Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure

Sexual selection protects against extinction

Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorised that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males, and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which depends on mutation load, then sexually selected filtering through ‘genic capture’ could offset the costs of sex because it provides genetic benefits to populations. Here, we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for ~7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress

Family members' experience with in-hospital health care after severe traumatic brain injury : a national multicentre study.

Background Family member’s experience and satisfaction of health care in the acute care and in-patient rehabilitation are important indicators of the quality of health care services provided to patients with severe traumatic brain injury (TBI). The objective was to assess family members’ experience of the health care provided in-hospital to patients with severe TBI, to relate experiences to family member and patient demographics, patients’ function and rehabilitation pathways. Methods Prospective national multicentre study of 122 family members of patients with severe TBI. The family experience of care questionnaire in severe traumatic brain injury (FECQ-TBI) was applied. Independent sample t-tests or analysis of variance (ANOVA) were used to compare the means between 2 or more groups. Paired samples t-tests were used to investigate differences between experience in the acute and rehabilitation phases. Results Best family members` experience were found regarding information during the acute phase, poorest scores were related to discharge. A significantly better care experience was reported in the acute phase compared with the rehabilitation phase (p < 0.05). Worst family members` experience was related to information about consequences of the injury. Patient’s dependency level (p < 0.05) and transferral to non-specialized rehabilitation were related to a worse family members` experience (p < 0.01). Conclusions This study underscores the need of better information to family members of patients with severe TBI in the rehabilitation as well as the discharge phase. The results may be important to improve the services provided to family members and individuals with severe TBI

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

Evolving origin-of-transfer sequences on staphylococcal conjugative and mobilizable plasmids—who’s mimicking whom?

Abstract In Staphylococcus aureus, most multiresistance plasmids lack conjugation or mobilization genes for horizontal transfer. However, most are mobilizable due to carriage of origin-of-transfer (oriT) sequences mimicking those of conjugative plasmids related to pWBG749. pWBG749-family plasmids have diverged to carry five distinct oriT subtypes and non-conjugative plasmids have been identified that contain mimics of each. The relaxasome accessory factor SmpO, encoded by each conjugative plasmid, determines specificity for its cognate oriT. Here we characterized the binding of SmpO proteins to each oriT. SmpO proteins predominantly formed tetramers in solution and bound 5′-GNNNNC-3′ sites within each oriT. Four of the five SmpO proteins specifically bound their cognate oriT. An F7K substitution in pWBG749 SmpO switched oriT-binding specificity in vitro. In vivo, the F7K substitution reduced but did not abolish self-transfer of pWBG749. Notably, the substitution broadened the oriT subtypes that were mobilized. Thus, this substitution represents a potential evolutionary intermediate with promiscuous DNA-binding specificity that could facilitate a switch between oriT specificities. Phylogenetic analysis suggests pWBG749-family plasmids have switched oriT specificity more than once during evolution. We hypothesize the convergent evolution of oriT specificity in distinct branches of the pWBG749-family phylogeny reflects indirect selection pressure to mobilize plasmids carrying non-cognate oriT-mimics.</jats:p

Relationship between epistasis and aggressiveness in resistance of pepper (Capsicum annuum L.) to Phytophthora nicotianae

This study evaluated the types of gene action governing the inheritance of resistance to Phytophthora nicotianae necrosis in populations derived from two crosses involving two susceptible (Beldi and Nabeul II) and one resistant (CM334) cultivars of pepper (Capsicum annuum L.). Populations, composed of Pr, Ps, F1 , F 2 , BC 1 Pr, and BC 1 Ps generations, were inoculated with six P. nicotianae isolates. Generation means analysis indicated that an additive-dominance model was appropriate for P. nicotianae isolates Pn Ko1 , Pn Ko2 and Pn Kr1 , which showed low aggressiveness in the two crosses. For the more aggressive isolates Pn Bz1 , Pn Bz2 and Pn Kr2 , epistasis was an integral component of resistance in the two crosses. The presence of epistasis in the resistance of pepper to P. nicotianae was dependent on the level of aggressiveness of the isolates. Selection in pepper with less aggressive isolates was efficient, but not with more aggressive isolates; on the other hand, selection with more aggressive isolates was more stable. The minimum number of genes controlling resistance was estimated at up to 2.71. In the majority of cases, the additive variance was significant and greater than the environmental and dominance variance

The distribution of genetic diversity in a Brassica oleracea gene bank collection related to the effects on diversity of regeneration, as measured with AFLPs

The ex situ conservation of plant genetic resources in gene banks involves the selection of accessions to be conserved and the maintenance of these accessions for current and future users. Decisions concerning both these issues require knowledge about the distribution of genetic diversity within and between accessions sampled from the gene pool, but also about the changes in variation of these samples as a result of regenerations. These issues were studied in an existing gene bank collection of a cross-pollinating crop using a selection of groups of very similar Dutch white cabbage accessions, and additional groups of reference material representing the Dutch, and the global white cabbage gene pool. Six accessions were sampled both before and after a standard regeneration. 30 plants of each of 50 accessions plus 6 regeneration populations included in the study were characterised with AFLPs, using scores for 103 polymorphic bands. It was shown that the genetic changes as a result of standard gene bank regenerations, as measured by AFLPs, are of a comparable magnitude as the differences between some of the more similar accessions. The observed changes are mainly due to highly significant changes in allele frequencies for a few fragments, whereas for the majority of fragments the alleles occur in similar frequencies before and after regeneration. It is argued that, given the changes of accessions over generations, accessions that display similar levels of differentiation may be combined safely

Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients

BACKGROUND: Though the dysfunction of central dopaminergic system has been proposed, the etiology or pathogenesis of schizophrenia is still uncertain partly due to limited accessibility to dopamine receptor. The purpose of this study was to define whether or not the easily accessible dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia. RESULTS: 44 drug-medicated schizophrenics for more than 3 years, 28 drug-free schizophrenics for more than 3 months, 15 drug-naïve schizophrenic patients, and 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of D3 and D5 dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors was compared in each group. After taking antipsychotics in drug-free and drug-naïve patients, the dopamine receptors of peripheral lymphocytes were sequentially studied 2nd week and 8th week after medication. In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes significantly increased compared to that of controls and drug-medicated schizophrenics, and D5 dopamine receptor mRNA expression increased compared to that of drug-medicated schizophrenics. After taking antipsychotics, mRNA of dopamine receptors peaked at 2(nd) week, after which it decreases but the level was above baseline one at 8(th) week. Drug-free and drug-naïve patients were divided into two groups according to dopamine receptor expression before medications, and the group of patients with increased dopamine receptor expression had more severe psychiatric symptoms. CONCLUSIONS: These results reveal that the molecular biologically-determined dopamine receptors of peripheral lymphocytes are reactive, and that increased expression of dopamine receptor in peripheral lymphocyte has possible clinical significance for subgrouping of schizophrenis

Purging of inbreeding depression within the Irish Holstein-Friesian population

The objective of this study was to investigate whether inbreeding depression in milk production or fertility performance has been partially purged due to selection within the Irish Holstein-Friesian population. Classical, ancestral (i.e., the inbreeding of an individual's ancestors according to two different formulae) and new inbreeding coefficients (i.e., part of the classical inbreeding coefficient that is not accounted for by ancestral inbreeding) were computed for all animals. The effect of each coefficient on 305-day milk, fat and protein yield as well as calving interval, age at first calving and survival to second lactation was investigated. Ancestral inbreeding accounting for all common ancestors in the pedigree had a positive effect on 305-day milk and protein yield, increasing yields by 4.85 kg and 0.12 kg, respectively. However, ancestral inbreeding accounting only for those common ancestors, which contribute to the classical inbreeding coefficient had a negative effect on all milk production traits decreasing 305-day milk, fat and protein yields by -8.85 kg, -0.53 kg and -0.33 kg, respectively. Classical, ancestral and new inbreeding generally had a detrimental effect on fertility and survival traits. From this study, it appears that Irish Holstein-Friesians have purged some of their genetic load for milk production through many years of selection based on production alone, while fertility, which has been less intensely selected for in the population demonstrates no evidence of purging