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Main conclusion: This study compared the plastomes of Ulmaceae allowing analyses of the dynamic evolution, including genome structure, codon usage bias, repeat sequences, molecular mutation rates, and phylogenetic inferences. Ulmaceae is a small family in the order Rosales. This family consists of seven genera, including Ulmus, Zelkova, Planera, Hemiptelea, Phyllostylon, Ampelocera, and Holoptelea. Ulmaceae is an interesting lineage from plant biogeographic, systematic, evolutionary, and paleobotanic perspectives. It is also a good model to investigate the evolution of the plastomes in woody plants. In this study, we sequenced and assembled the complete plastomes of the six Ulmaceae genera to compare genomic structures and reveal the molecular evolutionary patterns. The size of the quadripartite plastomes ranged from 158,290 bp to 161,886 bp. The genomes contained 131 genes, including 87 coding genes, 36 tRNA, and 8 rRNA. The gene number, gene content, and genomic structure were highly consistent among the Ulmaceae genera. Nine variable regions including ndhA intron, ndhF-rpl32, ycf1, psbK-trnS,rps16-trnQ, trnT-trnL, trnT-psbD, trnS-trnG, and rpl32-trnL, were identified in Ulmaceae plastomes according to the nucleotide diversity values. Condon usage was biased among the genes and showed consistent trends in the seven genera. Molecular evolution analyses revealed that most of the genes and all gene groups were under widespread purifying selection. Twelve genes (ccsA, matK, psbH, psbK, rbcL, rpl22, rpl32, rpoA, rps12, rps15, rps16, and ycf2) were under positive selection. Phylogenetic analyses supported that Ulmaceae should be divided into two main clades, such as the temperate clade, including Ulmus, Zelkova, Planera, and Hemiptelea and the tropical clade, including Phyllostylon, Ampelocera and Holoptelea. This study reports the structure and evolutionary characteristics of the Elm family. These new genomic data will benefit assessments of genomic evolution and provide information to elucidate the phylogenetic relationships among Ulmaceae species. [ABSTRACT FROM AUTHOR]

The evolution of bacterial endosymbiont genomes is strongly influenced by host-driven selection. Factors affecting host genome evolution will potentially affect endosymbiont genomes in similar ways. One potential outcome is correlations in molecular rates between the genomes of the symbiotic partners. Recently, we presented the first evidence of such correlations between the mitochondrial genomes of cockroaches and the genomes of their endosymbiont (Blattabacterium cuenoti). Here we investigate whether similar patterns are found in additional host-symbiont partners. We use partial genome data from multiple strains of the bacterial endosymbionts Buchnera aphidicola and Sulcia muelleri, and the mitochondrial genomes of their sap-feeding insect hosts. Both endosymbionts show phylogenetic congruence with the mitochondria of their hosts, a result that is expected due to their identical mode of inheritance. We compared root-to-tip distances and branch lengths of phylogenetically independent species pairs. Both analyses showed a highly significant correlation of molecular rates between the genomes of Buchnera and the mitochondrial genomes of their hosts. A similar correlation was detected between Sulcia and their hosts, but was not statistically significant. Our results indicate that evolutionary rate correlations between hosts and long-term symbionts may be a widespread phenomenon. [ABSTRACT FROM AUTHOR]

Energy structure in global terminal consumption is moving towards a direction of low carbon. This study analyzes the evolution of the share of coal in energy consumption structure by continuous dynamical systems. Based on the complex and dynamic interactions among energy sources, an n-dimensional dynamical system model is constructed where the alternative of other energy sources for coal are modeled by the linear parameters. A case study of China is performed on its terminal energy consumption structure. Three scenarios are set to analyze and compare the particular evolution paths of coal share: the substitution rate changes, the self-growth rate changes, and both the substitution rate and self-growth rate change. Results show that the improvement of renewable power in either the substitution rate or self-growth rate is the most effective to reduce the proportion of coal. As to other energy sources, raising the coal substitution rate is better than increasing their self-growth rate. It concludes that proper control of coal power, moderate development of hydropower, and active and safe development of nuclear power are likely increase the proportion of electric in terminal energy consumption. This study provides an alternative and promising approach to analyze the evolution of coal ratio in energy consumption structure and may have potential application in other areas and countries. [ABSTRACT FROM AUTHOR]

Main conclusion: Bignoniaceae species have conserved chloroplast structure, with hotspots of nucleotide diversity. Several genes are under positive selection, and can be targets for evolutionary studies. Bignoniaceae is one of the most species-rich family of woody plants in Neotropical seasonally dry forests. Here we report the assembly of Handroanthus impetiginosus chloroplast genome and evolutionary comparative analyses of ten Bignoniaceae species representing the genera for which whole-genome chloroplast sequences were available. The chloroplast genome of H. impetiginosus is 159,462 bp in size and has a similar structure compared to the other nine species. The total number of genes was slightly variable amongst the Bignoniaceae, ranging from 124 in H. impetiginosus to 144 in Anemopaegma acutifolium. The inverted repeat (IR) size was variable, ranging from 24,657 bp (Tecomaria capensis) to 40,481 bp (A. acutifolium), due to the contraction and retraction at its boundaries. However, gene boundaries were very similar among the ten species. We found 98 forward and palindromic dispersed repeats, and 85 simple sequence repeats (SSRs). In general, chloroplast sequences were highly conserved, with few nucleotide diversity hotspots in the genes accD, clpP, rpoA, ycf1, ycf2. The phylogenetic analysis based on 77 coding genes was highly consistent with Angiosperm Phylogeny Group (APG) IV. Our results also indicate that most genes are under negative selection or neutral evolution. We found no evidence of branch-site selection, implying that H. impetiginosus is not evolving faster than the other species analyzed, notwithstanding we found site positive selection signal in several genes. These genes can provide targets for evolutionary studies in Bignoniaceae and Lamiales species. [ABSTRACT FROM AUTHOR]

The family Vitaceae includes the domesticated grapevine (Vitis vinifera), one of the most economically important crops in the world. Despite the importance of Vitaceae, there is still considerable controversy surrounding their phylogenetic relationships and evolutionary timescales. Moreover, variation in rates of molecular evolution among Vitaceae remains mostly unexplored. The present research aims to fill these knowledge gaps through the analysis of plastome sequences. Thirteen newly sequenced grape plastomes are presented and their phylogenetic relationships examined. Divergence times and absolute substitution rates are inferred under different molecular clocks by the analysis of 95 non-coding plastid regions and 43 representative accessions of the major lineages of Vitaceae. Furthermore, the phylogenetic informativeness of non-coding plastid regions is investigated. We find strong evidence in favor of the random local clock model and rate heterogeneity within Vitaceae. Substitution rates decelerate in Ampelocissus, Ampelopsis, Nekemias, Parthenocissus, Rhoicissus, and Vitis, with genus Vitis showing the lowest values up to a minimum of ~ 4.65 × 10−11 s/s/y. We suggest that liana-like species of Vitaceae evolve slower than erect growth habit plants and we invoke the "rate of mitosis hypothesis" to explain the observed pattern of the substitution rates. We identify a reduced set of 20 non-coding regions able to accurately reconstruct the phylogeny of Vitaceae and we provide a detailed description of all 152 non-coding regions identified in the plastomes of subg. Vitis. These polymorphic regions will find their applications in phylogenetics, phylogeography, and population genetics as well in grapes identification through DNA barcoding techniques. [ABSTRACT FROM AUTHOR]

The evolutionary lability of sex-determining mechanisms across the tree of life is well recognized, yet the extent of molecular changes that accompany these repeated transitions remain obscure. Most turtles retain the ancestral temperature-dependent sex determination (TSD) from which multiple transitions to genotypic sex determination (GSD) occurred independently, and two contrasting hypotheses posit the existence or absence of reversals back to TSD. Here we examined the molecular evolution of the coding regions of a set of gene regulators involved in gonadal development in turtles and several other vertebrates. We found slower molecular evolution in turtles and crocodilians compared to other vertebrates, but an acceleration in Trionychia turtles and at some phylogenetic branches demarcating major taxonomic diversification events. Of all gene classes examined, hormone signaling genes, and Srd5a1 in particular, evolve faster in many lineages and especially in turtles. Our data show that sex-linked genes do not follow a ubiquitous nor uniform pattern of molecular evolution. We then evaluated turtle nucleotide and protein evolution under two evolutionary hypotheses with or without GSD-to-TSD reversals, and found that when GSD-to-TSD reversals are considered, all transitional branches irrespective of direction, exhibit accelerated molecular evolution of nucleotide sequences, while GSD-to-TSD transitional branches also show acceleration in protein evolution. Significant changes in predicted secondary structure that may affect protein function were identified in three genes that exhibited hastened evolution in turtles compared to other vertebrates or in transitional versus non-transitional branches within turtles, rendering them candidates for a key role during SDM evolution in turtles. [ABSTRACT FROM AUTHOR]

Evolutionary constraint for insertions and deletions (indels) is not necessarily equal to constraint for nucleotide substitutions for any given region of a genome. Knowing the variation in indel-specific evolutionary rates across the sequence will aid our understanding of evolutionary constraints on indels, and help us infer how indels have contributed to the evolution of the sequence. However, unlike for nucleotide substitutions, there has been no phylogenetic method that can statistically infer significantly different rates of indels across the sequence space independent of substitution rates. Here, we have developed a software that will find sites with accelerated evolutionary rates specific to indels, by introducing a scaling parameter that only applies to the indel rates and not to the nucleotide substitution rates. Using the software, we show that we can find regions of accelerated rates of indels in the protein alignments of primate genomes. We also confirm that the sites that have high rates of indels are different from the sites that have high rates of nucleotide substitutions within the protein sequences. By identifying regions with accelerated rates of indels independent of nucleotide substitutions, we will be able to better understand the impact of indel mutations on protein sequence evolution. [ABSTRACT FROM AUTHOR]

Coral species are difficult to discern because of their morphological plasticity, long generation times, and slow rates of mitochondrial DNA evolution. Among Caribbean representatives of the genus Porites are three named species ( P. divaricata, P. furcata, and P. porites) with branching colony morphologies whose validity as genetically isolated species has been debated. We present sequence data from the mitochondrial control region, nuclear ITS, and nine single-copy nuclear loci for the Caribbean Porites and a related eastern Pacific species. mtDNA sequences were nearly invariant among the three branching species and their crustose sister P. branneri, and ITS sequences from these four were intermingled. An information theoretic analysis provided no support for upholding the three named Caribbean branching species. Both a clustering analysis and an analysis of molecular variance showed that sequence variation from the three branching forms is partitioned more by geography than by taxonomy. Multi-locus coalescent phylogenetic analysis provided a calibrated estimate for the nuclear DNA substitution rate (0.14 % Ma) close to that for other corals. Because no generalities have emerged from genetic investigations of the validity of morphologically defined coral species, the use of single-copy nuclear data is likely to be important in testing problematic species designations. [ABSTRACT FROM AUTHOR]

As recycling effluent from municipal sewage plants is technically a feasible way, this paper presents a mathematical model to analyze the extent to which effluent should be reclaimed for industrial use and examine the factor affecting reuse of reclaimed water. The resulting data shows that the low price of fresh water leads to reduced use of reclaimed water and impedes the investment of the effluent purification plant. A mandated regulation on the substitution rate of reclaimed water is suggested to impose on the industry. Theoretically, the optimal substitution rate as well as the water quality is determined by maximizing the total social welfare that results from the construction of conveyance channels and effluent purification plants. A case example is employed to derive the optimal substitution rate and water quality of reclaimed water. Through the numerical analysis, an effluent plant for treating 20,000 kl/day effluent with the substitution rate of 21.24 % is selected as the optimal solution. [ABSTRACT FROM AUTHOR]

Political indicators are widely used in academic writing and decision making, but remain controversial. This paper discusses the problems related to the aggregation functions they use. Almost always, political indicators are aggregated by weighted averages or summations. The use of such functions is based on untenable assumptions (existence of homogeneous substitution rates, total compensation, and strict monotonicity). We show through concrete examples how these hidden assumptions are likely to produce results that are basically an artifact of ad hoc decisions, which additionally contradict very fundamental notions common to all credible political theories. We suggest, also through example, that some-necessarily partial-solutions are possible. [ABSTRACT FROM AUTHOR]

As a means of heated debate, mass vaccination of poultry has been used in some countries to control H5N1 highly pathogenic avian influenza (HPAI), which remains of global economic and public health significance. Theoretically, mass vaccination can act as an evolutionary selective force facilitating the emergence of vaccine-resistant viruses, similar to that widespread use of antibiotics facilitates the emergence of antibiotic-resistant bacteria. To support the hypothesis, the substitution rates in the two subunits, HA1 and HA2, of the viral hemagglutinin gene, were calculated using a Bayesian Markov Chain Monte Carlo (MCMC) approach. It was found that the rate in the HA1 subunit, but not in the HA2 subunit, increased significantly during periods of mass vaccination (2005-2010 in China and 2003-2009 in Indonesia), in contrast to the periods when no mass vaccination programs took place (1996-2004 in China and 2004-2008 in Thailand). Because substitutions in the HA1 subunit rather than in the HA2 subunit can lead to vaccine-resistant viruses, the results support that mass vaccination programs facilitate the emergence of vaccine-resistant viruses, which, in turn, will render mass vaccination programs less effective. Therefore, caution must be taken when adopting mass vaccination as a long-term strategy to control HPAI. [ABSTRACT FROM AUTHOR]

Slower genetic evolution in microbial thermophiles has been attributed to internal mutation control mechanisms in very high temperatures, whereas the tempo of plant microevolution has been positively correlated to ambient thermal conditions. Here, using a global dataset of 136 teleost fish species, contrasting warm and cool water species, and controlling for any differences between species in mutation control mechanisms, we found mitochondrial genetic evolution was 1.61 times faster in warm water species. These results suggest that temperature-mediated reduction in mutation rate is only important in extreme thermal regimes. [ABSTRACT FROM AUTHOR]

Long Terminal Repeat retrotransposons (LTR-RTs) are a major component of several plant genomes. Important insights into the evolutionary dynamics of these elements in a genome are provided by the comparative study of their insertion times. These can be inferred by the comparison of pairs of LTRs flanking intact LTR-RTs in combination with an estimated substitution rate. Over the past several years, different substitution rates have been proposed for LTRs in crop plants. However, very little is known about the extent of substitution rate variation and the factors contributing to this variation, so the rates currently used are generally considered rough estimators of actual rates. To evaluate the extent of substitution rate variation in LTRs, we identified 70 orthologous LTRs on the short arms of chromosome 3 of both Oryza sativa and Oryza glaberrima, species that diverged ∼0.64 Ma. Since these orthologous sequences were present in a common ancestor prior to species divergence, nucleotide differences identified in comparing these regions must correspond to mutations accumulated post-speciation, thereby giving us the opportunity to study LTR substitution rate variation in different elements across these short arms. As a control, we analyzed a similar amount of non-repeat-related sequences collected near the orthologous LTRs. Our analysis showed that substitution rate variation in LTRs is greater than 5-fold, is positively correlated with G+C content, and tends to increase near centromeric regions. We confirmed that in the vast majority of cases, LTRs mutate faster than their corresponding non-repeat-related neighboring sequences. [ABSTRACT FROM AUTHOR]

Since plant mitochondrial genomes exhibit some of the slowest known synonymous substitution rates, it is generally believed that they experience exceptionally low mutation rates. However, the use of synonymous substitution rates to infer mutation rates depends on the implicit assumption that synonymous sites are evolving neutrally (or nearly so). To assess the validity of this assumption in plant mitochondrial genomes, we examined coding sequence for footprints of selection acting at synonymous sites. We found that synonymous sites exhibit an AT rich and pyrimidine skewed nucleotide composition compared to both non-synonymous sites and non-coding regions. We also found some evidence for selection associated with both biased codon usage and conservation of regulatory sequences involved in mRNA processing, although some of these findings are subject to alternative non-adaptive interpretations. Regardless, the inferred strength of selection appears too weak to account for the variation in substitution rates between the mitochondrial genomes of plants and other multicellular eukaryotes. Therefore, these results are consistent with the interpretation that plant mitochondrial genomes experience a substantially lower mutation rate rather than increased functional constraints acting on synonymous sites. Nevertheless, there are important nucleotide composition patterns (particularly the differences between synonymous sites and non-coding DNA) that remain largely unexplained. [ABSTRACT FROM AUTHOR]

The rapidly evolving mitochondrial control region remains an important source of information on phylogeography and demographic history for cetaceans and other vertebrates, despite great uncertainty in the rate of nucleotide substitution across both nucleotide positions and lineages. Patterns of variation in linked markers with slower rates of evolution can potentially be used to calibrate the rate of nucleotide substitution in the control region and to better understand the interplay of evolutionary and demographic forces across the mitochondrial genome above and below the species level. We have examined patterns of diversity within and between three baleen whale species (gray, humpback, and Antarctic minke whales) in order to determine how patterns of molecular evolution differ between cytochrome b and the control region. Our results show that cytochrome b is less variable than expected given the diversity in the control region for gray and humpback whales, even after functional differences are taken into account, but more variable than expected for minke whales. Differences in the frequency distributions of polymorphic sites and in best-fit models of nucleotide substitution indicate that these patterns may be the result of hypervariability in the control region in gray and humpback whales but, in minke whales, may result from a large, stable or expanding population size coupled with saturation at the control region. Using paired cytochrome b and control region data across individuals, we show that the average rate of nucleotide substitution in the control region may be on average 2.6 times higher than phylogenetically derived estimates in cetaceans. These results highlight the complexity of making inferences from control region data alone and suggest that applying simple rules of DNA sequence analyses across species may be difficult. [ABSTRACT FROM AUTHOR]

GB virus C/hepatitis G (GBV-C) is an RNA virus of the family Flaviviridae. Despite replicating with an RNA-dependent RNA polymerase, some previous estimates of rates of evolutionary change in GBV-C suggest that it fixes mutations at the anomalously low rate of ∼10−7 nucleotide substitution per site, per year. However, these estimates were largely based on the assumption that GBV-C and its close relative GBV-A (New World monkey GB viruses) codiverged with their primate hosts over millions of years. Herein, we estimated the substitution rate of GBV-C using the largest set of dated GBV-C isolates compiled to date and a Bayesian coalescent approach that utilizes the year of sampling and so is independent of the assumption of codivergence. This revealed a rate of evolutionary change approximately four orders of magnitude higher than that estimated previously, in the range of 10−2 to 10−3 sub/site/year, and hence in line with those previously determined for RNA viruses in general and the Flaviviridae in particular. In addition, we tested the assumption of host-virus codivergence in GBV-A by performing a reconciliation analysis of host and virus phylogenies. Strikingly, we found no statistical evidence for host-virus codivergence in GBV-A, indicating that substitution rates in the GB viruses should not be estimated from host divergence times. [ABSTRACT FROM AUTHOR]

The APOA5 gene, located in the APOA1/C3/A4/A5 gene cluster, is a key regulator of triglyceride metabolism. ApoAV plasma concentration is much lower as compared to other apolipoproteins such as apoCIII and apoAI. This is due in part to the fact that the APOC3-enhancer, which up-regulates transcription of the APOA1, APOC3, and APOA4 genes, does not increase expression of the APOA5 gene. We postulated that intervening Alu repeats in the APOA5-APOA4 intergenic region gene might be blocking action of the APOC3-enhancer over the APOA5-promoter. To search for evidence of functional significance of the intervening Alu sequences, we estimated nucleotide substitution rates of 21 pairs of Alu elements in the APOA5-APOA4 intergenic region by comparing published sequences of human and chimpanzee. Also, we scanned the intergenic region for the presence of binding sites of the insulator protein CTCF. Seven out of the nine found CTCF binding sites were located in the first half of the intergenic region. Five out of those seven CTCF binding sites were placed inside Alu elements. Based on their substitution rates, we found two clearly defined groups of Alu sequences: a slow-evolving group (mean 0.98 ± 0.18) and a fast-evolving group (mean 2.74 ± 0.54). Alu repeats with lower substitution rate tended to be located up to 14-kb upstream of the APOA5 gene, to belong to the oldest J-family and to have an opposite orientation to the APOA5 gene. Some Alu sequences may have functional relevance on the regulation of the APOA5-gene expression. [ABSTRACT FROM AUTHOR]

Interspecies divergence of orthologous transposable element remnants is often assumed to be simply due to genetic drift of neutral mutations that occurred after the divergence of the species. However, divergence may also be affected by other factors, such as variation in the mutation rate, ancestral polymorphisms, or selection. Here we attempt to determine the impact of these forces on divergence of three classes of sites that are often assumed to be selectively unconstrained (INE-1 TE remnants, sites within short introns, and fourfold degenerate sites) in two different pairwise comparisons of Drosophila ( D. melanogaster vs. D. simulans and D. simulans vs. D. sechellia). We find that divergence of these three classes of sites is strongly influenced by the recombination environment in which they are located, and this is especially true for the closer D. simulans vs. D. sechellia comparison. We suggest that this is mainly a result of the contribution of ancestral polymorphisms in different recombination regions. We also find that intergenic INE-1 elements are significantly more diverged than intronic INE-1 in both pairwise comparisons, implying the presence of either negative selection or lower mutation rates in introns. Furthermore, we show that substitution rates in INE-1 elements are not associated with the length of the noncoding sequence in which they are located, suggesting that reduced divergence in long noncoding sequences is not due to reduced mutation rates in these regions. Finally, we show that GC content for each site within INE-1 sequences has evolved toward an equilibrium value (∼33%) since insertion. [ABSTRACT FROM AUTHOR]

We assess the similarity of base substitution processes, described by empirically derived 4 × 4 matrices, using chi-square homogeneity tests. Such significance analyses allow us to assess variation in sequence evolution across sites and we apply them to matrices derived from noncoding sites in different contexts in grass chloroplast DNA. We show that there is statistically significant variation in rates and patterns of mutation among noncoding sites in different contexts and then demonstrate a similar and significant influence of context on substitutions at fourfold degenerate sites of coding regions from grass chloroplast DNA. These results show that context has the same general effect on substitution bias in coding and noncoding DNA: the A+T content of flanking bases is correlated with rate of substitution, transition bias, and GC → AT pressure, while the number of flanking pyrimidines on a single strand is correlated with a mutational bias, or skew, toward pyrimidines. Despite the similarity in general trends, however, when we compare coding and noncoding matrices we find that there is a statistically significant difference between them even when we control for context. Most noticeably, fourfold degenerate sites in coding sequences are undergoing substitution at a higher rate and there are also significant differences in the relationship between pyrimidines skew and the number of flanking pyrimidines. Possible reasons for the differences between coding and noncoding sites are discussed. Furthermore, our analysis illustrates a simple statistical way for comparing substitution processes across sites allowing us to better study variation in evolutionary processes across a genome. [ABSTRACT FROM AUTHOR]

In free-living microorganisms, such as Escherichia coli and Saccharomyces cerevisiae, both synonymous and nonsynonymous substitution frequencies correlate with expression levels. Here, we have tested the hypothesis that the correlation between amino acid substitution rates and expression is a by-product of selection for codon bias and translational efficiency in highly expressed genes. To this end, we have examined the correlation between protein evolutionary rates and expression in the human gastric pathogen Helicobacter pylori, where the absence of selection on synonymous sites enables the two types of substitutions to be uncoupled. The results revealed a statistically significant negative correlation between expression levels and nonsynonymous substitutions in both H. pylori and E. coli. We also found that neighboring genes located on the same, but not on opposite strands, evolve at significantly more similar rates than random gene pairs, as expected by co-expression of genes located in the same operon. However, the two species differ in that synonymous substitutions show a strand-specific pattern in E. coli, whereas the weak similarity in synonymous substitutions for neighbors in H. pylori is independent of gene orientation. These results suggest a direct influence of expression levels on nonsynonymous substitution frequencies independent of codon bias and selective constraints on synonymous sites. [ABSTRACT FROM AUTHOR]

Nonrandom patterns associated with adaptively evolving genes can shed light on how selection and mutation produce rapid changes in sequences. I examine such patterns in two independent families of antimicrobial peptide genes: those in frogs, which are known to have evolved under positive selection, and those in flatfishes, which I show have also evolved under positive selection. I address two recently proposed hypotheses about the molecular evolution of antimicrobial peptide genes. The first is that the mature peptide region is replicated by an error-prone polymerase that increases the mutation rate and the transversion/transition ratio compared to the signal sequence of the same genes. The second is that mature peptides evolve in a coordinated fashion with their propieces, such that a change in net charge in one molecular region prompts an opposite change in charge in the other region. I test these hypotheses using alternative methods that minimize alignment errors, correct for phylogenetic nonindependence, reduce sequence saturation, and account for differing selection pressures on different regions of the gene. In both gene families I show that divergence at both synonymous and nonsynonymous sites within the mature peptide region is enhanced. However, in neither gene family is there evidence of an increased mutational transversion/transition ratio or coordinated evolution. My observations are consistent with either an elevated mutation rate in an adaptively evolving gene region or widespread selection on “silent” sites. These hypotheses challenge the assumption that mutations are random and can be measured by the synonymous substitution rate. [ABSTRACT FROM AUTHOR]

As a protein-encoding gene evolves, different selective pressures act on the gene temporally and spatially. An examination of the ratio of nonsynonymous-to-synonymous nucleotide substitution rate ratios ( Ka/ Ks) has proven to be a valuable method to examine selective pressures on protein encoding genes, including detecting positive diversifying selection. To gain power over averaging all sites in a gene together, examination of sites in primary sequence windows has frequently been employed. However, selection acts on folded proteins and sites that are close in tertiary space may not be close in primary sequence. A new method for the examination of Ka/ Ks ratios based upon windows in tertiary structure is introduced and applied to the leptin gene family in mammals. Tertiary sequence windowing detects new sites under positive diversifying selection and detects positive diversifying selection with a more significant signal along various branches of the leptin gene family tree. [ABSTRACT FROM AUTHOR]

Recent work has shown thatDrosophila melanogastergenes with fast-evolving nonsynonymous sites have lower codon usage bias. This pattern has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. Here we have looked for this correlation in a much larger and less biased dataset, comprising 630 gene pairs fromD. melanogasterandD. yakuba. We confirmed that there is a negative correlation between the rate of nonsynonymous substitutions (dN) and codon bias inD. melanogaster. We then tested the interference hypothesis and other alternative explanations, including one involving gene expression. We found thatdN indeed correlates with the level of gene expression. Given that gene expression is a strong determinant of codon bias, the relationship betweendN and codon bias might be a by-product of gene expression. However, our tests show that none of the hypotheses we consider seem to explain the data fully. [ABSTRACT FROM AUTHOR]

Accurate estimation of relative mutation rates of mitochondrial DNA (mtDNA) and single-copy nuclear DNA (scnDNA) within lineages contributes to a general understanding of molecular evolutionary processes and facilitates making demographic inferences from population genetic data. The rate of divergence at synonymous sites (Ks) may be used as a surrogate for mutation rate. Such data are available for few organisms and no amphibians. Relative to mammals and birds, amphibian mtDNA is thought to evolve slowly, and the Ks ratio of mtDNA to scnDNA would be expected to be low as well. Relative Ks was estimated from a mitochondrial gene, ND2, and a nuclear gene, c-myc, using both “approximate” and likelihood methods. Three lineages of congeneric frogs were studied and this ratio was found to be approximately 16, the highest of previously reported ratios. No evidence of a low Ks in the nuclear gene was found: c-myc codon usage was not biased, the Ks was double the intron divergence rate, and the absolute Ks was similar to estimates obtained here for other genes from other frog species. A high Ks in mitochondrial vs. nuclear genes was unexpected in light of previous reports of a slow rate of mtDNA evolution in amphibians. These results highlight the need for further investigation of the effects of life history on mutation rates. [ABSTRACT FROM AUTHOR]

Molecular data are ideal for exploring evolutionary history because of its universality, stochasticity, and abundance. These features provide a means of exploring the evolutionary history of all organisms (including those that do not tend to leave fossils), potentially within a statistical framework that allows testing of evolutionary hypotheses. However, the discrepancy between molecular and paleontological dates for three key “explosive” radiations inferred from the fossil record—the Cambrian explosion of animal phyla and the post-KT radiations of modern orders of mammals and birds—have led to a reexamination of the assumptions on which molecular dates are based. Could variation in the rate of molecular evolution, perhaps associated with “explosive” radiations, cause overestimation of diversification dates? Here I examine four hypothetical causes of fast molecular rates in explosive radiations—body size, morphological rate, speciation rate, and ecological diversification—using available empirical evidence on patterns of variation in rate of molecular evolution. [ABSTRACT FROM AUTHOR]

We examined rates of DNA sequence evolution in 12 populations of Escherichia coli propagated in a glucose minimal medium for 20,000 generations. Previous work saw mutations mediated by mobile elements in these populations, but the extent of other genomic changes was not investigated. Four of the populations evolved defects in DNA repair and became mutators. Some 500 bp was sequenced in each of 36 genes for 50 clones, including 2 ancestral variants, 2 clones from each population at generation 10,000, and 2 from each at generation 20,000. Ten mutations were found in total, all point mutations including mostly synonymous substitutions and nonsynonymous polymorphisms; all 10 were found in mutator populations. We compared the observed sequence evolution to predictions based on different scenarios. The number of synonymous substitutions is lower than predicted from measured mutation rates in E. coli, but the number is higher than rates based on comparing E. coli and Salmonella genomes. Extrapolating to the entire genome, these data predict about 250 synonymous substitutions on average per mutator population, but only about 3 synonymous substitutions per nonmutator population, during 20,000 generations. These data illustrate the challenge of finding sequence variation among bacterial isolates that share such a recent ancestor. However, this limited variation also provides a useful baseline for research aimed at finding the beneficial substitutions in these populations. [ABSTRACT FROM AUTHOR]

The study of rates of nucleotide substitution in RNA viruses is central to our understanding of their evolution. Herein we report a comprehensive analysis of substitution rates in 50 RNA viruses using a recently developed maximum likelihood phylogenetic method. This analysis revealed a significant relationship between genetic divergence and isolation time for an extensive array of RNA viruses, although more rate variation was usually present among lineages than would be expected under the constraints of a molecular clock. Despite the lack of a molecular clock, the range of statistically significant variation in overall substitution rates was surprisingly narrow for those viruses where a significant relationship between genetic divergence and time was found, as was the case when synonymous sites were considered alone, where the molecular clock was rejected less frequently. An analysis of the ecological and genetic factors that might explain this rate variation revealed some evidence of significantly lower substitution rates in vector-borne viruses, as well as a weak correlation between rate and genome length. Finally, a simulation study revealed that our maximum likelihood estimates of substitution rates are valid, even if the molecular clock is rejected, provided that sufficiently large data sets are analyzed. [ABSTRACT FROM AUTHOR]

The relationship between the silent substitution rate (Ks) and the GC content along the genome is a focal point of the debate about the origin of the isochore structure in vertebrates. Recent estimation of the silent substitution rate showed a positive correlation between Ks and GC content, in contradiction with the predictions of both the regional mutation bias model and the selection or biased gene conversion model. The aim of this paper is to help resolve this contradiction between theoretical studies and data. We analyzed the relationship between Ks and GC content under (1) uniform mutation bias, (2) a regional mutation bias, and (3) mutation bias and selection. We report that an increase in Ks with GC content is expected under mutation bias because of either nonequilibrium of the isochore structure or an increasing mutation rate from AT toward GC nucleotides in GC-richer isochores. We show by simulations that CpG deamination tends to increase the mutation rate with GC content in a regional mutation bias model. We also demonstrate that the relationship between Ks and GC under the selectionist or biased gene conversion model is positive under weak selection if the mutation selection equilibrium GC frequency is less than 0.5. [ABSTRACT FROM AUTHOR]

Twelve MHC class I exon 2 sequences were uncovered in a sample from the endangered Sacramento River winter-run Chinook salmon in the central valley of California. Phylogenetic analysis of the 12 sequences indicates that the alleles descend from two of six major allelic lineages found among four Pacific salmon species. Nine of the 12 alleles belong to an allelic lineage that began diversifying 8 million years ago, just prior to the estimated time of Chinook speciation. The most recent common ancestor of all 12 winter-run alleles is estimated to be 15 million years ago, approximately 5 million years before the radiation of the Pacific salmon species. The average nonsynonymous distance among the peptide binding-region codons of exon 2 for the 12 alleles is significantly higher than the average synonymous distance in these codons. We estimate the symmetrical overdominant selection coefficient against homozygotes for this exon to be 0.038. Thus, strong positive and balancing selection has maintained functional diversity in the peptide-binding region of the exon over millions of years and this variation has not yet been substantially eliminated by increased genetic drift due to the recent dramatic decline in abundance of this Chinook salmon population. [ABSTRACT FROM AUTHOR]

Bighorn sheep populations have greatly declined in numbers and distribution since European settlement, primarily because of high susceptibility to infectious diseases transmitted to them from domestic livestock. It has been suggested that low variation at major histocompatibility complex (MHC) genes, the most important genetic aspect of the vertebrate immune system, may result in high susceptibility to infectious disease. Therefore, we examined genetic polymorphism at a MHC gene (Ovca-DRB) in a large sample, both numerically and geographically, of bighorn sheep. Strikingly, there were 21 different alleles that showed extensive nucleotide and amino acid sequence divergence. In other words, low MHC variation does not appear to be the basis of the high disease susceptibility and decline in bighorn sheep. On the other hand, analysis of the pattern of the MHC polymorphism suggested that nonsynonymous substitutions predominated, especially at amino acids in the antigen-binding site. The average overall heterozygosity for the 16 amino acid positions that are part of the antigen binding site is 0.389 whereas that for the 67 amino acid positions not involved with antigen binding is 0.076. These findings imply that the diversity present in this gene is functionally significant and is, or has been, maintained by balancing selection. To examine the evolution of DRB alleles in related species, a phylogenetic analysis including other published ruminant (Bovidae and Cervidae) species, was carried out. An intermixture of sequences from bighorn sheep, domestic sheep, goats, cattle, bison, and musk ox was observed supporting trans-species polymorphism for these species. To reconcile the species and gene trees for the 104 sequences examined, 95 ‘deep coalescent’ events were necessary, illustrating the importance of balancing selection maintaining variation over speciation events. [ABSTRACT FROM AUTHOR]

Whether the mutation rate differs between sexes has been a matter of discussion for years. Molecular analyses of mammals have indicated that males mutate more often than females, as manifested by the faster rate of neutral sequence evolution on the Y chromosome than on the X chromosome. However, these observations can as well be interpreted as specific reduction of the X chromosome mutation rate, which would be adaptive because of reducing the number of slightly deleterious recessive mutations exposed in hemizygote males. Recently, data from birds have suggested that vertebrate mutation rates may indeed be male-biased. In birds, females are the heterogametic sex (ZW), and analyses of the Z-linked CHD1Z gene have shown that it evolves faster than its W-linked and thus female-specific homologue, CHD1W. We have now studied the second avian gene known to exist in a copy on the nonrecombining regions of both the Z and the W chromosome, viz., the ATP synthase α-subunit (ATP5A1). In independent comparisons of three pairs of bird species from divergent lineages, intron sequences of the Z-linked copy (ATP5A1Z) were consistently found to evolve faster than the W-linked copy (ATP5A1W). From these data we calculated male-to-female mutation rate ratios (α) of 1.8, 2.3, and 5.0 in Galliform, Anseriform, and Ciconiiform lineages, respectively. Therefore, this study provides independent support for a male-biased mutation rate in birds. [ABSTRACT FROM AUTHOR]

One of the most useful features of molecular phylogenetic analyses is the potential for estimating dates of divergence of evolutionary lineages from the DNA of extant species. But lineage-specific variation in rate of molecular evolution complicates molecular dating, because a calibration rate estimated from one lineage may not be an accurate representation of the rate in other lineages. Many molecular dating studies use a ``clock test'' to identify and exclude sequences that vary in rate between lineages. However, these clock tests should not be relied upon without a critical examination of their effectiveness at removing rate variable sequences from any given data set, particularly with regard to the sequence length and number of variable sites. As an illustration of this problem we present a power test of a frequently employed triplet relative rates test. We conclude that (1) relative rates tests are unlikely to detect moderate levels of lineage-specific rate variation (where one lineage has a rate of molecular evolution 1.5 to 4.0 times the other) for most commonly used sequences in molecular dating analyses, and (2) this lack of power is likely to result in substantial error in the estimation of dates of divergence. As an example, we show that the well-studied rate difference between murid rodents and great apes will not be detected for many of the sequences used to date the divergence between these two lineages and that this failure to detect rate variation is likely to result in consistent overestimation the date of the rodent–primate split. [ABSTRACT FROM AUTHOR]

To understand the process and mechanism of protein evolution, it is important to know what types of amino acid substitutions are more likely to be under selection and what types are mostly neutral. An amino acid substitution can be classified as either conservative or radical, depending on whether it involves a change in a certain physicochemical property of the amino acid. Assuming Kimura's two-parameter model of nucleotide substitution, I present a method for computing the numbers of conservative and radical nonsynonymous (amino acid altering) nucleotide substitutions per site and estimate these rates for 47 nuclear genes from mammals. The results are as follows. (1) The average radical/conservative rate ratio is 0.81 for charge changes, 0.85 for polarity changes, and 0.49 when both polarity and volume changes are considered. (2) The radical/conservative rate ratio is positively correlated with the nonsynonymous/synonymous rate ratio for charge changes or when both polarity and volume changes are considered. (3) Both the conservative/synonymous rate ratio and the radical/synonymous rate ratio are lower in the rodent lineage than in the primate or artiodactyl lineage, suggesting more intense purifying selection in the rodent lineage, for both conservative and radical nonsynonymous substitutions. (4) Neglecting transition/transversion bias would cause an underestimation of both radical and conservative rates and the ratio thereof. (5) Transversions induce more dramatic genetic alternations than transitions in that transversions produce more amino acid altering changes and among which, more radical changes. [ABSTRACT FROM AUTHOR]

In sexual populations, beneficial mutations that occur in different lineages may be recombined into a single lineage. In asexual populations, however, clones that carry such alternative beneficial mutations compete with one another and, thereby, interfere with the expected progression of a given mutation to fixation. From theoretical exploration of such ‘clonal interference’, we have derived (1) a fixation probability for beneficial mutations, (2) an expected substitution rate, (3) an expected coefficient of selection for realized substitutions, (4) an expected rate of fitness increase, (5) the probability that a beneficial mutation transiently achieves polymorphic frequency (≥ 1%), and (6) the probability that a beneficial mutation transiently achieves majority status. Based on (2) and (3), we were able to estimate the beneficial mutation rate and the distribution of mutational effects from changes in mean fitness in an evolving E. coli population. [ABSTRACT FROM AUTHOR]

The detailed descriptions now available for the secondary structure of small-ribosomalsubunit RNA, including areas of higly variable primary structure, facilitate the alignment of nucleotide sequences. However, for optimal exploitation of the information contained in the alignment, a method must be available that takes into account the local sequence variability in the computation of evolutionary distance. A quantitative definition for the variability of an alignment position is proposed in this study. It is a parameter in an equation which expresses the probability that the alignment position contains a different nucleotide in two sequences, as a function of the distance separating these sequences, i.e., the number of substitutions per nucleotide that occurred during their divergence. This parameter can be estimated from the distance matrix resulting from the conversion of pairwise sequence dissimilarities into pairwise distances. Alignment positions can then be subdivided into a number of sets of matching variability, and the average variability of each set can be derived. Next, the conversion of dissimilarity into distance can be recalculated for each set of alignment positions separately, using a modified version of the equation that corrects for multiple substitutions and changing for each set the parameter that reflects its average variability. The distances computed for each set are finally averaged, giving a more precise distance estimation. Trees constructed by the algorithm based on variability calibration have a topology markedly different from that of trees constructed from the same alignments in the absence of calibration. This is illustrated by means of trees constructed from small-ribosomal-subunit RNA sequences of Metazoa. A reconstruction of vertebrate evolution based on calibrated alignments matches the consensus view of paleontologists, contrary to trees based on uncalibrated alignments. In trees derived from sequences covering several metazoan phyla, artefacts in topology that are probably due to a high clock rate in certain lineages are avoided. [ABSTRACT FROM AUTHOR]

We introduce a general class of models for sequence evolution that includes network phylogenies. Networks, a generalization of strictly tree-like phylogenies, are proposed to model situations where multiple lineages contribute to the observed sequences. An algorithm to compute the probability distribution of binary character-state configurations is presented and statistical inference for this model is developed in a likelihood framework. A stepwise procedure based on likelihood ratios is used to explore the space of models. Starting with a star phylogeny, new splits (nontrivial bipartitions of the sequence set) are successively added to the model until no significant change in the likelihood is observed. A novel feature of our approach is that the new splits are not necessarily constrained to be consistent with a treelike mode of evolution. The fraction of invariable sites is estimated by maximum likelihood simultaneously with other model parameters and is essential to obtain a good fit to the data. The effect of finite sequence length on the inference methods is discussed. Finally, we provide an illustrative example using aligned VPl genes from the foot and mouth disease viruses (FMDV). The different serotypes of the FMDV exhibit a range of treelike and network evolutionary relationships. [ABSTRACT FROM AUTHOR]

Two P-elements (bif1 and bif2) were isolated from a genomic library of Drosophila bifasciata. Both elements are internally deleted and have lost the coding capacity for a functional transposase. One of the elements (bif2) contains an insert consisting of a repetitive sequence. The terminal inverted repeats and the segments necessary for passive mobility are well conserved. Element bif2 has retained rudiments of the coding sequence of exon 0 and exon 3, but the reading frame is destroyed by insertions and deletions. The comparison of the D. bifasciata P-elements with P-elements of Drosophila melanogaster and Drosophila nebulosa reveals that the two latter sequences are more similar to each other than either of them is to the D. bifasciata elements. This finding contradicts the phylogenetic relationship of the species and can be taken as an indirect but unequivocal evidence for recent horizontal gene transfer from a relative of D. nebulosa to the gene pool of D. melanogaster. The P-elements of D. bifasciata are phylogenetically ancient and have evolved independently for about 50 million years. A higher substitution rate at the third codon position as well as a predominance of conservative replacements at the amino acid level indicates that the P-elements of D. bifasciata have been under selective constraint over a long period and that immobilization has occurred only recently. [ABSTRACT FROM AUTHOR]

One of the pupal cuticle protein (PCP) genes has been found within an intron of a Drosophila housekeeping gene (the Gart locus) that encodes three enzymes involved in the purine pathway. This intronic gene has been described as a gene within a gene, and the gene is now called a 'nested' gene. Because the intronic PCP gene has sequence similarity with the larval cuticle protein (LCP) gene, it may have been derived from one of the LCP genes or their ancestral gene. We have studied possible phylogenetic relationships among these five genes by comparing nucleotide sequences of four LCP genes with that of the PCP gene. The results obtained suggest that the PCP gene may have originated from an ancestral gene before duplication of the LCP genes occurred. Using the number of synonymous (silent) substitutions, we then estimated the divergence time between the PCP gene and the LCP genes to be about 70 million years (Myr). The divergence time estimated is much larger than that for the sibling species of D. melanogaster (about 2.5 Myr), indicating that the 'nested' gene structure can be seen not only in Drosophila melanogaster, but also in other distantly related Drosophila species. [ABSTRACT FROM AUTHOR]

Sea urchin and rodent genomes have been posited to evolve rapidly as indicated by divergences in single copy nuclear DNA sequences. We have examined whether the synonymous substitution rates of three highly conserved genes, β-tubulin, histone H4, and histone H3, adhere to these high genomic substitution rates by comparing sequences between two sea urchins, Strongylocentrotus purpuratus and Lytechinus pictus, and between rodents and humans. Whereas the rate of change between the 3′ untranslated regions of the β-tubulin cDNA of S. purpuratus (Sp-β1), sequenced in this study, and of L. pictus (Lp-β3) was consistent with the overall rate of change estimated from previous DNA hybridization results between these species, the synonymous substitution rates for the carboxyl domains of these β-tubulins, as well as for the late histones H4 and H3, were significantly depressed. In contrast, synonymous nucleotide substitution rates between rodents and between rodent and human for the carboxyl domain proper of identical β-tubulin isotypes and for histone H4 and H3.1 did not differ from the overall rate of change for the rodent genomes. Moreover, an analysis of paralogous human and mouse β-tubulin sequences supported the conclusion that the synonymous substitution rates in the mouse were higher than those in the human. Differences in constraint on evolutionary change were not evident strictly from the conserved amino acid sequences and base compositions of these genes. Other constraining influences seemed more relevant to the departure of the synonymous substitution rates of the sea urchin β-tubulin and histone coding regions from the average genomic rate. [ABSTRACT FROM AUTHOR]

We studied 10 protein-coding mitochondrial genes from 19 mammalian species to evaluate the effects of 10 amino acid properties on the evolution of the genetic code, the amino acid composition of proteins, and the pattern of nonsynonymous substitutions. The 10 amino acid properties studied are the chemical composition of the side chain, two polarity measures, hydropathy, isoelectric point, volume, aromaticity, aliphaticity, hydrogenation, and hydroxythiolation. The genetic code appears to have evolved toward minimizing polarity and hydropathy but not the other seven properties. This can be explained by our finding that the presumably primitive amino acids differed much only in polarity and hydropathy, but little in the other properties. Only the chemical composition (C) and isoelectric point (IE) appear to have affected the amino acid composition of the proteins studied, that is, these proteins tend to have more amino acids with typical C and IE values, so that nonsynonymous mutations tend to result in small differences in C and IE. All properties, except for hydroxythiolation, affect the rate of nonsynonymous substitution, with the observed amino acid changes having only small differences in these properties, relative to the spectrum of all possible nonsynonymous mutations. [ABSTRACT FROM AUTHOR]

Evolutionary divergence times can be inferred from molecular distances if a molecular clock can be assumed and if the substitution rate can be estimated. We present new evidence from relative rate tests that the rate of substitution at fourfold degenerate sites of nuclear genome-coding DNA is uniform in primate and rodent lineages. We also review recent relative rate test results showing substitution rate uniformity in the nuclear genome of simian primates. DNA distances between a range of mammalian taxa shows that a molecular clock is inconsistent with many assumed divergence times irrespective of the assumed substitution rate. We find that the substitution rate that implies the best compromise fit with divergence times across the range of taxa is 2.0–2.25 × 10-9. This range of substitution rates implies a divergence time of humans and chimpanzees of 4.0-3.6 million years ago. This postdates the occurrence of Ardipithecus ramidus and the earliest occurrence of Australopithecus 0afarensis, suggesting that the common ancestor of humans and chimpanzees was bipedal and that the trait has been lost in chimpanzees rather than gained in humans. [ABSTRACT FROM AUTHOR]

Substitution rates were estimated for the coding and noncoding regions of the hepatitis delta virus (HDV). The estimated rates of synonymous substitution in HDV were lower than the rates of substitution at nonsynonymous sites and in the noncoding region. HDV has lower synonymous substitution rates than the hepatitis C virus, though both are RNA viruses. The relatively low rate of synonymous substitution in HDV may be due to a strong preference of G and C nucleotides at third codon positions. Variation in substitution rate among HDV lineages may be correlated with the clinical development of the HDV-induced hepatitis. The phylogenetic tree inferred for 24 HDV strains reveals similarities between lineages isolated from the same geographic region. [ABSTRACT FROM AUTHOR]

Using sequence data from the last introns of ZFX and ZFY genes, we previously estimated the male-to-female ratio (α) of mutation rate to be close to 6 in higher primates and 1.8 in rodents. As the mutation rate may vary among different regions of the mammalian genome, it is interesting to see whether sequence data from other regions will give similar estimates. In this study, we have determined the partial genomic sequences of the ubiquitin-activating enzyme El genes ( Ube 1x and Ube 1y for the X-linked and Y-linked homologues, respectively) of mice and rats and two mouse Ube 1y pseudogenes. From the intron sequences of the Ube 1 genes, we calculated the divergence of the Y-linked genes ( Y = 0.161) and that of the X-linked genes ( X = 0.107) between mouse and rat, and found the Y/X ratio to be 1.50. This ratio led to an estimate of α = 2.0 with a 95% confidence interval of (1.0, 3.9). Similar estimates of α were obtained if mouse Ube 1y pseudogenes were used instead of the mouse Ube 1y functional gene. These estimates are consistent with our previous estimate for rodents and suggest that the sex ratio of mutation rate in rodents is approximately only one-third of that in higher primates. Our estimate of the divergence time between Ube 1x and Ube 1y supports the view that the two genes separated before the eutherian radiation. [ABSTRACT FROM AUTHOR]

Pho regulon is a highly evolved and conserved mechanism across the microbes to fulfil their phosphate need. In this study, 52 proteobacteria genomes were analyzed for the presence of phosphorus acquisition genes, their pattern of arrangement and copy numbers. The diverse genetic architecture of the Pho regulon genes indicates the evolutionary challenge of nutrient limitation, particularly phosphorus, faced by bacteria in their environment. The incongruence between the Pho regulon proteins phylogeny and species phylogeny along with the presence of additional copies of pstS and pstB genes, having cross similarity with other genera, suggest the possibility of horizontal gene transfer event. The substitution rate analysis and multiple sequence alignment of the Pho regulon proteins were analyzed to gain additional insight into the evolution of the Pho regulon system. This comprehensive study confirms that genes perform the regulatory function (phoBR) were vertically inherited, whereas interestingly, genes whose product involved in direct interaction with the environment (pstS) acquired by horizontal gene transfer. The substantial amino acid substitutions in PstS most likely contribute to the successful adaptation of bacteria in different ecological condition dealing with different phosphorus availability. The findings decipher the intelligence of the bacteria which enable them to carry out the targeted alteration of genes to cope up with the environmental condition. [ABSTRACT FROM AUTHOR]

This is the first study reporting whole genome sequences of two CHIKV strains (KJ679577 and KJ679578) isolated from Eastern Indian patients sera during 2010-2011 outbreak, both of which were of ECSA genotype, but from different subgroups: Indian Ocean outbreak and ECSA subtypes. Furthermore, viral sequences were analyzed using different in-silico approaches to identify potential genetic variations that might have functional implications on various aspects of virus replication, viral protein functionality, immunogenicity and transmission. Epitope prediction analysis revealed 70.9% increase in number of MHC Class-II interacting epitopes of KJ679578 and 25-28% increase in Class-I interacting epitopes of KJ679577 and KJ679578 compared to that of EF027141 (CHIKV of Asian genotype circulating in India during 1973, after which CHIKV infection disappeared from India for three decades). CHIKV peptides DLAKLAFKRSSKYDLECAQIPVHMKSDA and KVVLCGDPKQCGFFNMMQMKYNYNHNI were predicted to interact with maximum number of HLA Class-I (68 and 76.5%, respectively) and Class-II (47 and 100%, respectively) alleles present within Indian population with allele frequency of > 0.1 and were also recognized as predicted B-cell epitopes with BCPred score between 0.766 and 0.961 and with antigenicity ranging from 0.52 to 1.69; thus these peptides might be used to induce T- and B-cell-mediated immunity against CHIKV. Thus, the present study might help to bridge the gap between virus microevolution and its implication in host immunity by taking into account viral genetic and conformational changes. Predicted epitopes might be used as promising targets for peptide-based vaccine development and rapid diagnostics against CHIKV infection. [ABSTRACT FROM AUTHOR]