Nonparametric estimation of natural selection on a quantitative trait using mark-recapture data

Assessing natural selection on a phenotypic trait in wild populations is of primary importance for evolutionary ecologists. To cope with the imperfect detection of individuals inherent to monitoring in the wild, we develop a nonparametric method for evaluating the form of natural selection on a quantitative trait using mark-recapture data. Our approach uses penalized splines to achieve flexibility in exploring the form of natural selection by avoiding the need to specify an a priori parametric function. If needed, it can help in suggesting a new parametric model. We employ Markov chain Monte Carlo sampling in a Bayesian framework to estimate model parameters. We illustrate our approach using data for a wild population of sociable weavers (Philetairus socius) to investigate survival in relation to body mass. In agreement with previous parametric analyses, we found that lighter individuals showed a reduction in survival. However, the survival function was not symmetric, indicating that body mass might not be under stabilizing selection as suggested previously.     

Why join groups? Lessons from parasite‐manipulated Artemia

Grouping behaviours (e.g. schooling, shoaling and swarming) are commonly explicated through adaptive hypotheses such as protection against predation, access to mates or improved foraging. However, the hypothesis that aggregation can result from manipulation by parasites to increase their transmission has never been demonstrated. We investigated this hypothesis using natural populations of two crustacean hosts (Artemia franciscana and Artemia parthenogenetica) infected with one cestode and two microsporidian parasites. We found that swarming propensity increased in cestode‐infected hosts and that red colour intensity was higher in swarming compared with non‐swarming infected hosts. These effects likely result in increased cestode transmission to its final avian host. Furthermore, we found that microsporidian‐infected hosts had both increased swarming propensity and surfacing behaviour. Finally, we demonstrated using experimental infections that these concurrent manipulations result in increased spore transmission to new hosts. Hence, this study suggests that parasites can play a prominent role in host grouping behaviours.     

Male-female coevolution in the wild: evidence from a time series in artemia franciscana

Sexual conflicts are ubiquitous in nature and are expected to lead to an antagonistic coevolution between the sexes. This coevolutionary process is driven by selection on sexually antagonistic traits that can either be directional or fluctuating. In this study, we used dormant cysts of Artemia franciscana, collected in the same population in three different years over a 23-year period (corresponding to ～160 generations in this system), to investigate male-female coevolution in natural conditions over time. We performed a cross experiment study where reproduction of females mated to males from the past, present, or future was monitored until death. In agreement with a model of "fluctuating selection," we found that females survived better and had longer interbrood intervals when mated with their contemporary males compared to when mated with males from the future or the past. However, female weekly and lifetime reproductive successes displayed no differences between contemporary and noncontemporary matings. Finally, the coevolutionary patterns ("arms race dynamics" or "fluctuating selection dynamics") possibly acting on female relative fitness could not be discriminated. This study is the first direct demonstration that the process of male-female coevolution, previously revealed by experimental evolution in laboratory artificial conditions, can occur in nature on a short evolutionary time scale.     

Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling.

The mitogen activated protein (MAP) kinase module: (Raf -->MEK-->ERKs) is central to the control of cell growth, cell differentiation and cell survival. The fidelity of signalling and the spatio-temporal activation are key determinants in generating precise biological responses. The fidelity is ensured by scaffold proteins - protein kinase 'insulators' - and by specific docking sites. The duration and the intensity of the response are in part controlled by the compartmentalization of the signalling molecules. Growth factors promote rapid nuclear translocation and persistent activation of p42/p44 MAP kinases, respectively and ERK2/ERK1, during the entire G1 period with an extinction during the S-phase. These features are exquisitely controlled by the temporal induction of the MAP kinase phosphatases, MKP1-3. MKP1 and 2 induction is strictly controlled by the activation of the MAP kinase module providing evidence for an auto-regulatory mechanism. This negative regulatory loop is further enhanced by the capacity of p42/p44 MAPK to phosphorylate MKP1 and 2. This action reduces the degradation rate of MKPs through the ubiquitin-proteasomal system. Whereas the two upstream kinases of the module (Raf and MEK) remain cytoplasmic, ERKs (anchored to MEK in the cytoplasm of resting cells) rapidly translocate to the nucleus upon mitogenic stimulation. This latter process is rapid, reversible and controlled by the strict activation of the MAPK cascade. Following long-term MAPK stimulation, p42/p44 MAPKs progressively accumulate in the nucleus in an inactive form. Therefore we propose that the nucleus represents a site for ERK action, sequestration and signal termination. With the generation of knockdown mice for each of the ERK isoforms, we will illustrate that besides controlling cell proliferation the ERK cascade also controls cell differentiation and cell behaviour.     

NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues

Chronic inflammation is a hallmark of pulmonary diseases, which leads to lung parenchyma destruction (emphysema) and obstructive bronchiolitis occurring in both chronic obstructive pulmonary disease and asthma. Inflammation is strongly correlated with low intracellular cAMP levels and increase in specific cAMP hydrolyzing activity. The aim of the present study was to investigate the role of the cyclic phosphodiesterase type 4 (PDE4) in human lung and to determine the effects of NCS 613, a new PDE4 inhibitor, on lung inflammation and bronchial hyperresponsiveness. High cAMP-PDE activities were found in the cytosoluble fractions from human lung parenchyma and distal bronchi. PDE4 (rolipram sensitive) represented 40% and 56% of total cAMP-PDE activities in the above-corresponding tissues. Moreover, PDE4A, PDE4B, PDE4C, and PDE4D isoforms were detected in all three subcellular fractions (cytosolic, microsomal, and nuclear) with differential distributions according to specific variants. Pharmacological treatments with NCS 613 significantly decreased PDE4 activity and reduced IκBα degradation in cultured parenchyma, both of which are usually correlated with a lower inflammation status. Moreover, NCS 613 pretreatment potentiated isoproterenol-induced relaxations in human distal bronchi, while reducing TNF-α-induced hyperresponsiveness in cultured bronchi, as assessed in the presence of methacholine, U-46619, or histamine. This reducing effect of NCS 613 on human bronchi hyperresponsiveness triggered by TNF-α was related to a lower expression level of PDE4B and PDE4C, as well as a downregulation of the phosphorylated forms of p38-MAPK, CPI-17, and MYPT-1, which are known to control tone. In conclusion, specific PDE4 inhibitors, such as NCS 613, may represent an alternative and isoform-specific approach toward reducing human lung inflammation and airway overreactivity.     

Testing the emergence of New Caledonia: fig wasp mutualism as a case study and a review of evidence

While geologists suggest that New Caledonian main island (Grande Terre) was submerged until ca 37 Ma, biologists are struck by the presence of supposedly Gondwanan groups on the island. Among these groups are the Oreosycea fig trees (Ficus, Moraceae) and their Dolichoris pollinators (Hymenoptera, Agaonidae). These partners are distributed in the Paleotropics and Australasia, suggesting that their presence on New Caledonia could result from Gondwanan vicariance. To test this hypothesis, we obtained mitochondrial and nuclear markers (5.3 kb) from 28 species of Dolichoris, used all available sequences for Oreosycea, and conducted phylogenetic and dating analyses with several calibration strategies. All our analyses ruled out a vicariance scenario suggesting instead that New Caledonian colonization by Dolichoris and Oreosycea involved dispersal across islands from Sundaland ca 45.9-32.0 Ma. Our results show that successful long-distance dispersal of obligate mutualists may happen further suggesting that presence of intimate mutualisms on isolated islands should not be used as a priori evidence for vicariance. Comparing our results to a review of all the published age estimates for New Caledonian plant and animal taxa, we showed that support for a vicariant origin of the island biota is still lacking. Finally, as demonstrating a causal relationship between geology and biology requires independent evidence, we argue that a priori assumptions about vicariance or dispersal should not be used to constrain chronograms. This circular reasoning could lead to under or overestimation of age estimates.     

The distribution of beneficial and fixed mutation fitness effects close to an optimum

The distribution of the selection coefficients of beneficial mutations is pivotal to the study of the adaptive process, both at the organismal level (theories of adaptation) and at the gene level (molecular evolution). A now famous result of extreme value theory states that this distribution is an exponential, at least when considering a well-adapted wild type. However, this prediction could be inaccurate under selection for an optimum (because fitness effect distributions have a finite right tail in this case). In this article, we derive the distribution of beneficial mutation effects under a general model of stabilizing selection, with arbitrary selective and mutational covariance between a finite set of traits. We assume a well-adapted wild type, thus taking advantage of the robustness of tail behaviors, as in extreme value theory. We show that, under these general conditions, both beneficial mutation effects and fixed effects (mutations escaping drift loss) are beta distributed. In both cases, the parameters have explicit biological meaning and are empirically measurable; their variation through time can also be predicted. We retrieve the classic exponential distribution as a subcase of the beta when there are a moderate to large number of weakly correlated traits under selection. In this case too, we provide an explicit biological interpretation of the parameters of the distribution. We show by simulations that these conclusions are fairly robust to a lower adaptation of the wild type and discuss the relevance of our findings in the context of adaptation theories and experimental evolution.     

Structure of an anti-blood group A Fv and improvement of its binding affinity without loss of specificity.

The specificity of antibody recognition of the ABO blood group trisaccharide antigens has been explored by crystal structure analysis and mutation methods. The crystal structure of the Fv corresponding to the anti-blood group A antibody AC1001 has been determined to 2.2-A resolution and reveals a binding pocket that is complementary to the blood group A-trisaccharide antigen. The effect of mutating specific residues lining this pocket on binding to the A and B blood group oligosaccharide antigens was investigated through a panel of single point mutations and through a phage library of mutations in complementarity determining region H3. Both approaches gave several mutants with improved affinity for antigen. Surface plasmon resonance indicated up to 8-fold enhancement in affinity for the A-pentasaccharide with no observable binding to the blood group B antigen. This is the first example of single point mutations in a carbohydrate-binding antibody resulting in significant increases in binding affinity without loss of specificity.     

Deleterious mutations in a hybrid zone: can mutational load decrease the barrier to gene flow?

The aim of this paper is to investigate the effect of deleterious mutations in a hybrid zone maintained by selection against hybrids. In such zones, linkage disequilibria among hybrid depression loci, resulting from a balance between migration and selection, are crucial in maintaining the barrier because they allow each locus, in addition to its own selection coefficient, to cumulate indirect selective effects from other loci. Deleterious alleles produce heterosis and increase by this means the effective migration rate in structured populations. In a hybrid zone, they therefore contribute to decrease linkage disequilibria as well as the barrier to gene flow imposed by hybrid depression. However, deleterious mutations have no effect: (i) when selection against hybrids is weak, because linkage disequilibria are small even without heterosis in this case, or (ii) when selection against hybrids is so strong that it overwhelms heterosis. On the other hand, with moderate selection against hybrids, the decrease in the strength of the barrier due to heterosis may reach detectable levels, although it requires relatively small population sizes and/or migration rates. The effect is expected to be small and only within small genomes where loci are tightly linked can it become strong. Nevertheless, neglecting mutational load may to some extent obscure the estimations of selective parameters based either on artificial F1 crosses or on cline characteristics.