Similar Levels of X-linked and Autosomal Nucleotide Variation in African and non-African populations of Drosophila melanogaster

<p>Abstract</p> <p>Background</p> <p>Levels of molecular diversity in Drosophila have repeatedly been shown to be higher in ancestral, African populations than in derived, non-African populations. This pattern holds for both coding and noncoding regions for a variety of molecular markers including single nucleotide polymorphisms and microsatellites. Comparisons of X-linked and autosomal diversity have yielded results largely dependent on population of origin.</p> <p>Results</p> <p>In an attempt to further elucidate patterns of sequence diversity in <it>Drosophila melanogaster</it>, we studied nucleotide variation at putatively nonfunctional X-linked and autosomal loci in sub-Saharan African and North American strains of <it>D. melanogaster</it>. We combine our experimental results with data from previous studies of molecular polymorphism in this species. We confirm that levels of diversity are consistently higher in African versus North American strains. The relative reduction of diversity for X-linked and autosomal loci in the derived, North American strains depends heavily on the studied loci. While the compiled dataset, comprised primarily of regions within or in close proximity to genes, shows a much more severe reduction of diversity on the X chromosome compared to autosomes in derived strains, the dataset consisting of intergenic loci located far from genes shows very similar reductions of diversities for X-linked and autosomal loci in derived strains. In addition, levels of diversity at X-linked and autosomal loci in the presumably ancestral African population are more similar than expected under an assumption of neutrality and equal numbers of breeding males and females.</p> <p>Conclusion</p> <p>We show that simple demographic scenarios under assumptions of neutral theory cannot explain all of the observed patterns of molecular diversity. We suggest that the simplest model is a population bottleneck that retains an ancestral female-biased sex ratio, coupled with higher rates of positive selection at X-linked loci in close proximity to genes specifically in derived, non-African populations.</p

Increased exposure to acute thermal stress is associated with a non-linear increase in recombination frequency and an independent linear decrease in fitness in Drosophila

Abstract Background Meiotic recombination rate has long been known to be phenotypically plastic. How plastic recombination evolves and is maintained remains controversial; though a leading model for the evolution of plastic recombination rests on the tenet that organismal fitness and recombination frequency are negatively correlated. Motivated by the mounting evidence that meiotic recombination frequencies increase in response to stress, here we test for a negative correlation between fitness and recombination frequency. Specifically, the fitness-associated recombination model (FAR) predicts that if stress increases meiotic recombination frequency, then increasing exposure to stressful conditions will yield an increasing magnitude of the recombinational response, while concomitantly decreasing fitness. Results We use heat shock as a stressor to test this prediction in Drosophila melanogaster. We find that increased exposure to heat shock conditions is associated with a non-linear increase in meiotic recombination frequency. We also find an independent effect of heat shock on organismal fitness, with fitness decreasing with increased duration of thermal stress. Conclusions Our results thus support the foundation of the FAR model for the evolution of plastic recombination. Our data also suggest that modulating recombination frequency is one mechanism by which organisms can rapidly respond to environmental cues and confer increased adaptive potential to their offspring

Increased exposure to acute thermal stress is associated with a non-linear increase in recombination frequency and an independent linear decrease in fitness in Drosophila

Background Meiotic recombination rate has long been known to be phenotypically plastic. How plastic recombination evolves and is maintained remains controversial; though a leading model for the evolution of plastic recombination rests on the tenet that organismal fitness and recombination frequency are negatively correlated. Motivated by the mounting evidence that meiotic recombination frequencies increase in response to stress, here we test for a negative correlation between fitness and recombination frequency. Specifically, the fitness-associated recombination model (FAR) predicts that if stress increases meiotic recombination frequency, then increasing exposure to stressful conditions will yield an increasing magnitude of the recombinational response, while concomitantly decreasing fitness. Results We use heat shock as a stressor to test this prediction in Drosophila melanogaster. We find that increased exposure to heat shock conditions is associated with a non-linear increase in meiotic recombination frequency. We also find an independent effect of heat shock on organismal fitness, with fitness decreasing with increased duration of thermal stress. Conclusions Our results thus support the foundation of the FAR model for the evolution of plastic recombination. Our data also suggest that modulating recombination frequency is one mechanism by which organisms can rapidly respond to environmental cues and confer increased adaptive potential to their offspring

Drosophila suzukii: the genetic footprint of a recent, world-wide invasion

Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. Here we investigate the genetic population structure of this invasive fruit fly, with a focus on the eastern United States. We sequenced six X-linked gene fragments from 246 individuals collected from a total of 12 populations. We examine patterns of genetic diversity within and between populations and explore alternative colonization scenarios using Approximate Bayesian Computation. Our results indicate high levels of nucleotide diversity in this species and suggest that the recent invasions of Europe and the continental United States are independent demographic events. More broadly speaking, our results highlight the importance of integrating population structure into demographic models, particularly when attempting to reconstruct invasion histories. Finally, our simulation results illustrate the general challenge of reconstructing invasion histories using genetic data and suggest that genome-level data are often required to distinguish among alternative demographic scenarios

Locus-Specific Decoupling of Base Composition Evolution at Synonymous Sites and Introns along the Drosophila melanogaster and Drosophila sechellia Lineages

Selection is thought to be partially responsible for patterns of molecular evolution at synonymous sites within numerous Drosophila species. Recently, “per-site” and likelihood methods have been developed to detect loci for which positive selection is a major component of synonymous site evolution. An underlying assumption of these methods, however, is a homogeneous mutation process. To address this potential shortcoming, we perform a complementary analysis making gene-by-gene comparisons of paired synonymous site and intron substitution rates toward and away from the nucleotides G and C because preferred codons are G or C ending in Drosophila. This comparison may reduce both the false-positive rate (due to broadscale heterogeneity in mutation) and false-negative rate (due to lack of power comparing small numbers of sites) of the per-site and likelihood methods. We detect loci with patterns of evolution suggestive of synonymous site selection pressures predominately favoring unpreferred and preferred codons along the Drosophila melanogaster and Drosophila sechellia lineages, respectively. Intron selection pressures do not appear sufficient to explain all these results as the magnitude of the difference in synonymous and intron evolution is dependent on recombination environment and chromosomal location in a direction supporting the hypothesis of selectively driven synonymous fixations. This comparison identifies 101 loci with an apparent switch in codon preference between D. melanogaster and D. sechellia, a pattern previously only observed at the Notch locus

Allelic Expression Changes in Medaka (Oryzias latipes) Hybrids between Inbred Strains Derived from Genetically Distant Populations

Variations in allele expressions between genetically distant populations are one of the most important factors which affects their morphological and physiological variations. These variations are caused by natural mutations accumulated in their habitats. It has been reported that allelic expression differences in the hybrids of genetically distant populations are different from parental strains. In that case, there is a possibility that allelic expression changes lead to novel phenotypes in hybrids. Based on genomic information of the genetically distant populations, quantification and comparison of allelic expression changes make importance of regulatory sequences (cis-acting factors) or upstream regulatory factors (trans-acting modulators) for these changes clearer. In this study, we focused on two Medaka inbred strains, Hd-rR and HNI, derived from genetically distant populations and their hybrids. They are highly polymorphic and we can utilize whole-genome information. To analyze allelic expression changes, we established a method to quantify and compare allele-specific expressions of 11 genes between the parental strains and their reciprocal hybrids. In intestines of reciprocal hybrids, allelic expression was either similar or different in comparison with the parental strains. Total expressions in Hd-rR and HNI were tissue-dependent in the case of HPRT1, with high up-regulation of Hd-rR allele expression in liver. The proportion of genes with differential allelic expression in Medaka hybrids seems to be the same as that in other animals, despite the high SNP rate in the genomes of the two inbred strains. It is suggested that each tissue of the strain difference in trans-acting modulators is more important than polymorphisms in cis-regulatory sequences in producing the allelic expression changes in reciprocal hybrids

New tools for detecting latent tuberculosis infection: evaluation of RD1-specific long-term response

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma (IFN-γ) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRAs results that cannot be attributed to prior Bacille Calmètte Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-γ response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT-IT).</p> <p>Methods</p> <p>The study population included 106 healthy TST⁺individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to <it>M. tuberculosis </it>(TST^-, QFT-IT^-) and 29 subjects with cured pulmonary TB were enrolled. IFN-γ whole blood response to RD1 proteins and QFT-IT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-γ response (7-day) to RD1 proteins in diluted whole blood was performed.</p> <p>Results</p> <p>Among the enrolled TST⁺subjects with suspected LTBI, 70/106 (66.0%) responded to QFT-IT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-IT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-γ levels in cured TB patients compared to healthy controls (p < 0.006). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT-IT, a long term response to RD1 proteins was detected in 11 subjects (30.6%).</p> <p>Conclusion</p> <p>These results indicate that IFN-γ long-term response to <it>M. tuberculosis </it>RD1 antigens may be used to detect past infection with <it>M. tuberculosis </it>and may help to identify additional individuals with LTBI who resulted negative in the short-term tests. These data may provide useful information for improving immunodiagnostic tests for tuberculosis infection, especially in individuals at high risk for active TB.</p

Minor shift in background substitutional patterns in the Drosophila saltans and willistoni lineages is insufficient to explain GC content of coding sequences

BACKGROUND: Several lines of evidence suggest that codon usage in the Drosophila saltans and D. willistoni lineages has shifted towards a less frequent use of GC-ending codons. Introns in these lineages show a parallel shift toward a lower GC content. These patterns have been alternatively ascribed to either a shift in mutational patterns or changes in the definition of preferred and unpreferred codons in these lineages. RESULTS AND DISCUSSION: To gain additional insight into this question, we quantified background substitutional patterns in the saltans/willistoni group using inactive copies of a novel, Q-like retrotransposable element. We demonstrate that the pattern of background substitutions in the saltans/willistoni lineage has shifted to a significant degree, primarily due to changes in mutational biases. These differences predict a lower equilibrium GC content in the genomes of the saltans/willistoni species compared with that in the D. melanogaster species group. The magnitude of the difference can readily account for changes in intronic GC content, but it appears insufficient to explain changes in codon usage within the saltans/willistoni lineage. CONCLUSION: We suggest that the observed changes in codon usage in the saltans/willistoni clade reflects either lineage-specific changes in the definitions of preferred and unpreferred codons, or a weaker selective pressure on codon bias in this lineage

Origin and spread of human mitochondrial DNA haplogroup U7

Human mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (~16–19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that – analysed alongside 100 published ones – enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East. The earlier one began prior to the Holocene (~11.5 thousand years ago) towards South Asia, while the later dispersal took place more recently towards Mediterranean Europe during the Neolithic (~8 thousand years ago). These findings imply that the carriers of haplogroup U7 spread to South Asia and Europe before the suggested Bronze Age expansion of Indo-European languages from the Pontic-Caspian Steppe region

Diseases of the rich? The social patterning of hypertension in six low- and middle-income countries

This paper identifies a general perception among development policymakers that health conditions such as hypertension and other non-communicable diseases (NCDs) disproportionately affect privileged socioeconomic groups. The paper argues that this framing of the issue is derived more from established discourses and institutional dynamics than from evidence. The paper then assesses the validity of this view, with reference to the social patterning of hypertension in China, Ghana, India, Mexico, the Russian Federation and South Africa. Using data for adults aged 50+ from the WHO Survey of Ageing and Adult Health, it finds the social patterning of hypertension prevalence varies markedly between the study countries, but that hypertension awareness and control rates are generally lower for less-advantaged groups. This reveals a need to challenge misleading representations of NCD pandemics and for interventions that specifically target the poor