Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “molecular evolution”

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 235 records · Page 13Linked to original sources
PubMed2006

Molecular evolution of adrenoceptors and dopamine receptors: implications for the binding of catecholamines.

We derived homology models for all human catecholamine-binding GPCRs (CABRs; the alpha-1, alpha-2, and beta-adrenoceptors and the D1-type and D2-type dopamine receptor) using the bovine rhodopsin-11-cis-retinal X-ray structure. Interactions were predicted from the endogenous ligands norepinephrine or dopamine and from the binding site and were used to optimize receptor-ligand interactions. Similar binding modes in the complexes agree with a large "binding core" conserved across the CABRs, that is, D3.32, V(I)3.33, T3.37, S5.42, S(A/C)5.43, S5.46, F6.51, F6.52, and W6.48. Model structures and docking simulations suggest that extracellular loop 2 could provide a common attachment point for the ligands' beta-hydroxyl via a hydrogen bond donated by the main-chain NH group of residue xl2.52. The modeled CABRs and docking modes are in good agreement with published experimental studies. Complementarity between the ligand and the binding site suggests that the bovine rhodopsin structure is a suitable template for modeling agonist-bound CABRs.

Adrenergic Agonists↗
PubMed1998

Molecular evolution of cdc2 pseudogenes in spruce (Picea).

The p34cdc2 protein and other cyclin-dependent protein kinases (CDK) are important regulators of eukaryotic cell cycle progression. We have previously cloned a functional cdc2 gene from Picea abies and found it to be part of a family of related sequences, largely consisting of pseudogenes. We now report on the isolation of partial cdc2 pseudogenes from Picea engelmannii and Picea sitchensis, as well as partial functional cdc2 sequences from P. engelmannii, P. sitchensis and Pinus contorta. A high level of conservation between species was detected for these sequences. Phylogenetic analyses of pseudogene and functional cdc2 sequences, as well as the presence of shared insertions or deletions, support the division of most of the cdc2 pseudogenes into two subfamilies. New cdc2 pseudogenes appear to have been formed in Picea at a much higher rate than they have been obliterated by neutral mutations. The pattern of nucleotide changes in the cdc2 pseudogenes, as compared to a presumed ancestral functional cdc2 gene, was similar to that previously found in mammalian pseudogenes, with a strong bias for the transitions C to T and G to A, and the transversions C to A and G to T.

Amino Acid Sequence↗
PubMed1998

Molecular evolution of viruses--Past and Present, Part 2--An introduction.

The evolution of viruses is reviewed within the perspective of the concepts on the evolution of the lipid membrane bound vesicular structures in the prebiotic soup through the ideas on evolution of cells during the RNA World and the transition into the DNA World. The ancient Archeae bacteria and their retrons that carry the bacterial reverse transcriptase gene and their unique protein splicing capability provide an indication of the evolutionary path for retroviruses and, independently, for RNA and DNA viruses of the prokaryotic Archeae bacteria and the eukaryotic yeast and fungi.

Archaea↗
PubMed2001

The reactions of methanimine and cyanogen with carbon monoxide in prebiotic molecular evolution on earth.

A primeval atmosphere is proposed containing simple molecules such as formaldehyde, ammonia, carbon monoxide, cyanogen and hydrogen cyanide, which have been detected in space. Chemical reactions are described for the formation of aziridine-2-one and di-azirine-3-one derivatives as potential precursors for the original synthesis of amino-acids, proteins, pyrimidines, purines, nicotinamide and flavin. The reactions have been shown to be kinetically feasible from the overall enthalpy changes in the ZKE approximation at the MP2/6-31G* level.

Carbon Monoxide↗
PubMed2003

Molecular evolution of nucleoside diphosphate kinase genes: conserved core structures and multiple-layered regulatory regions.

Genomic data regarding the nucleoside diphosphate (NDP) kinase genes have been accumulated from diverged phyla. Comparison of their regulatory sequences have shed light on the multiple facets of gene regulation systems. Phylogenetic studies, including CpG island and intron-mapping, and homologous sequence comparison, have suggested that the regions of the major mammalian genes, the ortholog (rat alpha or nm23-H2) and its paralog (rat beta or nm23-H1), have been constructed by a stepwise gain and loss of alien genes resulting in "multiple-layered" regulatory systems. They contain representative cis-elements for the constitutive, stage/lineage-specific, and early response expression. These elements' binding capacities to nuclear proteins were confirmed by electrophoretic mobility shift assay. Further, these regulatory systems generate heterogeneous mRNA at the 5' untranslated region, which influences their own translation efficiencies. In terms of this process, the transcription system would control another layer of gene expression: posttranscriptional (translational) regulation.

Amino Acid Sequence↗
PubMed2000

Molecular evolution and intratumor heterogeneity by topographic compartments in muscle-invasive transitional cell carcinoma of the urinary bladder.

Superficial transitional cell carcinomas (TCC) of the urinary bladder have been shown to be monoclonal. However, no combined study of clonality and tumor suppressor genes (TSG) is available to date for muscle-invasive TCC. Forty-four muscle-invasive TCC of the urinary bladder selected from women were included in this study. Tumor cells located above and below the muscularis mucosa zone were systematically microdissected and used for DNA extraction. Hha-I digested and undigested samples were used to study the methylation pattern of androgen receptor alleles and undigested samples were used for microsatellite analysis of TSG (TP53, RB1, WT1, and NF1). Both loss of heterozygosity (LOH) and single nucleotide polymorphism (SNP) analyses were performed using optimized denaturing gradient gel electrophoresis. The expression of p53, pRB, and p21WAF1 was assessed by immunohistochemistry. Appropriate controls were run in every case. All except two TCC showed a monoclonal pattern with the same allele inactivated in both compartments. Microsatellite analysis of TSG revealed the same LOH/SNP pattern in both tumor compartments in 30 cases (involving more than 1 TSG locus in 8) and genetic heterogeneity in 14 cases. From the latter group, 9 cases expressed more genetic changes in the deep compartment (involving TP53 gene in all cases, WT1 gene in 2, and NF1 in 1), whereas in 4 cases the superficial compartment showed more genetic changes (three involving NF1 and one involving both RB and TP53). No statistical difference in the immunoexpression was detected, although it tended to be higher in the superficial compartment than in the deep compartment. These concordant data in polymorphic DNA regions indicate that bladder-muscle-invasive TCC are monoclonal proliferations with homogeneous tumor cell selection. Heterogeneous tumor cell selection by topography defined two different genetic compartments: superficial, NF1-defective, and deep, TP53-defective. No differences in the immunohistochemical expression were observed, precluding a more extensive clinical application.

Base Sequence↗
PubMed1998

Molecular evolution by staggered extension process (StEP) in vitro recombination.

We have developed a simple and efficient method for in vitro mutagenesis and recombination of polynucleotide sequences. The staggered extension process (StEP) consists of priming the template sequence(s) followed by repeated cycles of denaturation and extremely abbreviated annealing/polymerase-catalyzed extension. In each cycle the growing fragments anneal to different templates based on sequence complementarity and extend further. This is repeated until full-length sequences form. Due to template switching, most of the polynucleotides contain sequence information from different parental sequences. The method is demonstrated by the recombination of two genes encoding thermostable subtilisins carrying two phenotypic markers separated by 113 base pairs and eight other point mutation markers. To demonstrate its utility for directed evolution, we have used StEP to recombine a set of five thermostabilized subtilisin E variants identified during a single round of error-prone PCR mutagenesis and screening. Screening the StEP-recombined library yielded an enzyme whose half-life at 65 degrees C is 50 times that of wild-type subtilisin E.

Bacillus subtilis↗
PubMed1997

Molecular evolution of an arsenate detoxification pathway by DNA shuffling.

Functional evolution of an arsenic resistance operon has been accomplished by DNA shuffling, involving multiple rounds of in vitro recombination and mutation of a pool of related sequences, followed by selection for increased resistance in vivo. Homologous recombination is achieved by random fragmentation of the PCR templates and reassembly by primerless PCR. Plasmid-determined arsenate resistance from plasmid pl258 encoded by genes arsR, arsB, and arsC was evolved in Escherichia coli. Three rounds of shuffling and selection resulted in cells that grew in up to 0.5 M arsenate, a 40-fold increase in resistance. Whereas the native plasmid remained episomal, the evolved operon reproducibly integrated into the bacterial chromosome. In the absence of shuffling, no increase in resistance was observed after four selection cycles, and the control plasmid remained episomal. The integrated ars operon had 13 mutations. Ten mutations were located in arsB, encoding the arsenite membrane pump, resulting in a fourfold to sixfold increase in arsenite resistance. While arsC, the arsenate reductase gene, contained no mutations, its expression level was increased, and the rate of arsenate reduction was increased 12-fold. These results show that DNA shuffling can improve the function of pathways by complex and unexpected mutational mechanisms that may be activated by point mutation. These mechanisms may be difficult to explain and are likely to be overlooked by rational design.

Adenosine Triphosphatases↗
PubMed1998

Man-made cell-like compartments for molecular evolution.

Cellular compartmentalization is vital for the evolution of all living organisms. Cells keep together the genes, the RNAs and proteins that they encode, and the products of their activities, thus linking genotype to phenotype. We have reproduced this linkage in the test tube by transcribing and translating single genes in the aqueous compartments of water-in-oil emulsions. These compartments, with volumes close to those of bacteria, can be recruited to select genes encoding catalysts. A protein or RNA with a desired catalytic activity converts a substrate attached to the gene that encodes it to product. In other compartments, substrates attached to genes that do not encode catalysts remain unmodified. Subsequently, genes encoding catalysts are selectively enriched by virtue of their linkage to the product. We demonstrate the linkage of genotype to phenotype in man-made compartments using a model system. A selection for target-specific DNA methylation was based on the resistance of the product (methylated DNA) to restriction digestion. Genes encoding HaeIII methyltransferase were selected from a 10(7)-fold excess of genes encoding another enzyme.

Base Sequence↗
PubMed2006

Bottlenecks and broomsticks: the molecular evolution of Mycobacterium bovis.

Mycobacterium bovis is the cause of tuberculosis in cattle and is a member of the Mycobacterium tuberculosis complex. In contrast to many other pathogenic bacterial species, there is little evidence for the transfer and recombination of genes between cells. The clonality of this group of organisms indicates that the population structure is dominated by reductions in diversity, caused either by population bottlenecks or selective sweeps as entire chromosomes become fixed in the population. We describe how these forces have shaped not only the phylogeny of this group but also, at a very local level, the population structure of Mycobacterium bovis in the British Isles. We also discuss the practical implications of applying this knowledge to understanding the spread of infection and the development of improved vaccines and diagnostic tests.

Animals↗
PubMed2005

Molecular evolution of the rice miR395 gene family.

MicroRNAs (miRNAs) are 20-22 nucleotide non-coding RNAs that play important roles in plant and animal development. They are usually processed from larger precursors that can form stem-loop structures. Among 20 miRNA families that are conserved between Arabidopsis and rice, the rice miR395 gene family was unique because it was organized into compact clusters that could be transcribed as one single transcript. We show here that in fact this family had four clusters of total 24 genes. Three of these clusters were segmental duplications. They contained miR395 genes of both 120 bp and 66 bp long. However, only the latter was repeatedly duplicated. The fourth cluster contained miR395 genes of two different sizes that could be the consequences of intergenic recombination of genes from the first three clusters. On each cluster, both 1-duplication and 2-duplication histories were observed based on the sequence similarity between miR395 genes, some of which were nearly identical suggesting a recent origin. This was supported by a miR395 locus survey among several species of the genus Oryza, where two clusters were only found in species with an AA genome, the genome of the cultivated rice. A comparative study of the genomic organization of Medicago truncatula miR395 gene family showed significant expansion of intergenic spaces indicating that the originally clustered genes were drifting away from each other. The diverse genomic organizations of a conserved microRNA gene family in different plant genomes indicated that this important negative gene regulation system has undergone dramatic tune-ups in plant genomes.

Base Sequence↗
PubMed1999

Selective pressure as an essential force in molecular evolution of myeloid leukemic clones: a view from the window of Fanconi anemia.

Specific chromosomal deletions are commonly found in bone marrow cells of children with Fanconi anemia (FA) whose disease has evolved to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Identical deletions are found in adults with MDS/AML with a history of exposure to alkylating agents (secondary MDS/AML). While deleted chromosomal regions likely harbor genes encoding proteins with tumor suppressor (TS) function, such genes have not been identified and the environmental forces by which these mutant clones are selected remain unclear. A consistent signaling abnormality in cells bearing mutations of the Fanconi anemia complementation group C (FA-C) gene (FANCC) has revealed a potential selective force. Hematopoietic progenitor cells from patients and mice with FANCC mutations are hypersensitive to the inhibitory effects of IFNgamma and TNFalpha. Consequently, clonal outgrowths in FA likely result from strong selective pressure for stem and/or progenitor cells resistant to these inhibitory cytokines. Additional mutations that inactivate signaling pathways for these inhibitors would create a cell with a profound proliferative advantage over its apoptosis-prone counterparts. Here, we present preliminary evidence supporting a selection-based model of leukemic evolution and argue that MDS in FA patients is a de facto model of secondary MDS in non-FA adults.

Acute Disease↗