitis.

Acute Disease↗