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Results for “molecular clock”

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At least 145 records · Page 8Linked to original sources
PubMed1999

Molecular clock and recombination in primate Mhc genes.

To set an accurate chronological framework to the evolution of primate class I and II genes in the major histocompatibility complex (Mhc), the rate of silent nucleotide substitutions in exons and introns is examined for various cDNA and genome sequences currently available. The rate is sensitive to the GC content and correlates negatively with increased GC biases at the third codon positions of Mhc genes. The intergenic recombination rate in the HLA region is estimated from the synonymous nucleotide differences at 37 linked loci. Any HLA subregion is recombined more or less at the ordinary rate of 1 cM per 1 Mb, although the rate may be reduced in some subregions. This information is used to discuss HLA haplotypes when they are applied to studies of human demography. The unusual polymorphism in the alpha-helix of HLA-DRB1 is also revisited in relation to intragenic recombination, but the molecular mechanism and the evolutionary cause both remain enigmatic.

Animals↗
PubMed1997

Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis.

We have identified and characterized c-hairy1, an avian homolog of the Drosophila segmentation gene, hairy. c-hairy1 is strongly expressed in the presomitic mesoderm, where its mRNA exhibits cyclic waves of expression whose temporal periodicity corresponds to the formation time of one somite (90 min). The apparent movement of these waves is due to coordinated pulses of c-hairy1 expression, not to cell displacement along the anteroposterior axis, nor to propagation of an activating signal. Rather, the rhythmic c-hairy mRNA expression is an autonomous property of the paraxial mesoderm. These results provide molecular evidence for a developmental clock linked to segmentation and somitogenesis of the paraxial mesoderm, and support the possibility that segmentation mechanisms used by invertebrates and vertebrates have been conserved.

Animals↗
PubMed2001

On the dispersion index of a Markovian molecular clock.

The number of nucleotide substitutions accumulated in a gene or in a lineage is an important random variable in the study of molecular evolution. Of particular interest is the ratio of the variance to the mean of that random variable, often known as the dispersion index. Because nucleotide substitution is most commonly modeled by a continuous-time four-state Markov chain, this paper provides a systematic method of computing the dispersion indices exhibited by a continuous-time four-state Markov chain. Using this method along with computer algebra and Monte Carlo simulation, this paper offers partially proven conjectures that were supported by thorough computer experiments. It is believed that the Tamura model, the equal-input model and the Takahata-Kimura model always exhibit dispersion indices less than 2. It is also believed that a general four-state model can be chosen to exhibit a dispersion index of any desired magnitude, although the chance of a randomly chosen such model exhibiting a dispersion index greater than 2 is as small as about 2%. Relevance of these findings to the neutral theory is discussed.

Computer Simulation↗
PubMed2004

Expression of the gene for Dec2, a basic helix-loop-helix transcription factor, is regulated by a molecular clock system.

Dec2, a member of the basic helix-loop-helix superfamily, is a recently confirmed regulatory protein for the clockwork system. Transcripts of Dec2, as well as those of its related gene Dec1, exhibit a striking circadian oscillation in the suprachiasmatic nucleus, and Dec2 inhibits transcription from the Per1 promoter induced by Clock/Bmal1 [Honma, Kawamoto, Takagi, Fujimoto, Sato, Noshiro, Kato and Honma (2002) Nature (London) 419, 841-844]. It is known that mammalian circadian rhythms are controlled by molecular clockwork systems based on negative-feedback loop(s), but the molecular mechanisms for the circadian regulation of Dec2 gene expression have not been clarified. We show here that transcription of the Dec2 gene is regulated by several clock molecules and a negative-feedback loop. Luciferase and gel retardation assays showed that expression of Dec2 was negatively regulated by binding of Dec2 or Dec1 to two CACGTG E-boxes in the Dec2 promoter. Forced expression of Clock/Bmal1 and Clock/Bmal2 markedly increased Dec2 mRNA levels, and up-regulated the transcription of the Dec2 gene through the CACGTG E-boxes. Like Dec, Cry and Per also suppressed Clock/Bmal-induced transcription from the Dec2 promoter. Moreover, the circadian expression of Dec2 transcripts was abolished in the kidney of Clock/Clock mutant mice. These findings suggest that the Clock/Bmal heterodimer enhances Dec2 transcription via the CACGTG E-boxes, whereas the induced transcription is suppressed by Dec2, which therefore must contribute to its own rhythmic expression. In addition, Cry and Per may also modulate Dec2 transcription.

5' Flanking Region↗
PubMed2006

The type III flagellar export specificity switch is dependent on FliK ruler and a molecular clock.

Salmonella flagellar hook length is controlled at the level of export substrate specificity of the FlhB component of the type III flagellar export apparatus. FliK is believed to be the hook length sensor and interacts with FlhB to change its export specificity upon hook completion. To find properties of FliK expected of such a molecular ruler, we assayed binding of FliK to the hook and found that the N-terminal domain of FliK (FliK(N)) bound to the hook-capping protein FlgD with high affinity and to the hook protein FlgE with low affinity. To investigate a possible role of FlgE in hook length control, flgE mutants with partially impaired motility were isolated and analyzed. Eight flgE mutants obtained all formed flagellar filaments. The mutants produced significantly shorter hooks while the hook-type substrates such as FlgE, FliK and FlgD were secreted in large amounts, suggesting defective hook assembly with the mutant FlgE proteins. Upon overexpression, mutant FlgEs produced hooks of normal length and wild-type FlgE produced longer hooks. These results suggest that hook length is dependent on the hook polymerization rate and that the start of hook polymerization initiates a "time countdown" for the specificity switch to occur or for significant slow down of rod/hook-type export after hook length reaches around 55 nm for later infrequent FliK(C)-FlhB(C) interaction. We propose that FliK(N) acts as a flexible tape measure, but that hook length is also dependent on the hook elongation rate and a switch timing mechanism.

Bacterial Proteins↗
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↗
PubMed2001

Molecular clocks.

A convenient and precise mass spectrometric method for measurement of the deamidation rates of glutaminyl and asparaginyl residues in peptides and proteins has been developed; the rates of deamidation of 306 asparaginyl sequences in model peptides at pH 7.4, 37.0 degrees C, 0.15 M Tris.HCl buffer have been determined; a library of 913 amide-containing peptides for use by other investigators in similar studies has been established; and, by means of simultaneous deamidation rate measurements of rabbit muscle aldolase and appropriate model peptides in the same solutions, the use of this method for quantitative measurement of the relative effects of primary, secondary, tertiary, and quaternary protein structure on deamidation rates has been demonstrated. The measured rates are discussed with respect to the hypothesis that glutaminyl and asparaginyl residues serve, through deamidation, as molecular timers of biological events.

Amides↗
PubMed2004

Genome-wide molecular clock and horizontal gene transfer in bacterial evolution.

We describe a simple theoretical framework for identifying orthologous sets of genes that deviate from a clock-like model of evolution. The approach used is based on comparing the evolutionary distances within a set of orthologs to a standard intergenomic distance, which was defined as the median of the distribution of the distances between all one-to-one orthologs. Under the clock-like model, the points on a plot of intergenic distances versus intergenomic distances are expected to fit a straight line. A statistical technique to identify significant deviations from the clock-like behavior is described. For several hundred analyzed orthologous sets representing three well-defined bacterial lineages, the alpha-Proteobacteria, the gamma-Proteobacteria, and the Bacillus-Clostridium group, the clock-like null hypothesis could not be rejected for approximately 70% of the sets, whereas the rest showed substantial anomalies. Subsequent detailed phylogenetic analysis of the genes with the strongest deviations indicated that over one-half of these genes probably underwent a distinct form of horizontal gene transfer, xenologous gene displacement, in which a gene is displaced by an ortholog from a different lineage. The remaining deviations from the clock-like model could be explained by lineage-specific acceleration of evolution. The results indicate that although xenologous gene displacement is a major force in bacterial evolution, a significant majority of orthologous gene sets in three major bacterial lineages evolved in accordance with the clock-like model. The approach described here allows rapid detection of deviations from this mode of evolution on the genome scale.

Evolution, Molecular↗