Molecular clock calibrations and substitution rates as a theoretical framework for systems approaches in TLRs: A perspective for drug targeting in leishmaniasis

Gene Reports ◽  
2016 ◽  
Vol 4 ◽  
pp. 74-86
Author(s):  
Bhavnita Soni ◽  
Vineetha Mandlik ◽  
Pruthvi Raj Bejugam ◽  
Shailza Singh
Keyword(s):  
Molecular Clock ◽  
Drug Targeting ◽  
Theoretical Framework ◽  
Substitution Rates ◽  
Systems Approaches

scholarly journals Synonymous Rates at the RpII215 Gene of Drosophila: Variation Among Species and Across the Coding Region

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 269-280 ◽  
Author(s):  
Ana Llopart ◽  
Montserrat Aguadé
Keyword(s):  
Rna Polymerase Ii ◽  
Molecular Clock ◽  
Constitutive Expression ◽  
Synonymous Substitution ◽  
Coding Region ◽  
Substitution Rates ◽  
Synonymous Mutations ◽  
Molecular Clock Hypothesis ◽  
Synonymous Substitution Rates ◽  
Clock Hypothesis

Abstract The region encompassing the RpII215 gene that encodes the largest component of the RNA polymerase II complex (1889 amino acids) has been sequenced in Drosophila subobscura, D. madeirensis, D. guanche, and D. pseudoobscura. Nonsynonymous divergence estimates (Ka) indicate that this gene has a very low rate of amino acid replacements. Given its low Ka and constitutive expression, synonymous substitution rates are, however, unexpectedly high. Sequence comparisons have allowed the molecular clock hypothesis to be tested. D. guanche is an insular species and it is therefore expected to have a reduced effective size relative to D. subobscura. The significantly higher rate of synonymous substitutions detected in the D. guanche lineage could be explained if synonymous mutations behave as nearly neutral. Significant departure from the molecular clock hypothesis for synonymous and nonsynonymous substitutions was detected when comparing the D. subobscura, D. pseudoobscura, and D. melanogaster lineages. Codon bias and synonymous divergence between D. subobscura and D. melanogaster were negatively correlated across the RpII215 coding region, which indicates that selection coefficients for synonymous mutations vary across the gene. The C-terminal domain (CTD) of the RpII215 protein is structurally and functionally differentiated from the rest of the protein. Synonymous substitution rates were significantly different in both regions, which strongly indicates that synonymous mutations in the CTD and in the non-CTD regions are under detectably different selection coefficients.

scholarly journals Variation in the molecular clock of primates

2016 ◽  
Author(s):  
Priya Moorjani ◽  
Carlos Eduardo G. Amorim ◽  
Peter F. Arndt ◽  
Molly Przeworski
Keyword(s):  
Gene Conversion ◽  
Molecular Clock ◽  
Primate Evolution ◽  
Primate Species ◽  
Recent Common Ancestor ◽  
New World Monkeys ◽  
Substitution Rates ◽  
Cpg Sites ◽  
Most Recent Common Ancestor ◽  
Biased Gene Conversion

Events in primate evolution are often dated by assuming a "molecular clock", i.e., a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life-history traits, suggesting that it should also be found among primates. Motivated by these considerations, we analyze whole genomes from ten primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs) and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are ~65% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ~2% higher in chimpanzees and ~7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however: in particular, transitions at CpG sites exhibit a more clock-like behavior than do other types, presumably due to their non-replicative origin. Thus, not only the total rate, but also the mutational spectrum varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate that the average time to the most recent common ancestor of human and chimpanzee is 12.1 million years and their split time 7.9 million years.

scholarly journals High rate of viral evolution in the capsid protein of porcine parvovirus

2011 ◽  
Vol 92 (11) ◽  
pp. 2628-2636 ◽  
Author(s):  
André Felipe Streck ◽  
Sandro Luis Bonatto ◽  
Timo Homeier ◽  
Carine Kunzler Souza ◽  
Karla Rathje Gonçalves ◽  
...  
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Molecular Clock ◽  
Nucleotide Substitution ◽  
Protein Gene ◽  
Rna Viruses ◽  
Porcine Parvovirus ◽  
Nucleotide Substitution Rate ◽  
Substitution Rates ◽  
Field Isolates

In recent years, it has been shown that some parvoviruses exhibit high substitution rates, close to those of RNA viruses. In order to monitor and determine new mutations in porcine parvovirus (PPV), recent PPV field isolates from Austria, Brazil, Germany and Switzerland were sequenced and analysed. These samples, together with sequences retrieved from GenBank, were included in three datasets, consisting of the complete NS1 and VP1 genes and a partial VP1 gene. For each dataset, the nucleotide substitution rate and the molecular clock were determined. Analysis of the PPV field isolates revealed that a recently described amino acid substitution, S436T, appeared to be common in the VP2 protein in the Austrian, Brazilian and German virus populations. Furthermore, new amino acid substitutions were identified, located mainly in the viral capsid loops. By inferring the evolutionary dynamics of the PPV sequences, nucleotide substitution rates of approximately 10−5 substitutions per site per year for the non-structural protein gene and 10−4 substitutions per site per year for the capsid protein gene (for both viral protein datasets) were found. The latter rate is similar to those commonly found in RNA viruses. An association of the phylogenetic tree with the molecular clock analysis revealed that the mutations on which the divergence for both capsid proteins was based occurred in the past 30 years. Based on these findings, it was concluded that PPV variants are continuously evolving and that vaccines, which are based mainly on strains isolated about 30 years ago, should perhaps be updated.

scholarly journals Life history effects on the molecular clock of autosomes and sex chromosomes

2016 ◽  
Vol 113 (6) ◽  
pp. 1588-1593 ◽  
Author(s):  
Guy Amster ◽  
Guy Sella
Keyword(s):  
Molecular Clock ◽  
Generation Time ◽  
Life Histories ◽  
Age Of Onset ◽  
Mutation Rates ◽  
Major Influence ◽  
Molecular Evidence ◽  
Substitution Rates ◽  
History Effects ◽  
Low X

One of the foundational results in molecular evolution is that the rate at which neutral substitutions accumulate on a lineage equals the rate at which mutations arise. Traits that affect rates of mutation therefore also affect the phylogenetic “molecular clock.” We consider the effects of sex-specific generation times and mutation rates in species with two sexes. In particular, we focus on the effects that the age of onset of male puberty and rates of spermatogenesis have likely had in hominids (great apes), considering a model that approximates features of the mutational process in mammals, birds, and some other vertebrates. As we show, this model can account for a number of seemingly disparate observations: notably, the puzzlingly low X-to-autosome ratios of substitution rates in humans and chimpanzees and differences in rates of autosomal substitutions among hominine lineages (i.e., humans, chimpanzees, and gorillas). The model further suggests how to translate pedigree-based estimates of human mutation rates into split times among extant hominoids (apes), given sex-specific life histories. In so doing, it largely bridges the gap reported between estimates of split times based on fossil and molecular evidence, in particular suggesting that the human–chimpanzee split may have occurred as recently as 6.6 Mya. The model also implies that the “generation time effect” should be stronger in short-lived species, explaining why the generation time has a major influence on yearly substitution rates in mammals but only a subtle one in human pedigrees.

Calibration of a molecular clock in tits (Paridae)—Do nucleotide substitution rates of mitochondrial genes deviate from the 2% rule?

2007 ◽  
Vol 44 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Martin Päckert ◽  
Jochen Martens ◽  
Dieter Thomas Tietze ◽  
Christian Dietzen ◽  
Michael Wink ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Nucleotide Substitution ◽  
Mitochondrial Genes ◽  
Substitution Rates ◽  
Nucleotide Substitution Rates

scholarly journals Estimating the variability of substitution rates.

Genetics ◽  
1989 ◽  
Vol 123 (3) ◽  
pp. 615-619 ◽  
Author(s):  
M Bulmer
Keyword(s):  
Amino Acid ◽  
Molecular Clock ◽  
Common Ancestor ◽  
Standard Errors ◽  
Homologous Gene ◽  
Substitution Rates ◽  
Nucleotide Data ◽  
Substantial Bias ◽  
Best Estimates

Abstract Suppose that amino acid or nucleotide data are available for a homologous gene in several species which diverged from a common ancestor at about the same time and that substitution rates between all pairs of species are calculated, correcting as necessary for multiple substitutions and for back and parallel substitutions. The variances and covariances of these corrected substitution rates are evaluated, and are used to construct a new test for uniformity (constancy of the molecular clock) and to find the best estimates of substitution rates in individual lineages with their standard errors. A substantial bias may arise if the effect of correcting the pairwise substitution rates is ignored.

scholarly journals Response to Comment on “The Placental Mammal Ancestor and the Post–K-Pg Radiation of Placentals”

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 613.3-613 ◽  
Author(s):  
Maureen A. O’Leary ◽  
Jonathan I. Bloch ◽  
John J. Flynn ◽  
Timothy J. Gaudin ◽  
Andres Giallombardo ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Explanatory Power ◽  
Placental Mammal ◽  
Substitution Rates ◽  
Power Application ◽  
Tree Building ◽  
Diverse Data ◽  
Clock Models

Tree-building with diverse data maximizes explanatory power. Application of molecular clock models to ancient speciation events risks a bias against detection of fast radiations subsequent to the Cretaceous-Paleogene (K-Pg) event. Contrary to Springer et al., post–K-Pg placental diversification does not require “virus-like” substitution rates. Even constraining clade ages to their model, the explosive model best explains placental evolution.

Estimating divergence times of notothenioid fishes using a fossil-calibrated molecular clock

2004 ◽  
Vol 16 (1) ◽  
pp. 37-44 ◽  
Author(s):  
THOMAS J. NEAR
Keyword(s):  
Maximum Likelihood ◽  
Molecular Clock ◽  
Nucleotide Substitution ◽  
Divergence Time ◽  
Divergence Times ◽  
Substitution Rates ◽  
Cold Adapted ◽  
Divergence Time Estimates ◽  
Time Estimates ◽  
Nucleotide Substitution Rates

Hypotheses concerning the diversification of notothenioid fishes have relied extensively on estimates of divergence times using molecular clock methods. The timing of diversification of the cold adapted antifreeze glycoprotein (AFGP)-bearing Antarctic notothenioid clade in the middle to late Miocene has been correlated with the onset of polar climatic conditions along the Antarctic Continental Shelf. Critical examination of the previous molecular clock analyses of notothenioids reveals several problems associated with heterogeneity of nucleotide substitution rates among lineages, the application of potentially inappropriate nucleotide substitution rates, and the lack of confidence intervals for divergence time estimates. In this study, the notothenioid partial gene mtDNA 12S-16S rRNA (PG-rRNA) molecular clock was reanalysed using a tree-based maximum likelihood strategy that attempts to account for rate heterogeneity of nucleotide substitution rates among lineages using the penalized likelihood method, and bootstrap resampling to estimate confidence intervals of divergence time estimates. The molecular clock was calibrated using the notothenioid fossil Proeleginops grandeastmanorum. Divergence time estimates for all nodes in the PG-rRNA maximum likelihood tree were substantially older than previous estimates. In particular, the estimated age of the AFGP-bearing Antarctic notothenioid clade predates the onset of extensive sea ice and development of polar conditions by at least 10 million years. Despite caveats involving the fossil calibration and limitations of the PG-rRNA dataset, these divergence time estimates provide initial observations for the development of a novel model of the diversification of cold adapted Antarctic notothenioid fishes.

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