Retroviral Integration Site Selection

The stable insertion of a copy of their genome into the host cell genome is an essential step of the life cycle of retroviruses. The site of viral DNA integration, mediated by the viral-encoded integrase enzyme, has important consequences for both the virus and the host cell. The analysis of retroviral integration site distribution was facilitated by the availability of the human genome sequence, revealing the non-random feature of integration site selection and identifying different favored and disfavored genomic locations for individual retroviruses. This review will summarize the current knowledge about retroviral differences in their integration site preferences as well as the mechanisms involved in this process.

Emergence of young human genes after a burst of retroposition in primates.

The origin of new genes through gene duplication is fundamental to the evolution of lineage- or species-specific phenotypic traits. In this report, we estimate the number of functional retrogenes on the lineage leading to humans generated by the high rate of retroposition (retroduplication) in primates. Extensive comparative sequencing and expression studies coupled with evolutionary analyses and simulations suggest that a significant proportion of recent retrocopies represent bona fide human genes. We estimate that at least one new retrogene per million years emerged on the human lineage during the past approximately 63 million years of primate evolution. Detailed analysis of a subset of the data shows that the majority of retrogenes are specifically expressed in testis, whereas their parental genes show broad expression patterns. Consistently, most retrogenes evolved functional roles in spermatogenesis. Proteins encoded by X chromosome-derived retrogenes were strongly preserved by purifying selection following the duplication event, supporting the view that they may act as functional autosomal substitutes during X-inactivation of late spermatogenesis genes. Also, some retrogenes acquired a new or more adapted function driven by positive selection. We conclude that retroduplication significantly contributed to the formation of recent human genes and that most new retrogenes were progressively recruited during primate evolution by natural and/or sexual selection to enhance male germline function.

Dominant nestlings displaying female-like melanin coloration behave altruistically in the barn owl

When competing over parental resources, young animals may be typically selfish to the point of siblicide. This suggests that limited parental resources promote the evolution of sibling competition rather than altruistic or cooperative behaviours. In striking contrast, we show here that in 71% of experimental three-chick broods, nestling barn owls, Tyto alba, gave food to their siblings on average twice per night. This behaviour prevailed in the first-born dominant nestlings rather than the last-born subordinate nestlings. It was also more prevalent in individuals displaying a heritable dark phaeomelanin-based coloration, a typical female-specific plumage trait (owls vary from dark reddish to white, females being on average darker reddish than males). Stealing food items from siblings, which occurred in 81% of the nests, was more frequent in light than dark phaeomelanic dominant nestlings. We suggest that food sharing has evolved in the barn owl because parents store prey items in their nest that can be used by the offspring to feed their nestmates to derive indirect (kin selection) or direct benefits (pseudoreciprocity or by-product mutualism). The cost of feeding siblings may be relatively low for dominant individuals while the indirect genetic benefits could be high given that extrapair paternity is infrequent in this species. Thus, in situations in which young animals have access to more food resources than they currently need, they can altruistically share them with their siblings.

Maternal and paternal contributions to pathogen resistance dependent on development stage in a whitefish (Salmonidae)

It is often assumed that maternal and paternal contributions to offspring phenotype change over the lifetime of an individual. However, studies on parental effects typically suffer from the problems that heritabilities and maternal environmental effects are difficult to separate, and that both may depend on environmental factors and developmental stage. In order to experimentally disentangle maternal from paternal contributions and the likely effects of developmental stage from ecological effects, we sampled a natural population of the whitefish Coregonus palaea, used gametes for full-factorial in vitro fertilizations, raised over 10000 of the resulting offspring singly at controlled conditions, and exposed them at different points during embryonic development to one of two strains of Pseudomonas fluorescens that differed in their virulence characteristics (only one caused mortality, while both delayed hatching and reduced growth). Vulnerability to infection increased markedly over embryo development. This change coincided with a distinct shift in the importance of maternal to additive genetic effects on survival. Timing of exposure also affected the variance components for hatching time and larval length, but in a less consistent direction than the variance components for mortality. No significant genetic variation was found for any reaction norms across time points of exposure, indicating a uniformity among genotypes in how susceptibility changed over development. Phenotypes were also typically correlated across time points, which could constrain the evolution of the reaction norms. Our experiment demonstrates that the relative maternal and paternal contributions to susceptibility to an infection, and hence the evolutionary potential to respond to pathogen-induced selection, depends not only on the kind of pathogenic stress but also on the timing of the challenge.

Associations between parental and child attachment representations.

In the present article on intergenerational transmission of attachment representations, we use mothers' and fathers' Adult Attachment Interview classifications to predict a 3-year-old's responses to the Attachment Story Completion Task (ASCT). We present a Q-sort coding procedure for the ASCT, which was developed for children as young as three. The Q-sort yields scores on four attachment dimensions (security, deactivation, hyperactivation, and disorganization). One-way ANOVAs revealed significant mother-child associations for each dimension, although results for the hyperactivation and disorganization dimensions were significant only according to contrast tests. Conversely, no father-child association was found, regardless of the dimension considered. Findings are discussed in terms of the respective part played by each parent in their children's emotional development.

Do pseudo-absence selection strategies influence species distribution models and their predictions? An information-theoretic approach based on simulated data

Background Multiple logistic regression is precluded from many practical applications in ecology that aim to predict the geographic distributions of species because it requires absence data, which are rarely available or are unreliable. In order to use multiple logistic regression, many studies have simulated "pseudo-absences" through a number of strategies, but it is unknown how the choice of strategy influences models and their geographic predictions of species. In this paper we evaluate the effect of several prevailing pseudo-absence strategies on the predictions of the geographic distribution of a virtual species whose "true" distribution and relationship to three environmental predictors was predefined. We evaluated the effect of using a) real absences b) pseudo-absences selected randomly from the background and c) two-step approaches: pseudo-absences selected from low suitability areas predicted by either Ecological Niche Factor Analysis: (ENFA) or BIOCLIM. We compared how the choice of pseudo-absence strategy affected model fit, predictive power, and information-theoretic model selection results. Results Models built with true absences had the best predictive power, best discriminatory power, and the "true" model (the one that contained the correct predictors) was supported by the data according to AIC, as expected. Models based on random pseudo-absences had among the lowest fit, but yielded the second highest AUC value (0.97), and the "true" model was also supported by the data. Models based on two-step approaches had intermediate fit, the lowest predictive power, and the "true" model was not supported by the data. Conclusion If ecologists wish to build parsimonious GLM models that will allow them to make robust predictions, a reasonable approach is to use a large number of randomly selected pseudo-absences, and perform model selection based on an information theoretic approach. However, the resulting models can be expected to have limited fit.

Video-assisted thoracoscopic surgery lobectomy or open lobectomy for non-small-cell lung cancer? Minimizing selection bias in observational studies.

PURPOSE OF REVIEW: Adherence to preventive measures and prescribed medications is the cornerstone of the successful management of hypertension. The role of adherence is particularly important when treatments are not providing the expected clinical results, for example, in patients with resistant hypertension. The goal of this article is to review the recent observations regarding drug adherence in resistant hypertension. RECENT FINDINGS: Today, the role of drug adherence as a potential cause of resistant hypertension is largely underestimated. Most studies suggest that a low adherence to the prescribed medications can affect up to 50% of patients with resistant hypertension.A good adherence to therapy is generally associated with an improved prognosis. Nonetheless, adherence should probably not be a target for treatment per se because data on adherence should always be interpreted in the view of clinical results. In our opinion, the availability of reliable data on drug adherence would be a major help for physicians to manage patients apparently resistant to therapy. SUMMARY: The actual development of new drugs for hypertension is slow. Thus, focusing on drug adherence to the drugs available is an important way to improve blood pressure control in the population. More emphasis should be put on measuring drug adherence in patients with resistant hypertension to avoid costly investigations and treatments.

Polymorphism at a sex-linked transcription cofactor in European tree frogs (Hyla arborea): Sex-antagonistic selection or neutral processes?

Nascent sex chromosomes offer a unique opportunity to investigate the evolutionary fate of genesrecently trapped in non-recombining segments. A housekeeping gene (MED15) was recently shown to lie on the nascent sex-chromosomes of the European tree frog (Hyla arborea), with different alleles fixed on the X and the Y chromosomes. Here we document a polymorphism (glutamine deletion) in the X copy of the gene, and use population surveys and experimental crosses to test whether this polymorphism is neutral or maintained by sex-antagonistic selection. Tadpoles from parents of known genotypes revealed significant discrepancies from Mendelian inheritance, suggesting possible sex-antagonistic effects under laboratory conditions. Quantitatively, however, these effects did not meet the conditions for polymorphism maintenance. Furthermore, field estimates of female genotypic frequencies did not differ from Hardy-Weinberg equilibrium and allelic frequencies on the X chromosome did not differ between sexes. In conclusion, although sex antagonistic effects cannot be excluded given the laboratory conditions, the X-linked polymorphism under study appears neutral in the wild. Alternatively, sex-antagonistic selection might still account for the fixation of a male specific allele on the Y chromosome.

Extensive variation at MHC DRB in the New Zealand sea lion (Phocarctos hookeri) provides evidence for balancing selection.

Marine mammals are often reported to possess reduced variation of major histocompatibility complex (MHC) genes compared with their terrestrial counterparts. We evaluated diversity at two MHC class II B genes, DQB and DRB, in the New Zealand sea lion (Phocarctos hookeri, NZSL) a species that has suffered high mortality owing to bacterial epizootics, using Sanger sequencing and haplotype reconstruction, together with next-generation sequencing. Despite this species' prolonged history of small population size and highly restricted distribution, we demonstrate extensive diversity at MHC DRB with 26 alleles, whereas MHC DQB is dimorphic. We identify four DRB codons, predicted to be involved in antigen binding, that are evolving under adaptive evolution. Our data suggest diversity at DRB may be maintained by balancing selection, consistent with the role of this locus as an antigen-binding region and the species' recent history of mass mortality during a series of bacterial epizootics. Phylogenetic analyses of DQB and DRB sequences from pinnipeds and other carnivores revealed significant allelic diversity, but little phylogenetic depth or structure among pinniped alleles; thus, we could neither confirm nor refute the possibility of trans-species polymorphism in this group. The phylogenetic pattern observed however, suggests some significant evolutionary constraint on these loci in the recent past, with the pattern consistent with that expected following an epizootic event. These data may help further elucidate some of the genetic factors underlying the unusually high susceptibility to bacterial infection of the threatened NZSL, and help us to better understand the extent and pattern of MHC diversity in pinnipeds.

Adverse selection, moral hazard, and outlier payment policy

In this article, we analyze the rationale for introducing outlier payments into a prospective payment system for hospitals under adverse selection and moral hazard. The payer has only two instruments: a fixed price for patients whose treatment cost is below a threshold and a cost-sharing rule for outlier patients. We show that a fixed-price policy is optimal when the hospital is sufficiently benevolent. When the hospital is weakly benevolent, a mixed policy solving a trade-off between rent extraction, efficiency, and dumping deterrence must be preferred. We show how the optimal combination of fixed price and partially cost-based payment depends on the degree of benevolence of the hospital, the social cost of public funds, and the distribution of patients severity. [Authors]

Smoking offsets the metabolic benefits of parental longevity in women : the CoLaus study

Rapport de synthèse : Objectif: nous avons regardé si les sujets dont les parents vivaient plus longtemps présentaient des niveaux plus faibles de facteurs de risques cardiovasculaires, y compris pour le syndrome métabolique. Méthodes: nous avons analysé les données d'un échantillon représentatif de la population suisse (1163 hommes et 1398 femmes) âgé de 55 à 75 ans, de la ville de Lausanne. Les participants ont été stratifiés par nombre de parents (0, 1, 2) qui ont vécu jusqu'à 85 ans ou plus. Les associations entre la longévité parentale et les facteurs de risques cardiovasculaires ou les variables métaboliques associées ont été analysées au moyen de régressions linéaires multiples. Résultats: la prévalence ajustée pour l'âge du syndrome métabolique varie de 24.8%, 20.5% à 13.8% chez les femmes (P<0.05) et de 28.8%, 32.1 % à 27.6% chez les hommes (non significatif) pour 0, 1 et 2 parents à forte longévité. L'association entre la longévité parentale et la prévalence du syndrome métabolique est particulièrement forte pour les femmes qui n'ont jamais fumé. Dans ce groupe, les femmes qui ont 2 parents à forte longévité ont un BMI plus faible et un tour de taille moins grand. Chez les gens qui n'ont jamais fumé, pour les deux sexes, les niveaux moyens (95% d'intervalle de confiance) et ajustés de cholestéro-HDL étaient de 1.64(1.61-1.67), 1.67(1.65-1.70) et 1.71(1.65-1.76) mmol/L pour 0, 1 et 2 parents à forte longévité (P<0.01), respectivement. La tendance n'était pas significative chez les anciens fiuneurs et fumeurs actuels. Conclusions: la longévité parentale est associée à un meilleur profil métabolique chez les femmes, mais pas chez les hommes. Les avantages métaboliques du fait d'avoir des parents âgés sont fortement atténués par le tabagisme.

Nestling detectability affects parental feeding preferences in a cavity-nesting bird

In many avian species, nestlings have evolved striking plumage, behaviours and mouth colours to obtain a greater share of parental investment. Studies revealing parental feeding preferences for nestlings with red gapes have proposed that red mouth colour in songbirds can act as a signal of nestling need or condition. Alternative hypotheses suggest that bright nestling mouths in cavity-nesting birds evolved to increase nestling detectability by the parents. We tested whether nestling mouth colour affects parental feeding preferences in great tits, Pants major L. In broods of six young, we experimentally painted mouth gapes and flanges either red or yellow and tested the effect of mouth colour on nestlings' mass gain under two lighting conditions. In nests with high luminosity, there was no significant effect of mouth colour on mass gain. In nests with low luminosity, nestlings with red gapes and flanges gained less mass than nestlings with red gapes and yellow flanges or both yellow gapes and flanges. Our results suggest that, in nests with low luminosity, red mouths decreased nestling detectability to the feeding parents and support the hypothesis that poor luminosity in nesting cavities can select for pale mouths. Overall, our results do not support the hypothesis that red mouth colour signals nestling need or condition to parent great tits.

Perturbation expansions of multilocus fixation probabilities for frequency-dependent selection with applications to the Hill-Robertson effect and to the joint evolution of helping and punishment.

Natural populations are of finite size and organisms carry multilocus genotypes. There are, nevertheless, few results on multilocus models when both random genetic drift and natural selection affect the evolutionary dynamics. In this paper we describe a formalism to calculate systematic perturbation expansions of moments of allelic states around neutrality in populations of constant size. This allows us to evaluate multilocus fixation probabilities (long-term limits of the moments) under arbitrary strength of selection and gene action. We show that such fixation probabilities can be expressed in terms of selection coefficients weighted by mean first passages times of ancestral gene lineages within a single ancestor. These passage times extend the coalescence times that weight selection coefficients in one-locus perturbation formulas for fixation probabilities. We then apply these results to investigate the Hill-Robertson effect and the coevolution of helping and punishment. Finally, we discuss limitations and strengths of the perturbation approach. In particular, it provides accurate approximations for fixation probabilities for weak selection regimes only (Ns < or = 1), but it provides generally good prediction for the direction of selection under frequency-dependent selection.

Strong reproductive barriers in a narrow hybrid zone of West-Mediterranean green toads (Bufo viridis subgroup) with Plio-Pleistocene divergence

Background One key question in evolutionary biology deals with the mode and rate at which reproductive isolation accumulates during allopatric speciation. Little is known about secondary contacts of recently diverged anuran species. Here we conduct a multi-locus field study to investigate a contact zone between two lineages of green toads with an estimated divergence time of 2.7 My, and report results from preliminary experimental crosses. Results The Sicilian endemic Bufo siculus and the Italian mainland-origin B. balearicus form a narrow hybrid zone east of Mt. Etna. Despite bidirectional mtDNA introgression over a ca. 40 km North-South cline, no F1 hybrids could be found, and nuclear genomes display almost no admixture. Populations from each side of the contact zone showed depressed genetic diversity and very strong differentiation (FST = 0.52). Preliminary experimental crosses point to a slightly reduced fitness in F1 hybrids, a strong hybrid breakdown in backcrossed offspring (F1 x parental, with very few reaching metamorphosis) and a complete and early mortality in F2 (F1 x F1). Conclusion Genetic patterns at the contact zone are molded by drift and selection. Local effective sizes are reduced by the geography and history of the contact zone, B. balearicus populations being at the front wave of a recent expansion (late Pleistocene). Selection against hybrids likely results from intrinsic genomic causes (disruption of coadapted sets of genes in backcrosses and F2-hybrids), possibly reinforced by local adaptation (the ranges of the two taxa roughly coincide with the borders of semiarid and arid climates). The absence of F1 in the field might be due to premating isolation mechanisms. Our results, show that these lineages have evolved almost complete reproductive isolation after some 2.7 My of divergence, contrasting sharply with evidence from laboratory experiments that some anuran species may still produce viable F1 offspring after > 20 My of divergence.

Selection on a eumelanic ornament is stronger in the tropics than in temperate zones in the worldwide-distributed barn owl.

Spatial variation in the pattern of natural selection can promote local adaptation and genetic differentiation between populations. Because heritable melanin-based ornaments can signal resistance to environmentally mediated elevation in glucocorticoids, to oxidative stress and parasites, populations may vary in the mean degree of melanic coloration if selection on these phenotypic aspects varies geographically. Within a population of Swiss barn owls (Tyto alba), the size of eumelanic spots is positively associated with survival, immunity and resistance to stress, but it is yet unknown whether Tyto species that face stressful environments evolved towards a darker eumelanic plumage. Because selection regimes vary along environmental gradients, we examined whether melanin-based traits vary clinally and are expressed to a larger extent in the tropics where parasites are more abundant than in temperate zones. To this end, we considered 39 barn owl species distributed worldwide. Barn owl species living in the tropics displayed larger eumelanic spots than those found in temperate zones. This was, however, verified in the northern hemisphere only. Parasites being particularly abundant in the tropics, they may promote the evolution of darker eumelanic ornaments.