Background Any DNA sequence is a result of compromise between the selection and mutation pressures exerted on it during evolution. It is difficult to estimate the relative influence of each of these pressures on the rate of accumulation of substitutions. However, it is important to discriminate between the effect of mutations, and the effect of selection, when studying the phylogenic relations between taxa. Results We have tested in computer simulations, and analytically, the available substitution matrices for many genomes, and we have found that DNA strands in equilibrium under mutational pressure have unique feature: the fraction of each type of nucleotide is linearly dependent on the time needed for substitution of half of nucleotides of a given type, with a correlation coefficient close to 1. Substitution matrices found for sequences under selection pressure do not have this property. A substitution matrix for the leading strand of the Borrelia burgdorferi genome, having reached equilibrium in computer simulation, gives a DNA sequence with nucleotide composition and asymmetry corresponding precisely to the third positions in codons of protein coding genes located on the leading strand. Conclusions Parameters of mutational pressure allow us to count DNA composition in equilibrium with this mutational pressure. Comparing any real DNA sequence with the sequence in equilibrium it is possible to estimate the distance between these sequences, which could be used as a measure of the selection pressure. Furthermore, the parameters of the mutational pressure enable direct estimation of the relative mutation rates in any DNA sequence in the studied genome.

Background Earlier methods for detecting major genes responsible for a quantitative trait rely critically upon a well-structured pedigree in which the segregation pattern of genes exactly follow Mendelian inheritance laws. However, for many outcrossing species, such pedigrees are not available and genes also display population properties. Results In this paper, a hierarchical statistical model is proposed to monitor the existence of a major gene based on its segregation and transmission across two successive generations. The model is implemented with an EM algorithm to provide maximum likelihood estimates for genetic parameters of the major locus. This new method is successfully applied to identify an additive gene having a large effect on stem height growth of aspen trees. The estimates of population genetic parameters for this major gene can be generalized to the original breeding population from which the parents were sampled. A simulation study is presented to evaluate finite sample properties of the model. Conclusions A hierarchical model was derived for detecting major genes affecting a quantitative trait based on progeny tests of outcrossing species. The new model takes into account the population genetic properties of genes and is expected to enhance the accuracy, precision and power of gene detection.

To assess whether the pattern of high rates of genome rearrangement, with a bias towards within-chromosome events is true of nematodes in general, genome sequence was used to compare the model Caenorhabditis elegans and the filarial parasite Brugia malayi. It is suggested that intrachromosomal rearrangement is a major force driving chromosomal organization in nematodes.

Wildlife populations are increasingly threatened by human activities. Most studies, however, are often short in duration or do not encompass the large spatial extent necessary to measure the potential effects of human activities on population vital rates. Furthermore, the life history features of species with high fecundity and excellent dispersal capabilities can act as buffers against the potential negative effects of human activities on their populations. We used a 30-year dataset of genetic samples from gray wolves (Canis lupus) in Alaska, USA to examine genetic connectivity and diversity between National Park units separated by a region with recurrent human-caused mortality. We found that the 2 protected populations were genetically similar and that dispersal events occurred between them even though they are >450 km apart. We posit that intact ecosystems and a history of continuous distribution of wolves surrounding the affected regions likely maintained the genetic connectivity of wolves in the 2 protected areas.

Background Gene duplications have a major role in the evolution of new biological functions. Theoretical studies often assume that a duplication per se is selectively neutral and that, following a duplication, one of the gene copies is freed from purifying (stabilizing) selection, which creates the potential for evolution of a new function. Results In search of systematic evidence of accelerated evolution after duplication, we used data from 26 bacterial, six archaeal, and seven eukaryotic genomes to compare the mode and strength of selection acting on recently duplicated genes (paralogs) and on similarly diverged, unduplicated orthologous genes in different species. We find that the ratio of nonsynonymous to synonymous substitutions (Kn/Ks) in most paralogous pairs is <<1 and that paralogs typically evolve at similar rates, without significant asymmetry, indicating that both paralogs produced by a duplication are subject to purifying selection. This selection is, however, substantially weaker than the purifying selection affecting unduplicated orthologs that have diverged to the same extent as the analyzed paralogs. Most of the recently duplicated genes appear to be involved in various forms of environmental response; in particular, many of them encode membrane and secreted proteins. Conclusions The results of this analysis indicate that recently duplicated paralogs evolve faster than orthologs with the same level of divergence and similar functions, but apparently do not experience a phase of neutral evolution. We hypothesize that gene duplications that persist in an evolving lineage are beneficial from the time of their origin, due primarily to a protein dosage effect in response to variable environmental conditions; duplications are likely to give rise to new functions at a later phase of their evolution once a higher level of divergence is reached.

Background Identification of co-regulated genes is essential for elucidating transcriptional regulatory networks and the function of uncharacterized genes. Although co-regulated genes should have at least one common sequence element, it is generally difficult to identify these genes from the presence of this element because it is very easily obscured by noise. To overcome this problem, we used conserved information from three closely related species: Bacillus subtilis, B. halodurans and B. stearothermophilus. Results Even though such species have a limited number of clearly orthologous genes, we obtained 1,884 phylogenetically conserved elements from the upstream intergenic regions of 1,568 B. subtilis genes. Similarity between these elements was used to cluster these genes. No other a priori knowledge on genes and elements was used. We could identify some genes known or suggested to be regulated by a common transcription factor as well as genes regulated by a common attenuation effector. Conclusions We confirmed that our method generates relatively few false positives in clusters with higher scores and that general elements such as -35/-10 boxes and Shine-Dalgarno sequence are not major obstacles. Moreover, we identified some plausible additional members of groups of known co-regulated genes. Thus, our approach is promising for exploring potentially co-regulated genes.

Comparative genomics provides at least three methods for identifying functional links between genes: examination of phylogenetic distributions, analysis of conserved proximity and observations of fusions of genes into a multidomain gene in another organism. We show that the functional networks obtained by applying these methods have different topologies and that the information they provide is largely additive. In particular, the combined networks of functional links contain an average of 57% of an organism's complete genetic complement, uncover substantial portions of known pathways, and suggest the function of previously unannotated genes. In addition, the combined networks are qualitatively different from the networks obtained using individual methods.

Background In most organisms proper reductional chromosome segregation during meiosis I is strongly correlated with the presence of crossover recombination structures (chiasmata); recombination deficient mutants lack crossovers and suffer meiosis I nondisjunction. We report that these functions are separable in the fission yeast Schizosaccharomyces pombe. Results Intron mapping and expression studies confirmed that Rec12 is a member of the Spo11/Top6A topoisomerase family required for the formation of meiotic dsDNA breaks and recombination. rec12-117, rec12-D15 (null), and rec12-Y98F (active site) mutants lacked most crossover recombination and chromosomes segregated abnormally to generate aneuploid meiotic products. Since S. pombe contains only three chromosome pairs, many of those aneuploid products were viable. The types of aberrant chromosome segregation were inferred from the inheritance patterns of centromere linked markers in diploid meiotic products. The rec12-117 and rec12-D15 mutants manifest segregation errors during both meiosis I and meiosis II. Remarkably, the rec12-Y98F (active site) mutant exhibited essentially normal meiosis I segregation patterns, but still exhibited meiosis II segregation errors. Conclusions Rec12 is a 345 amino acid protein required for most crossover recombination and for chiasmatic segregation of chromosomes during meiosis I. Rec12 also participates in a backup distributive (achiasmatic) system of chromosome segregation during meiosis I. In addition, catalytically-active Rec12 mediates some signal that is required for faithful equational segregation of chromosomes during meiosis II.

Background Recombinant inbred (RI) strains of mice are an important resource used to map and analyze complex traits. They have proved particularly effective in multidisciplinary genetic studies. Widespread use of RI strains has been hampered by their modest numbers and by the difficulty of combining results derived from different RI sets. Results We have increased the density of typed microsatellite markers two- to five-fold in each of several major RI sets that share C57BL/6 as a parental strain (AXB, BXA, BXD, BXH and CXB). A common set of 490 markers was genotyped in just over 100 RI strains. Genotypes of around 1,100 additional microsatellites in one or more RI sets were generated, collected and checked for errors. Consensus RI maps that integrate genotypes of approximately 1,600 microsatellite loci were assembled. The genomes of individual strains typically incorporate 45-55 recombination breakpoints. The collected RI set - termed the BXN set - contains approximately 5,000 breakpoints. The distribution of recombinations approximates a Poisson distribution and distances between breakpoints average about 0.5 centimorgans (cM). Locations of most breakpoints have been defined with a precision of < 2 cM. Genotypes deviate from Hardy-Weinberg equilibrium in only a small number of intervals. Conclusions Consensus maps derived from RI strains conform almost exactly to theoretical expectation and are close to the length predicted by the Haldane-Waddington equation (x3.6 for a 2-3 cM interval between markers). Non-syntenic associations between different chromosomes introduce predictable distortions in quantitative trait locus (QTL) datasets that can be partly corrected using two-locus correlation matrices.