Evolution of intraspecific variation : a comparative phylogenetic approach

Understanding the evolution of intraspecific variance is a major research question in evolutionary biology. While its importance to processes operating at individual and population levels is well-documented, much less is known about its role in macroevolutionary patterns. Nevertheless, both experimental and theoretical evidence suggest that the intraspecific variance is susceptible to selection, can transform into interspecific variation and, therefore, is crucial for macroevolutionary processes. The main objectives of this thesis were: (l) to investigate which factors impact evolution of intraspecific variation in Polygonaceae and determine if evolution of intraspecific variation influences species diversification; and (2) to develop a novel comparative phylogenetic method to model evolution of intraspecific variation. Using the buckwheat family, Polygonaceae, as a study system, I demonstrated which life-history and ecological traits are relevant to the evolution of intraspecific variation. I analyzed how differential intraspecific variation drives species diversification patterns. I showed with computer simulations the shortcomings of existing comparative methods with respect to intraspecific variation. I developed a novel comparative model that readily incorporates the intraspecific variance into phylogenetic comparative methods. The obtained results are complimentary, because they affect both empirical and methodological aspects of comparative analysis. Overall, I highlight that intraspecific variation is an important contributor to the macroevolutionary patterns and it should be explicitly considered in the comparative phylogenetic analysis. - En biologie évolutive comprendre l'évolution de la variance intraspécifique est un axe de recherche majeur. Bien que l'importance de cette variation soit bien documentée au niveau individuel et populationnel, on en sait beaucoup moins sur son rôle au niveau macroévolutif. Néanmoins, des preuves expérimentales et théoriques suggèrent que la variance intraspécifique est sensible à la sélection et peut se transformer en variation interspécifique. Par conséquent, elle est cruciale pour mieux comprendre les processus macroévolutifs. Les principaux objectifs de ma thèse étaient : (i) d'enquêter sur les facteurs qui affectent l'évolution de la variation intraspécifique chez les Polygonaceae et de déterminer si l'évolution de cette dernière influence la diversification des espèces, et (2) de développer une nouvelle méthode comparative permettant de modéliser l'évolution de la variation intraspécifique dans un cadre phylogénétique. En utilisant comme système d'étude la famille du sarrasin, les Polygonacées, je démontre que les traits d'histoire de vie sont pertinents pour comprendre l'évolution de la variation intraspécifique. J'ai également analysé l'influence de la variation intraspécifique au niveau de la diversification des espèces. J'ai ensuite démontré avec des données simulées les limites des méthodes comparatives existantes vis à vis de la variation intraspécifique. Finalement, j'ai développé un modèle comparatif qui intègre facilement la variance intraspécifique dans les méthodes comparatives phylogénétiques existantes. Les résultats obtenus lors de ma thèse sont complémentaires car ils abordent aspects empiriques et méthodologiques de l'analyse comparative. En conclusion, je souligne que la variation intraspécifique est un facteur important en macroévolution et qu'elle doit être explicitement considérée lors d'analyses comparatives phylogénétiques.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Détermination de la séquence chronologique entre les impressions électrophotographiques (imprimantes laser et photocopieurs) et les traits de stylos à bille, sans croisement

Ce travail décrit une méthode optique pour établir l'ordre chronologique de la séquence entre les impressions électrophotographiques (imprimantes laser et photocopieurs) et les signatures apposées au stylo à bille, sans croisement. Les auteurs ont utilisé un microscope optique avec des grossissements allant de 100 à 500 fois qui permettent de distinguer l'apparence des microparticules de toner selon qu'elles se situent au-dessus ou au-dessous de l'encre de stylo à billes. Les tests à l'aveugle ont montré un taux de réussite de 100 % permettant ainsi de valider les résultats proposés par Aginsky (2002).

Predictors of leadership: The usual suspects and the suspect traits

In this chapter, I review literature on traits (i.e., individual differences) and their links to leader outcomes. I present an integrated model, the ascription-actuality trait theory, to explain two routes to leader outcomes that stem from traits: the route that objectively matters and the route that appears to matter but objectively may not. I discuss the history of trait research and provide criteria by which we should judge the validity of trait models. Finally, I review trait models that are the most predictive of leadership outcomes and identify those that are non-starters.

Fitness and the level of homozygosity in a social insect.

To date very few studies have addressed the effects of inbreeding in social Hymenoptera, perhaps because the costs of inbreeding are generally considered marginal owing to male haploidy whereby recessive deleterious alleles are strongly exposed to selection in males. Here, we present one of the first studies on the effects of queen and worker homozygosity on colony performance. In a wild population of the ant Formica exsecta, the relative investment of single-queen colonies in sexual production decreased with increased worker homozygosity. This may either stem from increased homozygosity decreasing the likelihood of diploid brood to develop into queens or a lower efficiency of more homozygous workers at feeding larvae and thus a lower proportion of the female brood developing into queens. There was also a significant negative association between colony age and the level of queen but not worker homozygosity. This association may stem from inbreeding affecting queen lifespan and/or their fecundity, and thus colony survival. However, there was no association between queen homozygosity and colony size, suggesting that inbreeding affects colony survival as a result of inbred queens having a shorter lifespan rather than a lower fecundity. Finally, there was no significant association between either worker or queen homozygosity and the probability of successful colony founding, colony size and colony productivity, the three other traits studied. Overall, these results indicate that inbreeding depression may have important effects on colony fitness by affecting both the parental (queen) and offspring (worker)generations cohabiting within an ant colony.

Personality traits, cognition and volumetric MRI changes in elderly patients with early-onset depression: A 2-year follow-up study.

Previous studies revealed personality changes in elderly patients with early-onset depression (EOD) that persist in euthymic stages. However, depression in older patients is a complex disorder that may affect not only personality, but also cognition and brain structure. To address this issue, a cross-sectional comparison and 2-year follow-up of 28 EOD elderly patients and 48 healthy controls included detailed neurocognitive assessment, estimates of brain volumes in limbic areas and white matter hyperintensities, as well as evaluation of the Five Factor Model of personality, in a remitted mood state. Results revealed that cognitive performances as well as brain volumes were preserved in EOD patients both at baseline and at follow-up. The increased Neuroticism factor and Anxiety facet scores as well as the decreased Warmth and Positive Emotions facet scores found at baseline reached the level of healthy controls after 2years. Only the Depression facet scores remained significantly higher in EOD patients compared to controls upon follow-up. Results were independent of depressive relapse since baseline (25% of patients). These findings suggest that both cognitive performances and brain volumes show long-term preservation in older EOD patients. In contrast, the depression-related personality facet might be a trait like marker that persists in the long-term evolution of this disorder.

Biology and pathogenicity of "Waddlia chondrophila"

Abstract This thesis investigates the pathogenicity of a Chlamydia-related bacterium: Waddlia chondrophila, which is suspected to cause abortion in bovines as well as miscarriages in humans. Macrophages represent the first line of defense of the innate immunity against invading pathogens, we thus studied the interaction between W. chondrophila and human macrophages. We observed that W. chondrophila multiplied very efficiently inside monocyte-derived macrophages. Diagnostic tools to detect obligate intracellular bacteria are lacking so we developed a Waddlia specific real-time PCR based on the 16S rRNA encoding gene. Since W. chondrophila could be involved in human miscarriage, we analyzed samples from women having miscarriage or uneventful pregnancy. Waddlia serologies results confirmed an association between the presence of W. chondrophila antibodies and miscarriage (23.2% versus 14.6% in the control group, p-value 0.044). As W. chondrophila's pathogenicity was suggested, we studied its antibiotic susceptibility. W. chondrophila revealed to be susceptible to macrolides and tetracylines but resistant to beta-lactams and fluoroquinolones. This resistance to fluoroquinolones could be explained by mutations in the quinolone resistance determining region of the gyrase (GyrA) and topoisomerase IV (ParC) encoding genes. In conclusion, this thesis allowed to precise the role of W. chondrophila in human miscarriage. However, more studies will be necessary to fully understand the pathogenesis of W. chondrophila in adverse pregnancy outcomes. Résumé Le but de cette thèse a été d'étudier la pathogénicité d'une bactérie apparentée aux Chlamydia: Waddlia chondrophila. Les macrophages représentant la première ligne de défense du système immunitaire inné contre les pathogènes, nous avons d'abord étudié l'interaction entre W. chondrophila and les macrophages humains. Nous avons pu observer que W. chondrophila résistait aux effecteurs microbicides des macrophages et se multipliait efficacement au sein de ces cellules. Au vu du manque d'outils diagnostiques pour détecter cette bactérie intracellulaire obligatoire, nous avons également développé une PCR en temps réel, spécifique pour Waddlia, basée sur le gène de l'ARN ribosomal 16S. Cette PCR a été utilisée dans les différents projets afin de détecter la présence de W. chondrophila. W. chondrophila étant suspectée de pouvoir causer des fausses couches chez la femme, nous avons analysé des échantillons provenant de femmes ayant souffert de fausse couche, ainsi que, comme contrôles, des femmes ayant eu une grossesse normale. Les sérologies ont révélé une association entre la présence d'anticorps dirigés contre Waddlia et la fausse couche (23.2% versus 14.6% chez les contrôles, p-value=0.044). La présence de la bactérie a aussi été détectée par PCR et immunohistochimie dans plusieurs échantillons. L'implication de W. chondrophila dans la fausse couche se précisant, nous avons étudié sa susceptibilité aux antibiotiques. W. chondrophila s'est révélée sensible aux macrolides et aux tetracyclines mais résistante aux beta-lactames et aux quinolones. Cette résistance aux quinolones peut être expliquée par la présence de mutations dans le QRDR (région déterminant la résistance aux quinolones) des gènes gyrA et parC. En conclusion, cette thèse a permis de préciser l'implication de W. chondrophila dans la fausse couche. Des études complémentaires seront cependant nécessaires pour confirmer et préciser le rôle exact de W. chondrophila dans les problèmes obstétricaux.

Study of a sialyltransferase ST3GAL6, in adipogenesis and obesity

RésuméL'obésité et les maladies métaboliques qui lui sont associées tels que le diabète ou les maladies cardiovasculaires ont un impact épidémiologique croissant. Ainsi, les mécanismes moléculaires se produisant dans le tissu adipeux en expansion font l'objet de nombreuses investigations. Dans ce contexte, nous nous sommes particulièrement intéressés à l'adipogénèse, le procédé permettant la formation d'adipocytes matures et fonctionnels. Le gène St3gal6 code pour une enzyme appelée β-galactosidase a2,3-sialyltransferase 6 et participant à la voie de glycosylation. Cette protéine appartient à la famille des a2,3- sialyltransferases dont la fonction principale est de transférer un acide sialique à l'extrémité de chaînes glycosidiques présentes sur les glycoprotéines et les glycolipides. Dans une précédente étude de transcriptomique réalisée chez la souris, St3gal6 a été décrit comme un gène dont l'expression est augmentée dans le tissu adipeux blanc d'animaux en surpoids et dont l'expression est normalisée après une perte de poids. Afin d'étudier le rôle potentiel de St3gal6 dans le développement du tissu adipeux, nous nous sommes intéressés à la régulation de son expression en cas d'obésité ainsi qu'à ses effets sur l'adipogénèse. Nous avons d'abord montré que St3gal6 s'exprime aussi bien dans le tissu adipeux blanc que dans le tissu adipeux brun. Puis nous avons confirmé dans deux différents modèles animaux que l'expression de St3gal6 dans le tissu adipeux était augmentée en cas d'obésité. Nous avons aussi observé in vitro une induction de St3gal6 dans des adipocytes traités par des cytokines pro-inflammatoires sécrétées dans le tissu adipeux d'individus obèses. Enfin, parmi les six membres que compte la famille des a2,3-sialyltransferases, St3gal6 est celui dont l'expression est la plus significativement induite en situation d'obésité. En outre, au cours de la différenciation des adipocytes blancs et bruns, l'expression de St3gal6 est augmentée et son inhibition réduit le potentiel de maturation des adipocytes qui accumulent moins de lipides. A l'inverse, la surexpression de St3gal6 dans des préadipocytes blancs augmente leur taux de différenciation in vitro; la formation de gouttelettes lipidiques et l'expression de genes spécifiques de l'adipocyte mature sont accrues. Enfin, le traitement d'adipocytes blancs in vitro avec un inhibiteur pharmacologique des a2,3-sialyltransferases ou une sialidase clivant les résidus sialylés montre qu'un défaut de a2,3-sialylation affectant les adipocytes diminue leur potentiel adipogénique. Par conséquent, ces résultats suggèrent que St3gal6 est impliqué dans la voie de différenciation des adipocytes et que cette a2,3-sialylation joue un rôle dans le remodelage du tissu adipeux induit par l'obésité.AbstractIn order to better understand molecular events occurring in obesity and leading to its associated complications, we were interested in the biology of adipose tissue and particularly in the study of adipogenesis, the process by which new mature adipocytes develop and accumulate lipids.The β-galactosidase a2,3-sialyltransferase 6 (St3gal6) gene encodes for an enzyme involved in post-translational protein glycosylation. Thereby, St3gal6 enzyme belongs to the a2,3sialyltransferase family whose function is to add sialic acids at outer position on glycosidic chain of glycoproteins or glycolipids. Previously, in mouse, St3gal6 has been described as a gene whose expression in white adipose tissue is increased in overweighted animals and normalized after weight loss. Therefore, we have assumed that St3gal6 may play a role in adipose tissue development and in tissue remodelling triggered by obesity. First we show that St3gal6 is expressed in white but also in brown adipose tissue. St3gal6 upregulation upon weight gain was confirmed in two mouse models of obesity namely diet- induced and genetically-induced obesity. We also report that St3gal6 is induced by pro¬inflammatory cytokines known to be oversecreted in adipose tissue during obesity. Furthermore, St3gal6 is the a2,3-sialyltransferase whose expression is more markedly induced in adipose tissue. In addition, we demonstrate that St3gl6 expression is progressively increased in late stages of white and brown adipogenesis while St3gal6 knockdown inhibits adipocyte differentiation in vitro. Conversely, St3gal6 overexpression in a white preadipocyte cell line increases lipid accumulation during differentiation process and enhances gene expression of mature white adipocyte markers. Finally, using an a2-3 sialyltransferase inhibitor and a sialidase treatment on white adipocyte cell line, we observe that a decreased a2,3-sialylation impairs adipocyte differentiation in vitro. Altogether, these result suggest that St3gal6 plays a role in adipogenesis and in tissue remodelling associated with obesity likely through its enzymatic activity of a2,3-sialylation. Thus, a2,3-sialylation appears as a novel pathway of interest whose precise molecular mechanisms remain to be elucidated in the context of adipose tissue development and adipocyte functions.

The role of climatic tolerances and seed traits in reduced extinction rates of temperate polygonaceae.

The latitudinal diversity gradient (LDG) is one of the most striking and consistent biodiversity patterns across taxonomic groups. We investigate the species richness gradient in the buckwheat family, Polygonaceae, which exhibits a reverse LDG and is, thus, decoupled from dominant gradients of energy and environmental stability that increase toward the tropics and confound mechanistic interpretations. We test competing age and evolutionary diversification hypotheses, which may explain the diversification of this plant family over the past 70 million years. Our analyses show that the age hypothesis, which posits that clade richness is positively correlated with the ecological and evolutionary time since clade origin, fails to explain the richness gradient observed in Polygonaceae. However, an evolutionary diversification hypothesis is highly supported, with diversification rates being 3.5 times higher in temperate clades compared to tropical clades. We demonstrate that differences in rates of speciation, migration, and molecular evolution insufficiently explain the observed patterns of differential diversification rates. We suggest that reduced extinction rates in temperate clades may be associated with adaptive responses to selection, through which seed morphology and climatic tolerances potentially act to minimize risk in temporally variable environments. Further study is needed to understand causal pathways among these traits and factors correlated with latitude.

Leaf Mimicry: Chameleon-like Leaves in a Patagonian Vine.

Mimicry has evolved in plants for a number of traits, both floral and vegetative. The discovery of a vine that mimics the leaf shape of different hosts poses new questions about the function of leaf mimicry, interplant signalling and leaf development.

Focused ion beam scanning electron microscopy in biology.

Since the end of the last millennium, the focused ion beam scanning electron microscopy (FIB-SEM) has progressively found use in biological research. This instrument is a scanning electron microscope (SEM) with an attached gallium ion column and the 2 beams, electrons and ions (FIB) are focused on one coincident point. The main application is the acquisition of three-dimensional data, FIB-SEM tomography. With the ion beam, some nanometres of the surface are removed and the remaining block-face is imaged with the electron beam in a repetitive manner. The instrument can also be used to cut open biological structures to get access to internal structures or to prepare thin lamella for imaging by (cryo-) transmission electron microscopy. Here, we will present an overview of the development of FIB-SEM and discuss a few points about sample preparation and imaging.