Efficient algorithms for reconstructing gene content by co-evolution

<p>Abstract</p> <p>Background</p> <p>In a previous study we demonstrated that co-evolutionary information can be utilized for improving the accuracy of ancestral gene content reconstruction. To this end, we defined a new computational problem, the Ancestral Co-Evolutionary (ACE) problem, and developed algorithms for solving it.</p> <p>Results</p> <p>In the current paper we generalize our previous study in various ways. First, we describe new efficient computational approaches for solving the ACE problem. The new approaches are based on reductions to classical methods such as linear programming relaxation, quadratic programming, and min-cut. Second, we report new computational hardness results related to the ACE, including practical cases where it can be solved in polynomial time.</p> <p>Third, we generalize the ACE problem and demonstrate how our approach can be used for inferring parts of the genomes of <it>non-ancestral</it> organisms. To this end, we describe a heuristic for finding the portion of the genome ('dominant set’) that can be used to reconstruct the rest of the genome with the lowest error rate. This heuristic utilizes both evolutionary information and co-evolutionary information.</p> <p>We implemented these algorithms on a large input of the ACE problem (95 unicellular organisms, 4,873 protein families, and 10, 576 of co-evolutionary relations), demonstrating that some of these algorithms can outperform the algorithm used in our previous study. In addition, we show that based on our approach a ’dominant set’ cab be used reconstruct a major fraction of a genome (up to 79%) with relatively low error-rate (<it>e.g.</it> 0.11). We find that the ’dominant set’ tends to include metabolic and regulatory genes, with high evolutionary rate, and low protein abundance and number of protein-protein interactions.</p> <p>Conclusions</p> <p>The <it>ACE</it> problem can be efficiently extended for inferring the genomes of organisms that exist today. In addition, it may be solved in polynomial time in many practical cases. Metabolic and regulatory genes were found to be the most important groups of genes necessary for reconstructing gene content of an organism based on other related genomes.</p

Complex Interplay of Evolutionary Forces in the ladybird Homeobox Genes of Drosophila melanogaster

Tandemly arranged paralogous genes lbe and lbl are members of the Drosophila NK homeobox family. We analyzed population samples of Drosophila melanogaster from Africa, Europe, North and South America, and single strains of D. sechellia, D. simulans, and D. yakuba within two linked regions encompassing partial sequences of lbe and lbl. The evolution of lbe and lbl is highly constrained due to their important regulatory functions. Despite this, a variety of forces have shaped the patterns of variation in lb genes: recombination, intragenic gene conversion and natural selection strongly influence background variation created by linkage disequilibrium and dimorphic haplotype structure. The two genes exhibited similar levels of nucleotide diversity and positive selection was detected in the noncoding regions of both genes. However, synonymous variability was significantly higher for lbe: no nonsynonymous changes were observed in this gene. We argue that balancing selection impacts some synonymous sites of the lbe gene. Stability of mRNA secondary structure was significantly different between the lbe (but not lbl) haplotype groups and may represent a driving force of balancing selection in epistatically interacting synonymous sites. Balancing selection on synonymous sites may be the first, or one of a few such observations, in Drosophila. In contrast, recurrent positive selection on lbl at the protein level influenced evolution at three codon sites. Transcription factor binding-site profiles were different for lbe and lbl, suggesting that their developmental functions are not redundant. Combined with our previous results on nucleotide variation in esterase and other homeobox genes, these results suggest that interplay of balancing and directional selection may be a general feature of molecular evolution in Drosophila and other eukaryote genomes

Recombinational Landscape and Population Genomics of Caenorhabditis elegans

Recombination rate and linkage disequilibrium, the latter a function of population genomic processes, are the critical parameters for mapping by linkage and association, and their patterns in Caenorhabditis elegans are poorly understood. We performed high-density SNP genotyping on a large panel of recombinant inbred advanced intercross lines (RIAILs) of C. elegans to characterize the landscape of recombination and, on a panel of wild strains, to characterize population genomic patterns. We confirmed that C. elegans autosomes exhibit discrete domains of nearly constant recombination rate, and we show, for the first time, that the pattern holds for the X chromosome as well. The terminal domains of each chromosome, spanning about 7% of the genome, exhibit effectively no recombination. The RIAILs exhibit a 5.3-fold expansion of the genetic map. With median marker spacing of 61 kb, they are a powerful resource for mapping quantitative trait loci in C. elegans. Among 125 wild isolates, we identified only 41 distinct haplotypes. The patterns of genotypic similarity suggest that some presumed wild strains are laboratory contaminants. The Hawaiian strain, CB4856, exhibits genetic isolation from the remainder of the global population, whose members exhibit ample evidence of intercrossing and recombining. The population effective recombination rate, estimated from the pattern of linkage disequilibrium, is correlated with the estimated meiotic recombination rate, but its magnitude implies that the effective rate of outcrossing is extremely low, corroborating reports of selection against recombinant genotypes. Despite the low population, effective recombination rate and extensive linkage disequilibrium among chromosomes, which are techniques that account for background levels of genomic similarity, permit association mapping in wild C. elegans strains

Global connectivity and ethnic fractionalization: new frontiers of global trade agenda

International trade is an exchange that involves goods and services between countries or international territories, and it signifies a significant share of gross domestic product. Global trading provides opportunities for the country to show its products and services through imports and exports. While this international event gives rise to a world economy, global connectivity and ethnic heterogeneity play a significant role. This paper aims to determine whether the ruggedness of a country supports international trade and global connectivity and whether the ruggedness of ethnic heterogeneity supports global trading. This paper uses the non-experimental quantitative inferential design utilizing Fractal Analysis to determine the self-similarity of countries engaging in international trade in terms of their global connectivity index and ethnic fractionalization. The International Trade data provided by the World Integrated Trade Solutions and the Global Connectivity Index (GCI) data through Huawei Technologies are plotted in a histogram through Minitab Software to determine the fractality and further apply exponential logarithm. Study shows that global connectivity and ethnic fractionalization induce the fractal characteristics of the countries’ international trade ruggedness. Specific to the behavior is that countries with very high international trade also behave similarly with high global connectivity and very low ethnicity fractionalization. As countries sustain a progressive economic stance, their societies maintain very few ethnic groups to promote social cohesion, much less conflict created by many ethnic groups that vary in their concerns. This paper further explains that only countries with digital economic competitiveness and cultural homogeneity survive robust international trade

Prevalence of extended-spectrum beta-lactamase producing Escherichia coli in community-onset urinary tract infections in France in 2013

International audienceObjectives : We sought to assess the importance of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae in urinary tract infections in outpatients in France.Methods : Retrospective laboratory based survey analysing susceptibility patterns of Escherichia coli and Klebsiella pneumoniae isolates providing from urines collected from outpatients during three months in 2013.Results : 499 laboratories collected data on 51,643 E. coli and 3,495 K. pneumoniae isolates. The overall proportion of ESBL-producing E. coli was 3.3%. The proportion was higher for males (4.8%) than for females (3.0%) and increased with age: 2% for patients 80 years. More than 95% of isolates we susceptible to cefixime, fosfomycin, and nitrofurantoin. In nursing homes, the ESBL-producing E. coli proportion was 12.1%. For K. pneumoniae, the proportion of ESBL-positive isolates was 6.6%, and this proportion increased with age. Data from 2010 collected from a subset of the network showed that the ESBL-producing E. coli proportion was 2.0%.Conclusion : ESBL-producing isolates were rather frequent in urines in French outpatients in 2013. Males and persons residing in nursing homes were at higher risk of ESBL-positive infection. Despite the increase in ESBL-positive isolates, the susceptibility to antibiotics used to treat cystitis remains high

Full-genome evolutionary histories of selfing, splitting, and selection in Caenorhabditis

The nematode Caenorhabditis briggsae is a model for comparative developmental evolution with C. elegans. Worldwide collections of C. briggsae have implicated an intriguing history of divergence among genetic groups separated by latitude, or by restricted geography, that is being exploited to dissect the genetic basis to adaptive evolution and reproductive incompatibility; yet, the genomic scope and timing of population divergence is unclear. We performed high-coverage whole-genome sequencing of 37 wild isolates of the nematode C. briggsae and applied a pairwise sequentially Markovian coalescent (PSMC) model to 703 combinations of genomic haplotypes to draw inferences about population history, the genomic scope of natural selection, and to compare with 40 wild isolates of C. elegans. We estimate that a diaspora of at least six distinct C. briggsae lineages separated from one another approximately 200,000 generations ago, including the "Temperate" and "Tropical" phylogeographic groups that dominate most samples worldwide. Moreover, an ancient population split in its history approximately 2 million generations ago, coupled with only rare gene flow among lineage groups, validates this system as a model for incipient speciation. Low versus high recombination regions of the genome give distinct signatures of population size change through time, indicative of widespread effects of selection on highly linked portions of the genome owing to extreme inbreeding by self-fertilization. Analysis of functional mutations indicates that genomic context, owing to selection that acts on long linkage blocks, is a more important driver of population variation than are the functional attributes of the individually encoded genes