Identification of physicochemical selective pressure on protein encoding nucleotide sequences

BACKGROUND: Statistical methods for identifying positively selected sites in protein coding regions are one of the most commonly used tools in evolutionary bioinformatics. However, they have been limited by not taking the physiochemical properties of amino acids into account. RESULTS: We develop a new codon-based likelihood model for detecting site-specific selection pressures acting on specific physicochemical properties. Nonsynonymous substitutions are divided into substitutions that differ with respect to the physicochemical properties of interest, and those that do not. The substitution rates of these two types of changes, relative to the synonymous substitution rate, are then described by two parameters, γ and ω respectively. The new model allows us to perform likelihood ratio tests for positive selection acting on specific physicochemical properties of interest. The new method is first used to analyze simulated data and is shown to have good power and accuracy in detecting physicochemical selective pressure. We then re-analyze data from the class-I alleles of the human Major Histocompatibility Complex (MHC) and from the abalone sperm lysine. CONCLUSION: Our new method allows a more flexible framework to identify selection pressure on particular physicochemical properties

Genomic hotspots for adaptation: the population genetics of Müllerian mimicry in Heliconius erato

This is the final version of the article. Available from the publisher via the DOI in this record.Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic examples of Mendelian loci of large effect, where allelic variation causes large and discrete phenotypic changes and is responsible for both convergent and highly divergent wing pattern evolution across the genus. We characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD), and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato. Despite very strong natural selection on color pattern, we see neither a strong reduction in genetic diversity nor evidence for extended LD across either patterning interval. This observation highlights the extent that recombination can erase the signature of selection in natural populations and is consistent with the hypothesis that either the adaptive radiation or the alleles controlling it are quite old. However, across both patterning intervals we identified SNPs clustered in several coding regions that were strongly associated with color pattern phenotype. Interestingly, coding regions with associated SNPs were widely separated, suggesting that color pattern alleles may be composed of multiple functional sites, conforming to previous descriptions of these loci as "supergenes." Examination of gene expression levels of genes flanking these regions in both H. erato and its co-mimic, H. melpomene, implicate a gene with high sequence similarity to a kinesin as playing a key role in modulating pattern and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages. The complex genetic architecture at these color pattern loci stands in marked contrast to the single casual mutations often identified in genetic studies of adaptation, but may be more indicative of the type of genetic changes responsible for much of the adaptive variation found in natural populations.Funding: Funding for this study was provided by National Science Foundation grants to WOM (DEB-0715096 and IBN-0344705) and BAC (DEB-0513424). Funding for work on H. melpomene came from a BBSRC grant to CDJ and RHf-C (011845). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Baryon Washout, Electroweak Phase Transition, and Perturbation Theory

We analyze the conventional perturbative treatment of sphaleron-induced baryon number washout relevant for electroweak baryogenesis and show that it is not gauge-independent due to the failure of consistently implementing the Nielsen identities order-by-order in perturbation theory. We provide a gauge-independent criterion for baryon number preservation in place of the conventional (gauge-dependent) criterion needed for successful electroweak baryogenesis. We also review the arguments leading to the preservation criterion and analyze several sources of theoretical uncertainties in obtaining a numerical bound. In various beyond the standard model scenarios, a realistic perturbative treatment will likely require knowledge of the complete two-loop finite temperature effective potential and the one-loop sphaleron rate.Comment: 25 pages, 9 figures; v2 minor typos correcte

Deformation of Codimension-2 Surface and Horizon Thermodynamics

The deformation equation of a spacelike submanifold with an arbitrary codimension is given by a general construction without using local frames. In the case of codimension-1, this equation reduces to the evolution equation of the extrinsic curvature of a spacelike hypersurface. In the more interesting case of codimension-2, after selecting a local null frame, this deformation equation reduces to the well known (cross) focusing equations. We show how the thermodynamics of trapping horizons is related to these deformation equations in two different formalisms: with and without introducing quasilocal energy. In the formalism with the quasilocal energy, the Hawking mass in four dimension is generalized to higher dimension, and it is found that the deformation of this energy inside a marginal surface can be also decomposed into the contributions from matter fields and gravitational radiation as in the four dimension. In the formalism without the quasilocal energy, we generalize the definition of slowly evolving future outer trapping horizons proposed by Booth to past trapping horizons. The dynamics of the trapping horizons in FLRW universe is given as an example. Especially, the slowly evolving past trapping horizon in the FLRW universe has close relation to the scenario of slow-roll inflation. Up to the second order of the slowly evolving parameter in this generalization, the temperature (surface gravity) associated with the slowly evolving trapping horizon in the FLRW universe is essentially the same as the one defined by using the quasilocal energy.Comment: Latex, 61 pages, no figures; v2, type errors corrected; v3, references and comments are added, English is improved, to appear in JHE

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Comparison of diagnostic tests for the detection of Brucella spp. in camel sera

<p>Abstract</p> <p>Background</p> <p>Brucellosis in livestock causes enormous losses for economies of developing countries and poses a severe health risk to consumers of dairy products. Little information is known especially on camel brucellosis and its impact on human health. For surveillance and control of the disease, sensitive and reliable detection methods are needed. Although serological tests are the mainstay of diagnosis in camel brucellosis, these tests have been directly transposed from cattle without adequate validation. To date, little information on application of real-time PCR for detection of <it>Brucella </it>in camel serum is available. Therefore, this study was performed to compare the diagnostic efficiency of different serological tests and real-time PCR in order to identify the most sensitive, rapid and simple combination of tests for detecting <it>Brucella </it>infection in camels.</p> <p>Findings</p> <p>A total of 895 serum samples collected from apparently healthy Sudanese camels was investigated. Sudan is a well documented endemic region for brucellosis with cases in humans, ruminants, and camels. Rose Bengal Test (RBT), Complement Fixation Test (CFT), Slow Agglutination Test (SAT), Competitive Enzyme Linked Immunosorbant Assay (cELISA) and Fluorescence Polarization Assay (FPA) as well as real-time PCR were used. Our findings revealed that <it>bcsp31 </it>kDa real-time PCR detected <it>Brucella </it>DNA in 84.8% (759/895) of the examined samples, of which 15.5% (118/759) were serologically negative. Our results show no relevant difference in sensitivity between the different serological tests. FPA detected the highest number of positive cases (79.3%) followed by CFT (71.4%), RBT (70.7%), SAT (70.6%) and cELISA (68.8%). A combination of real-time PCR with one of the used serological tests identified brucellosis in more than 99% of the infected animals. 59.7% of the examined samples were positive in all serological tests and real-time PCR. A subpopulation of 6.8% of animals was positive in all serological tests but negative in real-time PCR assays. The high percentage of positive cases in this study does not necessarily reflect the seroprevalence of the disease in the country but might be caused by the fact that the camels were imported from brucellosis infected herds of Sudan, accidentally. Seroprevalence of brucellosis in camels should be examined in confirmatory studies to evaluate the importance of brucellosis in this animal species.</p> <p>Conclusion</p> <p>We suggest combining <it>bcsp31 </it>real-time PCR with either FPA, CFT, RBT or SAT to screen camels for brucellosis.</p

A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes

Protein-coding genes in eukaryotes are interrupted by introns, but intron densities widely differ between eukaryotic lineages. Vertebrates, some invertebrates and green plants have intron-rich genes, with 6–7 introns per kilobase of coding sequence, whereas most of the other eukaryotes have intron-poor genes. We reconstructed the history of intron gain and loss using a probabilistic Markov model (Markov Chain Monte Carlo, MCMC) on 245 orthologous genes from 99 genomes representing the three of the five supergroups of eukaryotes for which multiple genome sequences are available. Intron-rich ancestors are confidently reconstructed for each major group, with 53 to 74% of the human intron density inferred with 95% confidence for the Last Eukaryotic Common Ancestor (LECA). The results of the MCMC reconstruction are compared with the reconstructions obtained using Maximum Likelihood (ML) and Dollo parsimony methods. An excellent agreement between the MCMC and ML inferences is demonstrated whereas Dollo parsimony introduces a noticeable bias in the estimations, typically yielding lower ancestral intron densities than MCMC and ML. Evolution of eukaryotic genes was dominated by intron loss, with substantial gain only at the bases of several major branches including plants and animals. The highest intron density, 120 to 130% of the human value, is inferred for the last common ancestor of animals. The reconstruction shows that the entire line of descent from LECA to mammals was intron-rich, a state conducive to the evolution of alternative splicing

New taxa of Neosartorya and Aspergillus in Aspergillus section Fumigati

Three new species of Neosartorya and one new Aspergillus of section Fumigati are proposed using a polyphasic approach based on morphology, extrolite production and partial β-tubulin, calmodulin, and actin gene sequences. The phylogenetic analyses using the three genes clearly show that the taxa grouped separately from the known species and confirmed the phenotypic differences. Neosartorya denticulata is characterized by its unique denticulate ascospores with a prominent equatorial furrow; N. assulata by well developed flaps on the convex surface of the ascospores which in addition have two distinct equatorial crests and N. galapagensis by a funiculose colony morphology, short and narrow conidiophores and ascospores with two wide equatorial crests with a microtuberculate convex surface. Aspergillus turcosus can be distinguished by velvety, gray turquoise colonies and short, loosely columnar conidial heads. The four new taxa also have unique extrolite profiles, which contain the mycotoxins gliotoxin and viriditoxin in N. denticulate; apolar compounds provisionally named NEPS in N. assulata and gregatins in N. galapagensis. A. turcosus produced kotanins. N.denticulata sp. nov., N. assulata sp. nov., N. galapagensis sp. nov., and A. turcosus sp. nov. are described and illustrated

Addressing the evolution of automated user behaviour patterns by runtime model interpretation

The final publication is available at Springer via http://dx.doi.org/10.1007/s10270-013-0371-3The use of high-level abstraction models can facilitate and improve not only system development but also runtime system evolution. This is the idea of this work, in which behavioural models created at design time are also used at runtime to evolve system behaviour. These behavioural models describe the routine tasks that users want to be automated by the system. However, users¿ needs may change after system deployment, and the routine tasks automated by the system must evolve to adapt to these changes. To facilitate this evolution, the automation of the specified routine tasks is achieved by directly interpreting the models at runtime. This turns models into the primary means to understand and interact with the system behaviour associated with the routine tasks as well as to execute and modify it. 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