Influence of a small fraction of individuals with enhanced mutations on a population genetic pool

Computer simulations of the Penna ageing model suggest that already a small fraction of births with enhanced number of new mutations can negatively influence the whole population.Comment: 10 pages including 6 figures; draf

Genetic recombination and molecular evolution

Reduced rates of genetic recombination are often associated with reduced genetic variability and levels of adaptation. Several different evolutionary processes, collectively known as Hill–Robertson (HR) effects, have been proposed as causes of these correlates of recombination. Here, we use DNA sequence polymorphism and divergence data from the noncrossing over dot chromosome of Drosophila to discriminate between two of the major forms of HR effects: selective sweeps and background selection. This chromosome shows reduced levels of silent variability and reduced effectiveness of selection. We show that neither model fits the data on variability. We propose that, in large genomic regions with restricted recombination, HR effects among nonsynonymous mutations undermine the effective strength of selection, so that their background selection effects are weakened. This modified model fits the data on variability and also explains why variability in very large nonrecombining genomes is not completely wiped out. We also show that HR effects of this type can produce an individual selection advantage to recombination, as well as greatly reduce the mean fitness of nonrecombining genomes and genomic region

Multilevel work-family interventions: Creating good-quality employment over the life course

Poor-quality jobs have significant costs for individual workers, their families, and the wider community. Drawing mainly on the Australian case, the authors' focus is on the structural challenges to work-life reconciliation and the multiple-level interventions necessary to create quality employment that supports workers to reconcile work and family over the life course. The authors argue that interventions are necessary in three domains: at the macrosocial and economic level, in the regulatory domain, and in the workplace domain. The nature and success of these interventions is also critical to gender equality and to responding to the changing gender and care composition of the workforce across OECD countries

Variation in the intensity of selection on codon bias over time causes contrasting patterns of base composition evolution in Drosophila

Four-fold degenerate coding sites form a major component of the genome, and are often used to make inferences about selection and demography, so that understanding their evolution is important. Despite previous efforts, many questions regarding the causes of base composition changes at these sites in Drosophila remain unanswered. To shed further light on this issue, we obtained a new whole-genome polymorphism dataset from D. simulans. We analysed samples from the putatively ancestral range of D. simulans, as well as an existing polymorphism dataset from an African population of D. melanogaster. By using D. yakuba as an outgroup, we found clear evidence for selection on 4-fold sites along both lineages over a substantial period, with the intensity of selection increasing with GC content. Based on an explicit model of base composition evolution, we suggest that the observed AT-biased substitution pattern in both lineages is probably due to an ancestral reduction in selection intensity, and is unlikely to be the result of an increase in mutational bias towards AT alone. By using two polymorphism-based methods for estimating selection coefficients over different timescales, we show that the selection intensity on codon usage has been rather stable in D. simulans in the recent past, but the long-term estimates in D. melanogaster are much higher than the short-term ones, indicating a continuing decline in selection intensity, to such an extent that the short-term estimates suggest that selection is only active in the most GC-rich parts of the genome. Finally, we provide evidence for complex evolutionary patterns in the putatively neutral short introns, which cannot be explained by the standard GC-biased gene conversion model. These results reveal a dynamic picture of base composition evolution

Evaluation Context Impacts Neuropsychological Performance of OEF/OIF Veterans with Reported Combat-Related Concussion

Although soldiers of Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF) encounter combat-related concussion at an unprecedented rate, relatively few studies have examined how evaluation context, insufficient effort, and concussion history impact neuropsychological performances in the years following injury. The current study explores these issues in a sample of 119 U.S. veterans (OEF/OIF forensic concussion, n = 24; non-OEF/OIF forensic concussion, n = 20; OEF/OIF research concussion, n = 38; OEF/OIF research without concussion, n = 37). The OEF/OIF forensic concussion group exhibited significantly higher rates of insufficient effort relative to the OEF/OIF research concussion group, but a comparable rate of insufficient effort relative to the non-OEF/OIF forensic concussion group. After controlling for effort, the research concussion and the research non-concussion groups demonstrated comparable neuropsychological performance. Results highlight the importance of effort assessment among OEF/OIF and other veterans with concussion history, particularly in forensic contexts

Neuropsychological evaluation of blast-related concussion: Illustrating the challenges and complexities through OEF/OIF case studies

Background/objective: Soldiers of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) sustain blast-related mild traumatic brain injury (concussion) with alarming regularity. This study discusses factors in addition to concussion, such as co-morbid psychological difficulty (e.g. post-traumatic stress) and symptom validity concerns that may complicate neuropsychological evaluation in the late stage of concussive injury. Case report: The study presents the complexities that accompany neuropsychological evaluation of blast concussion through discussion of three case reports of OEF/OIF personnel. Discussion: The authors emphasize uniform assessment of blast concussion, the importance of determining concussion severity according to acute-injury characteristics and elaborate upon non-concussion-related factors that may impact course of cognitive limitation. The authors conclude with a discussion of the need for future research examining the impact of blast concussion (particularly recurrent concussion) and neuropsychological performance

Analytical solution of a generalized Penna model

In 1995 T.J.Penna introduced a simple model of biological aging. A modified Penna model has been demonstrated to exhibit behaviour of real-life systems including catastrophic senescence in salmon and a mortality plateau at advanced ages. We present a general steady-state, analytic solution to the Penna model, able to deal with arbitrary birth and survivability functions. This solution is employed to solve standard variant Penna models studied by simulation. Different Verhulst factors regulating both the birth rate and external death rate are considered.Comment: 6 figure

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

Neuropsychological Outcomes of U.S. Veterans with Report of Remote Blast-Related Concussion and Current Psychopathology

This study explored whether remote blast-related MTBI and/or current Axis I psychopathology contribute to neuropsychological outcomes among OEF/OIF veterans with varied combat histories. OEF/OIF veterans underwent structured interviews to evaluate history of blast-related MTBI and psychopathology and were assigned to MTBI (n = 18), Axis I (n = 24), Co-morbid MTBI/Axis I (n = 34), or post-deployment control (n = 28) groups. A main effect for Axis I diagnosis on overall neuropsychological performance was identified (F(3,100) = 4.81; p = .004), with large effect sizes noted for the Axis I only (d = .98) and Co-morbid MTBI/Axis I (d = .95) groups relative to the control group. The latter groups demonstrated primary limitations on measures of learning/memory and processing speed. The MTBI only group demonstrated performances that were not significantly different from the remaining three groups. These findings suggest that a remote history of blast-related MTBI does not contribute to objective cognitive impairment in the late stage of injury. Impairments, when present, are subtle and most likely attributable to PTSD and other psychological conditions. Implications for clinical neuropsychologists and future research are discussed. (JINS, 2012, 18, 1–11