Consequences of genetic erosion on fitness and phenotypic plasticity in European tree frog populations (Hyla arborea).

The detrimental effects of genetic erosion on small isolated populations are widely recognized contrary to their interactions with environmental changes. The ability of genotypes to plastically respond to variability is probably essential for the persistence of these populations. Genetic erosion impact may be exacerbated if inbreeding affects plastic responses or if their maintenance were at higher phenotypic costs. To understand the interplay 'genetic erosion-fitness-phenotypic plasticity', we experimentally compared, in different environments, the larval performances and plastic responses to predation of European tree frogs (Hyla arborea) from isolated and connected populations. Tadpoles from isolated populations were less performant, but the traits affected were environmental dependant. Heterosis observed in crosses between isolated populations allowed attributing their low fitness to inbreeding. Phenotypic plasticity can be maintained in the face of genetic erosion as inducible defences in response to predator were identical in all populations. However, the higher survival and developmental costs for isolated populations in harsh conditions may lead to an additional fitness loss for isolated populations.

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.

BACKGROUND: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. RESULTS: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. CONCLUSIONS: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

Habitat selection by grey mullets (Osteichthyes: Mugilidae) in Mediterranean estuaries: the role of salinity.

A stratified study of microhabitat use by grey mullet on the island of Minorca (Balearic archipelago, western Mediterranean) showed that the distribution of all the species was dramatically affected by salinity. Sites with a salinity level under 15 were positively selected in spring and summer by those species whose growth performance was the best in oligomesohaline water (Liza ramado and Mugil cephalus) but also by a species whose growth was not affected by salinity (Chelon labrosus). Liza aurata concentrated in polyhaline and euhaline sites, where growth was improved, a pattern also exhibited by Liza saliens. Both species avoided fresh water sites all year round. As a consequence, community structure was correlated with salinity. The above reported electivity patterns often disappeared in autumn, when most grey mullets migrate off-shore.

Phenotypic plasticity in the Caribbean sponge Callyspongia vaginalis (Porifera: Haplosclerida)

Sponge morphological plasticity has been a long-standing source of taxonomic difficulty. In the Caribbean, several morphotypes of the sponge Callyspongia vaginalis have been observed. To determine the taxonomic status of three of these morphotypes and their relationship with the congeneric species C. plicifera and C. fallax, we compared the spicule composition, spongin fiber skeleton and sequenced fragments of the mitochondrial genes 16S and COI and nuclear genes 28S and 18S ribosomal RNA. Phylogenetic analyses with ribosomal markers 18S and 28S rRNA confirmed the position of our sequences within the Callyspongiidae. None of the genetic markers provided evidence for consistent differentiation among the three morphotypes of C. vaginalis and C. fallax, and only C. plicifera stood as a distinct species. The 16S mtDNA gene was the most variable molecular marker for this group, presenting a nucleotide variability (π = 0.024) higher than that reported for COI. Unlike recent studies for other sponge genera, our results indicate that species in the genus Callyspongia maintain a high degree of phenotypic plasticity, and that morphological characteristics may not reflect reproductive boundaries in C. vaginalis.

Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.

Postglacial recolonization at a snail's pace (Trochulus villosus): confronting competing refugia hypotheses using model selection.

The localization of Last Glacial Maximum (LGM) refugia is crucial information to understand a species' history and predict its reaction to future climate changes. However, many phylogeographical studies often lack sampling designs intensive enough to precisely localize these refugia. The hairy land snail Trochulus villosus has a small range centred on Switzerland, which could be intensively covered by sampling 455 individuals from 52 populations. Based on mitochondrial DNA sequences (COI and 16S), we identified two divergent lineages with distinct geographical distributions. Bayesian skyline plots suggested that both lineages expanded at the end of the LGM. To find where the origin populations were located, we applied the principles of ancestral character reconstruction and identified a candidate refugium for each mtDNA lineage: the French Jura and Central Switzerland, both ice-free during the LGM. Additional refugia, however, could not be excluded, as suggested by the microsatellite analysis of a population subset. Modelling the LGM niche of T. villosus, we showed that suitable climatic conditions were expected in the inferred refugia, but potentially also in the nunataks of the alpine ice shield. In a model selection approach, we compared several alternative recolonization scenarios by estimating the Akaike information criterion for their respective maximum-likelihood migration rates. The 'two refugia' scenario received by far the best support given the distribution of genetic diversity in T. villosus populations. Provided that fine-scale sampling designs and various analytical approaches are combined, it is possible to refine our necessary understanding of species responses to environmental changes.

When genetic load does not correlate with phenotypic spectrum: lessons from the GnRH receptor (GNRHR).

CONTEXT: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. OBJECTIVE: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. SUBJECTS: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. RESULTS: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. CONCLUSIONS: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes.

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: relevance to ocular dysgenesis and hearing impairment.

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

Population-based registration of phenotypic anatomic and familial data for melanoma: results from a Swiss multicentric study

CONTEXT AND OBJECTIVES: A multicentric study was set up to assess the feasibility for Swiss cancer registries of actively retrieving 3 additional variables of epidemiological and a etiological relevance for melanoma, and of potential use for the evaluation of prevention campaigns. MATERIAL AND METHODS: The skin type, family history of melanoma and precise anatomical site were retrieved for melanoma cases registered in 5 Swiss cantons (Neuchâtel, St-Gall and Appenzell, Vaud and Wallis) over 3 to 6 consecutive years (1995-2002). Data were obtained via a short questionnaire administered by the physicians - mostly dermatologists - who originally excised the lesions. As the detailed body site was routinely collected in Ticino, data from this Cancer Registry were included in the body site analysis. Relative melanoma density (RMD) was computed by the ratio of observed to expected numbers of melanomas allowing for body site surface areas, and further adjusted for site-specific melanocyte density. RESULTS: Of the 1,645 questionnaires sent, 1,420 (86.3%) were returned. The detailed cutaneous site and skin type were reliably obtained for 84.7% and 78.7% of questionnaires, and family history was known in 76% of instances. Prevalence of sun-sensitive subjects and patients with melanoma affected first-degree relatives, two target groups for early detection and surveillance campaigns were 54.1% and 3.4%, respectively. After translation into the 4th digit of the International Classification of Diseases for Oncology, the anatomical site codes from printed (original information) and pictorial support (body chart from the questionnaire) concurred for 94.6% of lesions. Discrepancies occurred mostly for lesions on the upper, outer part of the shoulder for which the clinician's textual description was "shoulder blade". This differential misclassification suggests under-estimation by about 10% of melanomas of the upper limbs and an over-estimation of 5% for truncal melanomas. Sites of highest melanoma risk were the face, the shoulder and the upper arm for sexes, the back for men and the leg for women. Three major features of this series were: (1) an unexpectedly high RMD for the face in women (6.2 vs 4.2 in men), (2) the absence of a male predominance for melanomas on the ears, and (3) for the upper limbs, a steady gradient of increasing melanoma density with increasing proximity to the trunk, regardless of sex. DISCUSSION AND CONCLUSION: The feasibility of retrieving the skin type, the precise anatomical location and family history of melanoma in a reliable manner was demonstrated thanks to the collaboration of Swiss dermatologists. Use of a schematic body drawing improves the quality of the anatomical site data and facilitate the reporting task of doctors. Age and sex patterns of RMD paralleled general indicators of sun exposure and behaviour, except for the hand (RMD=0.2). These Swiss results support some site or sun exposure specificity in the aetiology of melanoma.

Patterns of positive selection in seven ant genomes.

The evolution of ants is marked by remarkable adaptations that allowed the development of very complex social systems. To identify how ant-specific adaptations are associated with patterns of molecular evolution, we searched for signs of positive selection on amino-acid changes in proteins. We identified 24 functional categories of genes which were enriched for positively selected genes in the ant lineage. We also reanalyzed genome-wide data sets in bees and flies with the same methodology to check whether positive selection was specific to ants or also present in other insects. Notably, genes implicated in immunity were enriched for positively selected genes in the three lineages, ruling out the hypothesis that the evolution of hygienic behaviors in social insects caused a major relaxation of selective pressure on immune genes. Our scan also indicated that genes implicated in neurogenesis and olfaction started to undergo increased positive selection before the evolution of sociality in Hymenoptera. Finally, the comparison between these three lineages allowed us to pinpoint molecular evolution patterns that were specific to the ant lineage. In particular, there was ant-specific recurrent positive selection on genes with mitochondrial functions, suggesting that mitochondrial activity was improved during the evolution of this lineage. This might have been an important step toward the evolution of extreme lifespan that is a hallmark of ants.

Startegy selection during exploratory behavior: sex differences, uncertainty and risk managment

This study deals with the psychological processes underlying the selection of appropriate strategy during exploratory behavior. A new device was used to assess sexual dimorphisms in spatial abilities that do not depend on spatial rotation, map reading or directional vector extraction capacities. Moreover, it makes it possible to investigate exploratory behavior as a specific response to novelty that trades off risk and reward. Risk management under uncertainty was assessed through both spontaneous searching strategies and signal detection capacities. The results of exploratory behavior, detection capacities, and decision-making strategies seem to indicate that women's exploratory behavior is based on risk-reducing behavior while men behavior does not appear to be influenced by this variable. This difference was interpreted as a difference in information processing modifying beliefs concerning the likelihood of uncertain events, and therefore influencing risk evaluation.

Diversity and efficiency of bradyrhizobium strains isolated from soil samples collected from around sesbania virgata roots using cowpea as trap species

The genetic diversity of ten Bradyrhizobium strains was evaluated for tolerance to high temperatures, to different salinity levels and for the efficiency of symbiosis with cowpea plants (Vigna unguiculata (L.) Walp.). Eight of these strains were isolated from nodules that appeared on cowpea after inoculation with suspensions of soil sampled from around the root system of Sesbania virgata (wand riverhemp) in ecosystems of South Minas Gerais. The other two strains used in our analyses as references, were from the Amazon and are currently recommended as cowpea inoculants. Genetic diversity was analyzed by amplifying repetitive DNA elements with the BOX primer, revealing high genetic diversity with each strain presenting a unique band profile. Leonard jar assays showed that the strains UFLA 03-30 and UFLA 03-38 had the highest N2-fixing potentials in symbiosis with cowpea. These strains had more shoot and nodule dry matter, more shoot N accumulation, and a higher relative efficiency than the strains recommended as inoculants. All strains grew in media of pH levels ranging from 4.0 to 9.0. The strains with the highest N2-fixing efficiencies in symbiosis with cowpea were also tolerant to the greatest number of antibiotics. However, these strains also had the lowest tolerance to high salt concentrations. All strains, with the exceptions of UFLA 03-84 and UFLA 03-37, tolerated temperatures of up to 40 ºC. The genetic and phenotypic characteristics of the eight strains isolated from soils of the same region were highly variable, as well as their symbiotic efficiencies, despite their common origin. This variability highlights the importance of including these tests in the selection of cowpea inoculant strains.