SysCall - Distinguishing heterozygous sites from systematic errors

http://bio.math.berkeley.edu/SysCall/

SysCall is a logistic regression based classifier.
Given a list of candidate heterozygous genomic locations and a sam file of sequenced reads SysCall classifies each genomic location as either a heterozygous site or a systematic error and outputs according lists, along with the assigned posterior probabilities.

The submitted manuscript describing SysCall can be found here and the lists of systematic errors reported in the paper are here .
The slides from a talk on SysCall given at the 2011 CSHL Meeting on The Biology of Genomes can be found here. 

Manual Click here to download the SysCall manual.

Paper
http://www.biomedcentral.com/1471-2105/12/451/

Subset of heat-shock transcription factors required for the early response of Arabidopsis to excess light

1. http://www.sciencedaily.com/releases/2013/08/130806132939.htm

2. http://www.pnas.org/content/early/2013/07/31/1311632110

Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia

http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2624.html

We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.

Interspecific Divergence of Transcription Networks along Lines of Genetic Variance inDrosophila: Dimensionality, Evolvability and Constraint

Change in gene expression is a major facilitator of phenotypic evolution. Understanding the evolutionary potential of gene expression requires taking into account complex systems of regulatory networks, the structure of which could potentially bias evolutionary trajectories. We analyzed the evolutionary potential and divergence of multigene expression in three well-characterized signaling pathways in Drosophila, the mitogen-activated protein kinase (MapK), the Toll, and the insulin receptor/Foxo (InR/Foxo or InR/TOR) pathways in a multivariate quantitative genetic framework. Gene expression data from a natural population of D. melanogaster were used to estimate the genetic variance–covariance matrices (G) for each network. Although most genes within each pathway exhibited significant genetic variance, the number of independent dimensions of multivariate genetic variance was fewer than the number of genes analyzed. However, for expression, the reduction in dimensionality was not as large as seen for other trait types such as morphology. We then tested whether gene expression divergence between D. melanogaster and an additional six species of the Drosophila genus was biased along the major axes of standing variation observed in D. melanogaster. In many cases, divergence was restricted to directions of phenotypic space harboring above average levels of genetic variance in D. melanogaster, indicating that genetic covariances between genes within pathways have biased interspecific divergence. We tested whether co-expression of genes in both sexes has also biased the pattern of divergence. Including cross-sex genetic covariances increased the degree to which divergence was biased along major axes of genetic variance, suggesting that the co-expression of genes in males and females can generate further constraints on divergence across the Drosophila phylogeny. In contrast to patterns seen for morphological traits in vertebrates, transcriptional constraints do not appear to break down as divergence time between species increases, instead they persist over tens of millions of years of divergence.

Genome-Wide Survey of Pseudogenes in 80 Fully Re-sequenced Arabidopsis thaliana Accessions

Pseudogenes (Ψs), including processed and non-processed Ψs, are ubiquitous genetic elements derived from originally functional genes in all studied genomes within the three kingdoms of life. However, systematic surveys of non-processed Ψs utilizing genomic information from multiple samples within a species are still rare. Here a systematic comparative analysis was conducted of Ψs within 80 fully re-sequenced Arabidopsis thalianaaccessions, and 7546 genes, representing ~28% of the genomic annotated open reading frames (ORFs), were found with disruptive mutations in at least one accession. The distribution of these Ψs on chromosomes showed a significantly negative correlation betweenΨs/ORFs and their local gene densities, suggesting a higher proportion of Ψs in gene desert regions, e.g. near centromeres. On the other hand, compared with the non-Ψ loci, even the intact coding sequences (CDSs) in the Ψ loci were found to have shorter CDS length, fewer exon number and lower GC content. In addition, a significant functional bias against the null hypothesis was detected in the Ψs mainly involved in responses to environmental stimuli and biotic stress as reported, suggesting that they are likely important for adaptive evolution to rapidly changing environments by pseudogenization to accumulate successive mutations.

MultiGeneBlast: Combined BLAST searches for operons and gene clusters

MultiGeneBlast is an open source tool for identification of homologs of multigene modules such as operons and gene clusters. It is based on a reformatting of the FASTA headers of NCBI GenBank protein entries, using which it can track down their source nucleotide and coordinates.

Oftentimes when studying such genetic loci, much can be learned from their evolutionary context. Furthermore, MultiGeneBlast can aid in the detection of such multigene parts for synthetic biology projects; a synthetic library of operons can be created based on its output to identify those operons whose function is closest to the one desired by the user.

This tool provides the opportunities to identify all homologous genomic regions by combining the results of single BlastP runs on each gene, and sorting genomic regions from any GenBank entry by the number of hits, synteny conservation and cumulative Blast bit score. The basic algorithm behind this was previously used in our antiSMASH software.
Additionally, architecture searches can be performed to find any genomic regions with Blast hits to any user-specified combination of amino acid sequences.

The tool comes with a pre-configured database containing the most recent version of all relevant GenBank divisions. Moreover, you can easily make your own databases from local files or online GenBank entries or divisions

http://multigeneblast.sourceforge.net/

Evolutionary Biology for the 21st Century

http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001466

Evolutionary Processes That Shape Genomic and Phenotypic Variation

The availability of genomic data from a remarkable range of species has allowed the alignment and comparison of whole genomes. These comparative approaches have been used to characterize the relative importance of fundamental evolutionary processes that cause genomic evolution and to identify particular regions of the genome that have experienced recent positive selection, recurrent adaptive evolution, or extreme sequence conservation[72]–[75]. Yet more recently, resequencing of additional individuals or populations is also allowing genome-wide population genetic analyses within species [76]–[82]. Such population-level comparisons will allow even more powerful study of the relative importance of particular evolutionary processes in molecular evolution as well as the identification of candidate genomic regions that are responsible for key evolutionary changes (e.g., sticklebacks [83], butterflies [84], Arabidopsis [85]). These data, combined with theoretical advances, should provide insight into long-standing questions such as the prevalence of balancing selection, the relative frequency of strong versus weak directional selection, the role of hybridization, and the importance of genetic drift. A key challenge will be to move beyond documenting the action of natural selection on the genome to understanding the importance of particular selective agents. For example, what proportion of selection on genomes results from adaptation to the abiotic environment, coevolution of species, sexual selection, or genetic conflict? Finally, as sequencing costs continue to drop and analytical tools improve, these same approaches may be applied to organisms that present intriguing evolutionary questions but were not tractable methodologically just a few years ago. The nonmodel systems of today may well become the model systems of tomorrow [86].

Understanding Biological Diversification

A major and urgent challenge is to improve knowledge of the identity and distribution of species globally. While we need to retain the traditional focus on phenotypes, powerful new capabilities to obtain and interpret both genomic and spatial data can and should revolutionize the science of biodiversity. Building on momentum from single-locus “barcoding" efforts, new genome-level data can build bridges from population biology to systematics [91]. By establishing a comprehensive and robust “Tree of Life," we will improve understanding of both the distribution of diversity and the nature and timing of the evolutionary processes that have shaped it.

DAVID and WebGESAT for pathway analysis

pathway analysis you can use: 

DAVID (http://david.abcc.ncifcrf.gov/), 

Gene Set Analysis Toolkit (http://bioinfo.vanderbilt.edu/webgestalt/)

Genomic consequences of transitions from cross- to self-fertilization on the efficacy of selection

Genomic consequences of transitions from cross- to self-fertilization on the efficacy of selection in three independently derived selfing plants

Background

Transitions from cross- to self-fertilization are associated with increased genetic drift rendering weakly selected mutations effectively neutral. The effect of drift is predicted to reduce selective constraints on amino acid sequences of proteins and relax biased codon usage. We investigated patterns of nucleotide variation to assess the effect of inbreeding on the accumulation of deleterious mutations in three independently evolved selfing plants. Using high-throughput sequencing, we assembled the floral transcriptomes of four individuals of Eichhornia(Pontederiaceae); these included one outcrosser and two independently derived selfers of E.paniculata, and E. paradoxa, a selfing outgroup. The dataset included ~8000 loci totalling ~3.5 Mb of coding DNA.

Results

Tests of selection were consistent with purifying selection constraining evolution of the transcriptome. However, we found an elevation in the proportion of non-synonymous sites that were potentially deleterious in the E. paniculata selfers relative to the outcrosser. Measurements of codon usage in high versus low expression genes demonstrated reduced bias in both E. paniculataselfers.

Conclusions

Our findings are consistent with a small reduction in the efficacy of selection on protein sequences associated with transitions to selfing, and reduced selection in selfers on synonymous changes that influence codon usage.

genetic diversity and the rate of recombination

Genome-wide analysis in chicken reveals that local levels of genetic diversity are mainly governed by the rate of recombination

Background

Polymorphism is key to the evolutionary potential of populations. Understanding which factors shape levels of genetic diversity within genomes forms a central question in evolutionary genomics and is of importance for the possibility to infer episodes of adaptive evolution from signs of reduced diversity. There is an on-going debate on the relative role of mutation and selection in governing diversity levels. This question is also related to the role of recombination because recombination is expected to indirectly affect polymorphism via the efficacy of selection. Moreover, recombination might itself be mutagenic and thereby assert a direct effect on diversity levels.

Results

We used whole-genome re-sequencing data from domestic chicken (broiler and layer breeds) and its wild ancestor (the red jungle fowl) to study the relationship between genetic diversity and several genomic parameters. We found that recombination rate had the largest effect on local levels of nucleotide diversity. The fact that divergence (a proxy for mutation rate) and recombination rate were negatively correlated argues against a mutagenic role of recombination. Furthermore, divergence had limited influence on polymorphism.

Conclusions

Overall, our results are consistent with a selection model, in which regions within a short distance from loci under selection show reduced polymorphism levels. This conclusion lends further support from the observations of strong correlations between intergenic levels of diversity and diversity at synonymous as well as non-synonymous sites. Our results also demonstrate differences between the two domestic breeds and red jungle fowl, where the domestic breeds show a stronger relationship between intergenic diversity levels and diversity at synonymous and non-synonymous sites. This finding, together with overall lower diversity levels in domesticates compared to red jungle fowl, seem attributable to artificial selection during domestication.

homologous and non-homologous recombination in genome evolution

Impact of homologous and non-homologous recombination in the genomic evolution of Escherichia coli

Genomicus: five genome browsers for comparative genomics in eukaryota

Genomicus (http://www.dyogen.ens.fr/genomicus/) is a database and an online tool that allows easy comparative genomic visualization in >150 eukaryote genomes. It provides a way to explore spatial information related to gene organization within and between genomes and temporal relationships related to gene and genome evolution. For the specific vertebrate phylum, it also provides access to ancestral gene order reconstructions and conserved non-coding elements information. We extended the Genomicus database originally dedicated to vertebrate to four new clades, including plants, non-vertebrate metazoa, protists and fungi. This visualization tool allows evolutionary phylogenomics analysis and exploration. Here, we describe the graphical modules of Genomicus and show how it is capable of revealing differential gene loss and gain, segmental or genome duplications and study the evolution of a locus through homology relationships.

Evolutionary Rate and Duplicability in the Arabidopsis thaliana Protein–Protein Interaction Network

http://gbe.oxfordjournals.org/content/4/12/1263.full

Genes show a bewildering variation in their patterns of molecular evolution, as a result of the action of different levels and types of selective forces. The factors underlying this variation are, however, still poorly understood. In the last decade, the position of proteins in the protein–protein interaction network has been put forward as a determinant factor of the evolutionary rate and duplicability of their encoding genes. This conclusion, however, has been based on the analysis of the limited number of microbes and animals for which interactome-level data are available (essentially, Escherichia coli, yeast, worm, fly, and humans). Here, we study, for the first time, the relationship between the position of proteins in the high-density interactome of a plant (Arabidopsis thaliana) and the patterns of molecular evolution of their encoding genes. We found that genes whose encoded products act at the center of the network are more evolutionarily constrained than those acting at the network periphery. This trend remains significant when potential confounding factors (gene expression level and breadth, duplicability, function, and length of the encoded products) are controlled for. Even though the correlation between centrality measures and rates of evolution is generally weak, for some functional categories, it is comparable in strength to (or even stronger than) the correlation between evolutionary rates and expression levels or breadths. In addition, genes encoding interacting proteins in the network evolve at relatively similar rates. Finally, Arabidopsis proteins encoded by duplicated genes are more highly connected than those encoded by singleton genes. This observation is in agreement with the patterns observed in humans, but in contrast with those observed in E. coli, yeast, worm, and fly (whose duplicated genes tend to act at the periphery of the network), implying that the relationship between duplicability and centrality inverted at least twice during eukaryote evolution. Taken together, these results indicate that the structure of the A. thaliana network constrains the evolution of its components at multiple levels.

Plant Resistance Gene -- R genes Wiki

PRGdb 2.0: towards a community-based database model for the analysis of R-genes in plants

http://prgdb.crg.eu/wiki/Main_Page

new model comparing two species

A New Isolation with Migration Model along Complete Genomes Infers Very Different Divergence Processes among Closely Related Great Ape Species

Relationship between nucleosome positioning and DNA methylation

http://www.nature.com/nature/journal/v466/n7304/full/nature09147.html

Nucleosomes compact and regulate access to DNA in the nucleus, and are composed of approximately 147 bases of DNA wrapped around a histone octamer^1, 2. Here we report a genome-wide nucleosome positioning analysis of Arabidopsis thaliana using massively parallel sequencing of mononucleosomes. By combining this data with profiles of DNA methylation at single base resolution, we identified 10-base periodicities in the DNA methylation status of nucleosome-bound DNA and found that nucleosomal DNA was more highly methylated than flanking DNA. These results indicate that nucleosome positioning influences DNA methylation patterning throughout the genome and that DNA methyltransferases preferentially target nucleosome-bound DNA. We also observed similar trends in human nucleosomal DNA, indicating that the relationships between nucleosomes and DNA methyltransferases are conserved. Finally, as has been observed in animals, nucleosomes were highly enriched on exons, and preferentially positioned at intron–exon and exon–intron boundaries. RNA polymerase II (Pol II) was also enriched on exons relative to introns, consistent with the hypothesis that nucleosome positioning regulates Pol II processivity. DNA methylation is also enriched on exons, consistent with the targeting of DNA methylation to nucleosomes, and suggesting a role for DNA methylation in exon definition.

Time scales of divergence andspeciation among natural populations and subspecies of Arabidopsis lyrata (Brassicaceae)

• Premise of the study: Plant populations that face new environments adaptand diverge simultaneously, and both processes leave footprints in theirgenetic diversity. Arabidopsis lyrata is an excellent species for studying these processes. Pairs of populations and subspecies of A. lyrata represent different stages of divergence. These populations are also known to be locally adapted and display various stages of emerging reproductive isolation.

• Methods: We used nucleotide diversity data from 19 loci to estimatedivergence times and levels of diversity among nine A. lyrata populations. Traditional distance-based methods and model-based clustering analysis were used to supplement pairwise coalescence-based analysis of divergence.

• Key results: Estimated divergence times varied from 130000 generations between North American and European subspecies to 39000 generations between central European and Scandinavian populations. In concordance with previous studies, the highest level of diversity was found in Central Europe and the lowest in North America and a diverged Russian Karhumäki population. Local adaptation among Northern and central European populations has emerged during the last 39000 generations. Populations that are reproductively isolated by prezygotic mechanisms have been separated for a longer time period of ∼70000 generations but still have shared nucleotide polymorphism.

• Conclusions: In A. lyrata, reproductively isolated populations started to diverge ∼70000 generations ago and more closely related, locally adapted populations have been separate lineages for ∼39000 generations. However, based on the posterior distribution of divergence times, the processes leading to reproductive isolation and local adaptation are likely to temporally coincide.

link ecologic niche models with intra-specific genetic variation

Climate envelope modelling reveals intraspecific relationships among flowering phenology, niche breadth and potential range size in Arabidopsis thaliana

http://evol-eco.blogspot.de/2012/05/putting-ecological-niche-models-to-good.html

Heterogeneity of the Transition/Transversion Ratio in Drosophila and Hominidae Genomes

Heterogeneity of the Transition/Transversion Ratio in Drosophila and Hominidae Genomes

1001 Proteomes of Arabidopsis thaliana

1001 Proteomes: A functional proteomics portal for the analysis of Arabidopsis thaliana accessions