Re-analysis of the larval testis data on meiotic sex chromosome inactivation revealed evidence for tissue-specific gene expression related to the drosophila X chromosome

<p>Abstract</p> <p>Background</p> <p>Meiotic sex chromosome inactivation (MSCI) during spermatogenesis has been proposed as one of the evolutionary driving forces behind both the under-representation of male-biased genes on, and the gene movement out of, the X chromosome in <it>Drosophila</it>. However, the relevance of MSCI in shaping sex chromosome evolution is controversial. Here we examine two aspects of a recent study on testis gene expression (Mikhaylova and Nurminsky, <it>BMC Biol </it>2011, <b>9:</b>29) that failed to support the MSCI in <it>Drosophila</it>. First, Mikhaylova and Nurminsky found no differences between X-linked and autosomal genes based on the transcriptional profiling of the early testis development, and thus concluded that MSCI does not occur in <it>D. melanogaster</it>. Second, they also analyzed expression data from several <it>D. melanogaster </it>tissues and concluded that under-representation on the X chromosome is not an exclusive property of testis-biased genes, but instead, a general property of tissue-specific genes.</p> <p>Results</p> <p>By re-analyzing the Mikhaylova and Nurminsky's testis data and the expression data on several <it>D. melanogaster </it>tissues, we made two major findings that refuted their original claims. First, the developmental testis data has generally greater experimental error than conventional analyses, which reduced significantly the power to detect chromosomal differences in expression. Nevertheless, our re-analysis observed significantly lower expression of the X chromosome in the genomic transcriptomes of later development stages of the testis, which is consistent with the MSCI hypothesis. Second, tissue-specific genes are also in general enriched with genes more expressed in testes than in ovaries, that is testis-biased genes. By completely excluding from the analyses the testis-biased genes, which are known to be under-represented in the X, we found that all the other tissue-specific genes are randomly distributed between the X chromosome and the autosomes.</p> <p>Conclusions</p> <p>Our findings negate the original study of Mikhaylova and Nurminsky, which concluded a lack of MSCI and generalized the pattern of paucity in the X chromosome for tissue-specific genes in <it>Drosophila</it>. Therefore, MSCI and other selection-based models such as sexual antagonism, dosage compensation, and meiotic-drive continue to be viable models as driving forces shaping the genomic distribution of male-related genes in <it>Drosophila</it>.</p

Population transcriptomics of Drosophila melanogaster females

<p>Abstract</p> <p>Background</p> <p>Variation at the level of gene expression is abundant in natural populations and is thought to contribute to the adaptive divergence of populations and species. Gene expression also differs considerably between males and females. Here we report a microarray analysis of gene expression variation among females of 16 <it>Drosophila </it><it>melanogaster </it>strains derived from natural populations, including eight strains from the putative ancestral range in sub-Saharan Africa and eight strains from Europe. Gene expression variation among males of the same strains was reported previously.</p> <p>Results</p> <p>We detected relatively low levels of expression polymorphism within populations, but much higher expression divergence between populations. A total of 569 genes showed a significant expression difference between the African and European populations at a false discovery rate of 5%. Genes with significant over-expression in Europe included the insecticide resistance gene <it>Cyp6g1</it>, as well as genes involved in proteolysis and olfaction. Genes with functions in carbohydrate metabolism and vision were significantly over-expressed in the African population. There was little overlap between genes expressed differently between populations in females and males.</p> <p>Conclusions</p> <p>Our results suggest that adaptive changes in gene expression have accompanied the out-of-Africa migration of <it>D. melanogaster</it>. Comparison of female and male expression data indicates that the vast majority of genes differing in expression between populations do so in only one sex and suggests that most regulatory adaptation has been sex-specific.</p

Evolutionary analysis of mitochondrially encoded proteins of toad-headed lizards, Phrynocephalus, along an altitudinal gradient.

BACKGROUND: Animals living at high altitude must adapt to environments with hypoxia and low temperatures, but relatively little is known about underlying genetic changes. Toad-headed lizards of the genus Phrynocephalus cover a broad altitudinal gradient of over 4000 m and are useful models for studies of such adaptive responses. In one of the first studies to have considered selection on mitochondrial protein-coding regions in an ectothermic group distributed over such a wide range of environments, we analysed nineteen complete mitochondrial genomes from all Chinese Phrynocephalus (including eight genomes sequenced for the first time). Initial analyses used site and branch-site model (program: PAML) approaches to examine nonsynonymous: synonymous substitution rates across the mtDNA tree. RESULTS: Ten positively selected sites were discovered, nine of which corresponded to subunits ND2, ND3, ND4, ND5, and ND6 within the respiratory chain enzyme mitochondrial Complex I (NADH Coenzyme Q oxidoreductase). Four of these sites showed evidence of general long-term selection across the group while the remainder showed evidence of episodic selection across different branches of the tree. Some of these branches corresponded to increases in altitude and/or latitude. Analyses of physicochemical changes in protein structures revealed that residue changes at sites that were under selection corresponded to major functional differences. Analyses of coevolution point to coevolution of selected sites within the ND4 subunit, with key sites associated with proton translocation across the mitochondrial membrane. CONCLUSIONS: Our results identify mitochondrial Complex I as a target for environment-mediated selection in this group of lizards, a complex that frequently appears to be under selection in other organisms. This makes these lizards good candidates for more detailed future studies of molecular evolution

Evolutionary Patterns of the Mitochondrial Genome in Metazoa: Exploring the Role of Mutation and Selection in Mitochondrial Protein–Coding Genes

The mitochondrial genome is a fundamental component of the eukaryotic domain of life, encoding for several important subunits of the respiratory chain, the main energy production system in cells. The processes by means of which mitochondrial DNA (mtDNA) replicates, expresses itself and evolves have been explored over the years, although various aspects are still debated. In this review, we present several key points in modern research on the role of evolutionary forces in affecting mitochondrial genomes in Metazoa. In particular, we assemble the main data on their evolution, describing the contributions of mutational pressure, purifying, and adaptive selection, and how they are related. We also provide data on the evolutionary fate of the mitochondrial synonymous variation, related to the nonsynonymous variation, in comparison with the pattern detected in the nucleus

Divergence across mitochondrial genomes of sympatric members of the Schistosoma indicum group and clues into the evolution of Schistosoma spindale

Schistosoma spindale and Schistosoma indicum are ruminant-infecting trematodes of the Schistosoma indicum group that are widespread across Southeast Asia. Though neglected, these parasites can cause major pathology and mortality to livestock leading to significant welfare and socio-economic issues, predominantly amongst poor subsistence farmers and their families. Here we used mitogenomic analysis to determine the relationships between these two sympatric species of schistosome and to characterise S. spindale diversity in order to identify possible cryptic speciation. The mitochondrial genomes of S. spindale and S. indicum were assembled and genetic analyses revealed high levels of diversity within the S. indicum group. Evidence of functional changes in mitochondrial genes indicated adaptation to environmental change associated with speciation events in S. spindale around 2.5 million years ago. We discuss our results in terms of their theoretical and applied implications

The effects of acute tryptophan depletion on costly information sampling: impulsivity or aversive processing?

RATIONALE: The neurotransmitter serotonin (5-HT) has been implicated in both aversive processing and impulsivity. Reconciling these accounts, recent studies have demonstrated that 5-HT is important for punishment-induced behavioural inhibition. These studies focused on situations where actions lead directly to punishments. However, decision-making often involves making tradeoffs between small 'local' costs and larger 'global' losses. OBJECTIVE: We aimed to distinguish whether 5-HT promotes avoidance of local losses, global losses, or both, in contrast to an overall effect on reflection impulsivity. We further examined the influence of individual differences in sub-clinical depression, anxiety and impulsivity on global and local loss avoidance. METHODS: Healthy volunteers (N = 21) underwent an acute tryptophan depletion procedure in a double-blind, placebo-controlled crossover design. We measured global and local loss avoidance in a decision-making task where subjects could sample information at a small cost to avoid making incorrect decisions, which resulted in large losses. RESULTS: Tryptophan depletion removed the suppressive effects of small local costs on information sampling behaviour. Sub-clinical depressive symptoms produced effects on information sampling similar to (but independent from) those of tryptophan depletion. Dispositional anxiety was related to global loss avoidance. However, trait impulsivity was unrelated to information sampling. CONCLUSIONS: The current findings are consistent with recent theoretical work that characterises 5-HT as pruning a tree of potential decisions, eliminating options expected to lead to aversive outcomes. Our results extend this account by proposing that 5-HT promotes reflexive avoidance of relatively immediate aversive outcomes, potentially at the expense of more globally construed future losses

IL-2 Immunotherapy to Recently HIV-1 Infected Adults Maintains the Numbers of IL-17 Expressing CD4+ T (TH17) Cells in the Periphery

Little is known about the manipulation of IL-17 producing CD4+ T cells (TH17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of TH17 cells declined, while counts of TH17 cells did not change due to an expansion of the CD4+ naïve T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of TH17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV-1 Gag

Effects of Ploidy and Recombination on Evolution of Robustness in a Model of the Segment Polarity Network

Many genetic networks are astonishingly robust to quantitative variation, allowing these networks to continue functioning in the face of mutation and environmental perturbation. However, the evolution of such robustness remains poorly understood for real genetic networks. Here we explore whether and how ploidy and recombination affect the evolution of robustness in a detailed computational model of the segment polarity network. We introduce a novel computational method that predicts the quantitative values of biochemical parameters from bit sequences representing genotype, allowing our model to bridge genotype to phenotype. Using this, we simulate 2,000 generations of evolution in a population of individuals under stabilizing and truncation selection, selecting for individuals that could sharpen the initial pattern of engrailed and wingless expression. Robustness was measured by simulating a mutation in the network and measuring the effect on the engrailed and wingless patterns; higher robustness corresponded to insensitivity of this pattern to perturbation. We compared robustness in diploid and haploid populations, with either asexual or sexual reproduction. In all cases, robustness increased, and the greatest increase was in diploid sexual populations; diploidy and sex synergized to evolve greater robustness than either acting alone. Diploidy conferred increased robustness by allowing most deleterious mutations to be rescued by a working allele. Sex (recombination) conferred a robustness advantage through “survival of the compatible”: those alleles that can work with a wide variety of genetically diverse partners persist, and this selects for robust alleles

Midlife managerial experience is linked to late life hippocampal morphology and function

An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p  <  0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p  <  0.001). Finally, hierarchical regression modelling substantiated this double dissociation