Genetic differentiation of disjunct populations of the ants Formicaaquilonia and Formica lugubris in Europe.

The species Formica aquilonia and F. lugubris of the mound-building red wood ants have a disjunct boreoalpine distribution in Europe. The populations of F. aquilonia in Finland, Switzerland and the British Isles show little genetic differentiation, whereas the populations of F. lugubris show considerable differentiation. The Central European populations morphologically identified as F. lugubris can be genetically divided into two groups (here called types A and B). Type B is found in the Alps and the Jura mountains, and is genetically inseparable from F. aquilonia. Type A lives sympatrically with type B in the Jura mountains and is also found in the British Isles. Sympatry of the two types in the Jura shows that these are separate species. It remains open whether type B is morphologically atypical F. aquilonia or whether it is a separate species, perhaps with a past history of introgression between F. aquilonia and F. lugubris. The gene frequencies in the Finnish populations of F. lugubris differ from those of both types A and B. Genetic differences within F. lugubris indicate that the populations have evolved separately for a long time. The social structure of F. lugubris colonies also shows geographic variation. The nests in Finland and the British Isles seem to be mainly monogynous and monodomous, whereas the nests in Central Europe are polygynous and form polydomous colonies. F. aquilonia has polygynous and polydomous colonies in all populations studied.

Calorimetry of dehydrogenation and dangling-bond recombination in several hydrogenated amorphous silicon materials

Differential scanning calorimetry (DSC) was used to study the dehydrogenation processes that take place in three hydrogenated amorphous silicon materials: nanoparticles, polymorphous silicon, and conventional device-quality amorphous silicon. Comparison of DSC thermograms with evolved gas analysis (EGA) has led to the identification of four dehydrogenation processes arising from polymeric chains (A), SiH groups at the surfaces of internal voids (A'), SiH groups at interfaces (B), and in the bulk (C). All of them are slightly exothermic with enthalpies below 50 meV/H atoms , indicating that, after dissociation of any SiH group, most dangling bonds recombine. The kinetics of the three low-temperature processes [with DSC peak temperatures at around 320 (A),360 (A'), and 430°C (B)] exhibit a kinetic-compensation effect characterized by a linea relationship between the activation entropy and enthalpy, which constitutes their signature. Their Si-H bond-dissociation energies have been determined to be E (Si-H)0=3.14 (A), 3.19 (A'), and 3.28 eV (B). In these cases it was possible to extract the formation energy E(DB) of the dangling bonds that recombine after Si-H bond breaking [0.97 (A), 1.05 (A'), and 1.12 (B)]. It is concluded that E(DB) increases with the degree of confinement and that E(DB)>1.10 eV for the isolated dangling bond in the bulk. After Si-H dissociation and for the low-temperature processes, hydrogen is transported in molecular form and a low relaxation of the silicon network is promoted. This is in contrast to the high-temperature process for which the diffusion of H in atomic form induces a substantial lattice relaxation that, for the conventional amorphous sample, releases energy of around 600 meV per H atom. It is argued that the density of sites in the Si network for H trapping diminishes during atomic diffusion

Ecology and evolution of soil nematode chemotaxis.

Plants influence the behavior of and modify community composition of soil-dwelling organisms through the exudation of organic molecules. Given the chemical complexity of the soil matrix, soil-dwelling organisms have evolved the ability to detect and respond to these cues for successful foraging. A key question is how specific these responses are and how they may evolve. Here, we review and discuss the ecology and evolution of chemotaxis of soil nematodes. Soil nematodes are a group of diverse functional and taxonomic types, which may reveal a variety of responses. We predicted that nematodes of different feeding guilds use host-specific cues for chemotaxis. However, the examination of a comprehensive nematode phylogeny revealed that distantly related nematodes, and nematodes from different feeding guilds, can exploit the same signals for positive orientation. Carbon dioxide (CO(2)), which is ubiquitous in soil and indicates biological activity, is widely used as such a cue. The use of the same signals by a variety of species and species groups suggests that parts of the chemo-sensory machinery have remained highly conserved during the radiation of nematodes. However, besides CO(2), many other chemical compounds, belonging to different chemical classes, have been shown to induce chemotaxis in nematodes. Plants surrounded by a complex nematode community, including beneficial entomopathogenic nematodes, plant-parasitic nematodes, as well as microbial feeders, are thus under diffuse selection for producing specific molecules in the rhizosphere that maximize their fitness. However, it is largely unknown how selection may operate and how belowground signaling may evolve. Given the paucity of data for certain groups of nematodes, future work is needed to better understand the evolutionary mechanisms of communication between plant roots and soil biota.

Single loci with major effects in fire ants : the effects of the complementary sex-determining locus and the green beard supergene on gene expression

Etant données la complexité et la redondance des réseaux de gènes influençant de nombreux phénotypes, l'étude des rares cas d'un locus unique ayant des effets importants sur de nombreux phénotypes peut fournir des informations cruciales sur l'évolution des traits complexes. Nous avons séquencé le génome de la fourmi de feu Solenopsis invicta pour étudier comment l'expression des gènes détermine les effets majeurs et étendus de deux loci uniques sur le phénotype. Le premier locus concerne la détermination du sexe par le modèle des allèles complémentaires. Ce locus est connu pour déterminer le sexe chez tous les hyménoptères mais n'a été caractérisé que chez les abeilles. Les hétérozygotes pour ce locus se développent en reines diploïdes (ou ouvrières stériles) alors que les homozygotes se développent en mâles diploïdes incapables de produire du sperme et les hémizygotes en mâles haploïdes fertiles. Nous avons comparé l'expression des gènes entre les reines et les deux types de mâles au stade pupe, ainsi que 1 et 11 jours après l'émergence. Nous avons trouvé un changement prononcé de l'expression des gènes chez les mâles diploïdes, passant de très proche de celle des reines au stade pupe à identique aux mâles haploïdes 11 jours après l'émergence. Cela signifie que les mâles diploïdes sont condamnés à être stériles parce que les effets après émergence du locus de détermination du sexe ne per¬mettent pas d'effacer les effets de la ploïdie sur l'expression des gènes pendant le stade pupe, quand la spermatogénèse prend place. Le second locus aux effets majeurs que nous avons étudié est le supergène dit "green beard", qui consiste en 616 gènes couvrant 55% d'un chromosome (13 Mb) et est caractérisé par une absence de recombinaison entre les deux variants du supergène : "Social B" et "Social b" (SB et Sb). Au travers de l'effet "green beard", par lequel les ouvrières avec le supergène Sb discriminent favorablement les reines qui partagent ce supergène de façon perceptible, le génotype des reines fondatrices au niveau de ce supergène détermine l'organisation de la colonie : soit elle contient une seule reine SB/SB, soit plusieurs reines SB/Sb. Nous avons montré que le chromosome Sb a évolué comme le chromosome Y, accumulant probablement des allèles favorables dans des colonies avec plusieurs reines mais défavorables dans des colonies avec une seule reine (cf. gènes sexuellement antagonistes), ainsi que des transposons et des séquences répéti¬tives. Nous avons également montré que le polymorphisme du supergène cause de grandes différences d'expression chez les ouvrières et particulièrement les reines mais pas chez les mâles. Pour comprendre comment le polymorphisme du supergène chez les reines peut affecter l'organisation de la colonie, nous avons comparé l'expression entre les génotypes SB/SB et SB/Sb chez des reines vierges (1 et 11 jours) et des reines matures. Nous avons montré que les reines SB/SB sur-régulent des gènes impliqués dans la reproduction, expli-quant pourquoi elle grandissent plus rapidement et peuvent fonder des colonies de façon indépendante, tandis que les reines SB/Sb (qui ne peuvent fonder une nouvelle colonie) sur-régulent des gènes de signalement chimique qui affectent l'organisation des colonies par l'effet "green beard". - Given the complexity and redundancy of the gene networks that underlie many pheno- types, the study of rare cases of a single locus having major effects on many phenotypes can give powerful insights into the evolution of complex traits. We sequenced the genome of Solenopsis invicta fire ants to study how gene expression mediates the widespread major effects of two single loci on phenotype. The first is the complementary sex-determining locus, which is known to exist in most Hymenoptera despite being characterized only for honeybees. Heterozygotes at this locus become diploid queens (or sterile workers), homozy¬gotes become aspermic diploid males, and hemizygotes become fertile haploid males. We compared gene expression between queens and both types of males in pupae and 1 and 11 days after eclosion. We found a pronounced shift in gene expression in diploid males, from being nearly identical to queens as pupae to identical to haploid males 11 days after eclosion. This means that diploid males are condemned to sterility because the overriding effects of the sex locus after eclosion cannot undo the ploidy effects on expression during the pupal stage, when spermatogenesis must be completed. The second locus with major ef¬fects that we studied was the so-called "green beard" supergene, which consists of 616 genes encompassing 55% of one chromosome (13 Mb), without recombination between the two variants "Social B" and "Social b" (SB and Sb) supergene. Through the green beard effect, i.e. workers with the Sb supergene discriminating in favor of queens who perceptibly share this supergene, the founding queen's genotype at the supergene determines colony organi¬zation: either headed by a single SB/SB queen or many SB/Sb queens. We show that the Sb chromosome evolved like a Y-chromosome, probably accumulating alleles beneficial in multi-queen colonies but disadvantageous in single-queen colonies (cf. sexually antagonistic genes), as well as transposons and repetitive sequences. We also show that the polymor¬phism of the supergene causes widespread expression differences in workers and especially queens but not in males. To understand how the polymorphism at the supergene in queen can transform colony organization, we compared the expression between SB/SB and SB/Sb virgin queens (1 and 11 days) and mother queens. We show that SB/SB queens up-regulate genes involved in reproduction, explaining why they mature faster and can found colonies independently, while SB/Sb queens (which cannot found colonies) up-regulate chemical signaling genes that can transform colonies through the green beard effect.

Molecular characterization of Unc5CL/ZUD

Résumé : Au cours de l'évolution, les organismes multicellulaires ont développé le système immunitaire afin de pouvoir se défendre contre les pathogènes tel que les bactéries, les virus, et les parasites. La réponse immunitaire doit être finement régulée par différentes voies de signalisation moléculaire, afin d'assurer une efficacité optimale, et d'éviter des dommages tissulaires indésirables. Les résultats expérimentaux décrits dans ce manuscrit, mettent en évidence que la protéine Unc5CL, qui contient un death domain (DD), est impliquée dans la régulation de la réponse immunitaire des muqueuses. Il a été démontré que cette protéine contient aussi un domaine transmembranaire de type III dans sa partie N-terminale, permettant ainsi de l'ancrer et d'exposer sa partie C-terminale dans le cytosol, un prérequis pour la signalisation dans ce compartiment cellulaire. De plus, cette protéine a la capacité d'activer le facteur de transcription NFxB, qui joue un rôle important dans le système immunitaire, ainsi que dans d'autres processus cellulaires essentiels. Le profil transcriptionnel révèle que l'activation de NF-κB induite par Unc5CL conduit principalement à une réponse inflammatoire, qui se caractérise par la production de diverses chimiokines (e.g. CXCL-1, IL-8 et CCL20). Il a également été démontré que Unc5CL requiert les mêmes molécules qui sont utilisées dans la voie de signalisation des récepteurs de la famille toll et de l'interleukine-1. De manière similaire à leur protéine adaptatrice MyD88, Unc5CL a la capacité de recruter, via une interaction homotypique DD-DD, les kinases IRAK1 et IRAK4 qui contiennent elles aussi un DD, permettant ainsi au signal d'être transmis. La production d'un anticorps polyclonal contre le DD de Unc5CL a permis d'identifier des lignées cellulaires et des tissus exprimant cette protéine, ainsi que de déterminer sa localisation sub-cellulaire. Unc5CL a été détecté dans les cellules de la muqueuse utérine et intestinale, ainsi que dans une lignée cellulaire issue d'un adénocarcinome colorectal humain, les CaCo-2. Dans chacun de ces cas, Unc5CL a été principalement détectée au niveau apical des cellules épithéliales polarisées. De manière similaire à PIDD, une protéine impliquée dans la réponse aux dommages à l'ADN, et au constituant des pores nucléaires Nup98, Unc5CL est constitutivement clivé de manière autoprotéolytique, au niveau d'un site HFS. Il est intéressant d'observer que les deux fragments ainsi générés restent fortement associés l'un à l'autre après clivage. Finalement, un criblage protéomique pour identifier un partenaire d'interaction, a mis en évidence l'ubiquitin ligase E3 ITCH, qui régule de manière négative Unc5CL en augmentant sa dégradation. Summary : Multicellular organisms have evolved the immune system in order to defend themselves against pathogens such as bacteria, viruses and eukaryotic parasites. Immune responses have to be tightly orchestrated by signaling mechanisms to achieve optimal effectiveness and minimal tissue damage. The experimental results in this thesis manuscript provide evidence that the death domain (DD)-containing protein Unc5CL might be involved in the regulation of mucosal immune responses. It could be shown that the protein contains an N-terminal type-III transmembrane domain that anchors the protein with its C-terminus exposed to the cytosol, a prerequisite for signaling events in this compartment. Furthermore, the protein has the capacity to activate the transcription factor NF-κB, which plays an important role in the immune system as well as in other essential cellular processes. Transcriptional profiling revealed that Unc5CL-mediated activation of NF-κB mainly leads to an inflammatory response, characterized by the production of chemokines (e.g. CXCL-l, IL-8 and CCL20). Furthermore, it could be shown that Unc5CL requires the same downstream signaling molecules as the evolutionarily ancient tolUinterleukin-1 receptor family. Similar to their adapter protein MyD88, Unc5CL has the capacity to recruit the DD-containing kinases IRAKI and IRAK4 for signaling and can interact with these proteins via homotypic DD-DD interactions. Generation of polyclonal antibodies raised against the DD of Unc5CL allowed the identification of cell lines and tissues that express the endogenous protein as well as to confine its subcellular localization. Unc5CL was detected in primary mucosal uterine and intestinal epithelial cells as well as in the human colorectal adenocarcinoma cell line CaCo-2. In all cases, the protein was mainly localized to the apical face of these polarized epithelial cells. Similar to PIDD, a protein critically involved in responses to DNA damage, and the nuclear pore component Nup98, Unc5CL is constitutively autoproteolytically processed at an HFS site. Interestingly, the two generated cleavage fragments remain tightly associated after processing. Finally, a proteomics screen for interaction partners identified the E3 ubiquitin ligase ITCH as a negative regulator of Unc5CL by targeting the protein for degradation.

Life-history consequences of adaptation to larval nutritional stress in Drosophila.

Many animal species face periods of chronic nutritional stress during which the individuals must continue to develop, grow, and/or reproduce despite low quantity or quality of food. Here, we use experimental evolution to study adaptation to such chronic nutritional stress in six replicate Drosophila melanogaster populations selected for the ability to survive and develop within a limited time on a very poor larval food. In unselected control populations, this poor food resulted in 20% lower egg-to-adult viability, 70% longer egg-to-adult development, and 50% lower adult body weight (compared to the standard food on which the flies were normally maintained). The evolutionary changes associated with adaptation to the poor food were assayed by comparing the selected and control lines in a common environment for different traits after 29-64 generations of selection. The selected populations evolved improved egg-to-adult viability and faster development on poor food. Even though the adult dry weight of selected flies when raised on the poor food was lower than that of controls, their average larval growth rate was higher. No differences in proportional pupal lipid content were observed. When raised on the standard food, the selected flies showed the same egg-to-adult viability and the same resistance to larval heat and cold shock as the controls and a slightly shorter developmental time. However, despite only 4% shorter development time, the adults of selected populations raised on the standard food were 13% smaller and showed 20% lower early-life fecundity than the controls, with no differences in life span. The selected flies also turned out less tolerant to adult malnutrition. Thus, fruit flies have the genetic potential to adapt to poor larval food, with no detectable loss of larval performance on the standard food. However, adaptation to larval nutritional stress is associated with trade-offs with adult fitness components, including adult tolerance to nutritional stress.

Sib mating without inbreeding in the longhorn crazy ant.

Sib matings increase homozygosity and, hence, the frequency of detrimental phenotypes caused by recessive deleterious alleles. However, many species have evolved adaptations that prevent the genetic costs associated with inbreeding. We discovered that the highly invasive longhorn crazy ant, Paratrechina longicornis, has evolved an unusual mode of reproduction whereby sib mating does not result in inbreeding. A population genetic study of P. longicornis revealed dramatic differences in allele frequencies between queens, males and workers. Mother-offspring analyses demonstrated that these allele frequency differences resulted from the fact that the three castes were all produced through different means. Workers developed through normal sexual reproduction between queens and males. However, queens were produced clonally and, thus, were genetically identical to their mothers. In contrast, males never inherited maternal alleles and were genetically identical to their fathers. The outcome of this system is that genetic inbreeding is impossible because queen and male genomes remain completely separate. Moreover, the sexually produced worker offspring retain the same genotype, combining alleles from both the maternal and paternal lineage over generations. Thus, queens may mate with their brothers in the parental nest, yet their offspring are no more homozygous than if the queen mated with a male randomly chosen from the population. The complete segregation of the male and female gene pools allows the queens to circumvent the costs associated with inbreeding and therefore may act as an important pre-adaptation for the crazy ant's tremendous invasive success.

Origins and functional evolution of Y chromosomes across mammals.

Y chromosomes underlie sex determination in mammals, but their repeat-rich nature has hampered sequencing and associated evolutionary studies. Here we trace Y evolution across 15 representative mammals on the basis of high-throughput genome and transcriptome sequencing. We uncover three independent sex chromosome originations in mammals and birds (the outgroup). The original placental and marsupial (therian) Y, containing the sex-determining gene SRY, emerged in the therian ancestor approximately 180 million years ago, in parallel with the first of five monotreme Y chromosomes, carrying the probable sex-determining gene AMH. The avian W chromosome arose approximately 140 million years ago in the bird ancestor. The small Y/W gene repertoires, enriched in regulatory functions, were rapidly defined following stratification (recombination arrest) and erosion events and have remained considerably stable. Despite expression decreases in therians, Y/W genes show notable conservation of proto-sex chromosome expression patterns, although various Y genes evolved testis-specificities through differential regulatory decay. Thus, although some genes evolved novel functions through spatial/temporal expression shifts, most Y genes probably endured, at least initially, because of dosage constraints.

Eosinophilic oesophagitis: latest intelligence.

Eosinophilic oesophagitis (EoE), first described in the early 1990s, has rapidly evolved as a distinctive chronic inflammatory oesophageal disease with increasing incidence and prevalence in the westernized countries. Currently, EoE represents the main cause of dysphagia in adult patients. This disease is more prevalent in males and is frequently associated with allergies. The diagnosis is established based on the presence of oesophageal symptoms and dense eosinophilic oesophageal infiltration once other conditions leading to oesophageal eosinophilia are excluded. It is currently under discussion to what extent and by which methods allergic testing should be performed. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically. Especially in children, elimination diets can have similar efficacy as topical corticosteroids. Oesophageal dilation of EoE-induced oesophageal strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies are as yet defined. Cite this as: A. M. Schoepfer, D. Simon and A. Straumann, Clinical & Experimental Allergy, 2011 (41) 630-639.

The genomic impact of 100 million years of social evolution in seven ant species.

Ants (Hymenoptera, Formicidae) represent one of the most successful eusocial taxa in terms of both their geographic distribution and species number. The publication of seven ant genomes within the past year was a quantum leap for socio- and ant genomics. The diversity of social organization in ants makes them excellent model organisms to study the evolution of social systems. Comparing the ant genomes with those of the honeybee, a lineage that evolved eusociality independently from ants, and solitary insects suggests that there are significant differences in key aspects of genome organization between social and solitary insects, as well as among ant species. Altogether, these seven ant genomes open exciting new research avenues and opportunities for understanding the genetic basis and regulation of social species, and adaptive complex systems in general.

The Smartcanula: a new tool for remote access perfusion in limited access cardiac surgery.

Devices for venous cannulation have seen significant progress over time: the original, rigid steel cannulas have evolved toward flexible plastic cannulas with wire support that prevents kinking, very thin walled wire wound cannulas allowing for percutaneous application, and all sorts of combinations. In contrast to all these rectilinear venous cannula designs, which present the same cross-sectional area over their entire intravascular path, the smartcanula concept of "collapsed insertion and expansion in situ" is the logical next step for venous access. Automatically adjusting cross-sectional area up to a pre-determined diameter or the vessel lumen provides optimal flow and ease of use for both, insertion and removal. Smartcanula performance was assessed in a small series of patients (76 +/- 17 kg) undergoing redo procedures. The calculated target pump flow (2.4 L/min/m2) was 4.42 +/- 61 L/ min. Mean pump flow achieved during cardiopulmonary bypass was 4.84 +/- 87 L/min or 110% of the target. Reduced atrial chatter, kink resistance in situ, and improved blood drainage despite smaller access orifice size, are the most striking advantages of this new device. The benefits of smart cannulation are obvious in remote cannulation for limited access cardiac surgery, but there are many other cannula applications where space is an issue, and that is where smart cannulation is most effective.

Entrained macrocryst minerals as a key to the source region of olivine nephelinites: Humberg, Kaiserstuhl, Germany

Olivine nephelinites commonly contain macrocrysts of olivine and clinopyroxene. Some of these macrocrysts might represent fragments of the source region of the host magma transported to the Earth surface. If this hypothesis is correct these fragments can be used to characterize the composition of the source region and to put constraints on the magma generation process. In this study, we investigate the origin of macrocrysts and mineral aggregates from an olivine nephelinite from the Kaiserstuhl, Germany. We focus on clinopyroxenes (Cpx), which can be divided into three groups. Cpx I is relict Cpx from aggregates with deformed olivine that is depleted in Ca and characterized by strong light rare earth element (LREE) fractionation, low Ti/Eu and negative high field strength element (HFSE) anomalies. Its geochemical signature is consistent with formation by carbonatite metasomatism and with equilibration in the Presence of orthopyroxene. Cpx II is Ca-rich Cpx, forming both aggregates with deformed olivine and individual macrocrysts. The LREE, as for Cpx I, are strongly fractionated. Convex REE patterns may be present. The depletion in HFSE is less pronounced. Cpx III is oscillatory zoned Cpx phenociysis showing enrichment in Ca, convex REE patterns and no HFSE anomalies. The transition in the trace element abundances between the Cpx of the three groups is gradual. However, Cpx I and H did not crystallize from the host magma, as demonstrated by the presence of kink-bands and undulose extinction in the associated olivine and by the composition of alkali aluminosilicate glass inclusions in Cpx H. Based on the Cpx relationships, we interpret the studied suite of macrocrysts and mineral aggregates as a mixture of disintegrated fragments of the source region of the host olivine nephelinite. The process of melt generation was multi-stage. A primary carbonatite melt ascending from deeper levels in the mantle, probably from the dolomite-garnet peridotite stability field, reacted with mantle peridotite along the solidus ledge in the system lherzolite-CO2 (< 20-22 kbar) and started to crystallize carbonate minerals. Because of its low solidus temperature, the resulting carbonate-wehrlite assemblage melted incongruently with the formation of additional clinopyroxene. The carbonatite melt evolved during crystallization of carbonate minerals and concomitant incongruent melting of the carbonate-wehrlite, accompanied by the segregation of incipient alkali aluminosilicate melts. As a consequence of fast reaction rates in the presence of a carbonatite melt, this process probably took place under disequilibrium conditions. Further melting of the assemblage wehrlite + alkali aluminosilicate melt led to the generation of the olivine nephelinite magma. It entrained fragments of the wehrlite and brought them to the surface.

Famílies immigrades i escoles: dinàmiques de relació a Catalunya

A Catalunya els discursos acadèmics i de l'administració han anat evolucionant fins que s'han imposat aquells que apunten a que la relació entre l'escola, la família i l'entorn és clau per l'èxit escolar de l'alumnat i el bon funcionament del sistema educatiu. Malgrat aquesta evolució, en la pràctica el canvi és lent i, sovint, complicat, donat que apareixen resistències en les dues institucions, família i escola, degut a que fins avui sempre s'ha mantingut una relació marcada pel desequilibri de poder. El nostre treball teòric i, sobretot, empíric s'ha centrat en la relació entre la família immigrada i l'escola a Catalunya. Com es presentarà, la creació del que hem anomenat dinàmiques positives de relació i comunicació en els centres escolars es troba condicionada per les actituds i els comportaments dels equips directius, els professionals i les famílies, tot i que també l'espai físic en que es donen aquestes relacions és important. Respecte a la organització del centre hem destacat el papel de l'equip directiu. Diferenciant una models de gestió observem aquells més facilitadors de la relació i la comunicació amb i entre les famílies i aquells més desincentivadors. Això sí, sempre s'ha de tenir en compte les actituds dels docents i de les famílies que són múltiples i complexes.

Molecular changes underlying mammalian phenotypic innovation

Mammals are characterized by specific phenotypic traits that include lactation, hair, and relatively large brains with unique structures. Individual mammalian lineages have, in turn, evolved characteristic traits that distinguish them from others. These include obvious anatom¬ical differences but also differences related to reproduction, life span, cognitive abilities, be¬havior. and disease susceptibility. However, the molecular basis of the diverse mammalian phenotypes and the selective pressures that shaped their evolution remain largely unknown. In the first part of my thesis, I analyzed the genetic factors associated with the origin of a unique mammalian phenotype lactation and I studied the selective pressures that forged the transition from oviparity to viviparity. Using a comparative genomics approach and evolutionary simulations, I showed that the emergence of lactation, as well as the appear¬ance of the casein gene family, significantly reduced selective pressure on the major egg-yolk proteins (the vitellogenin family). This led to a progressive loss of vitellogenins, which - in oviparous species - act as storage proteins for lipids, amino acids, phosphorous and calcium in the isolated egg. The passage to internal fertilization and placentation in therian mam¬mals rendered vitellogenins completely dispensable, which ended in the loss of the whole gene family in this lineage. As illustrated by the vitellogenin study, changes in gene content are one possible underlying factor for the evolution of mammalian-specific phenotypes. However, more subtle genomic changes, such as mutations in protein-coding sequences, can also greatly affect the phenotypes. In particular, it was proposed that changes at the level of gene reg¬ulation could underlie many (or even most) phenotypic differences between species. In the second part of my thesis, I participated in a major comparative study of mammalian tissue transcriptomes, with the goal of understanding how evolutionary forces affected expression patterns in the past 200 million years of mammalian evolution. I showed that, while com¬parisons of gene expressions are in agreement with the known species phylogeny, the rate of expression evolution varies greatly among lineages. Species with low effective population size, such as monotremes and hominoids, showed significantly accelerated rates of gene expression evolution. The most likely explanation for the high rate of gene expression evolution in these lineages is the accumulation of mildly deleterious mutations in regulatory regions, due to the low efficiency of purifying selection. Thus, our observations are in agreement with the nearly neutral theory of molecular evolution. I also describe substantial differences in evolutionary rates between tissues, with brain being the most constrained (especially in primates) and testis significantly accelerated. The rate of gene expression evolution also varies significantly between chromosomes. In particular, I observed an acceleration of gene expression changes on the X chromosome, probably as a result of adaptive processes associated with the origin of therian sex chromosomes. Lastly, I identified several individual genes as well as co-regulated expression modules that have undergone lineage specific expression changes and likely under¬lie various phenotypic innovations in mammals. The methods developed during my thesis, as well as the comprehensive gene content analyses and transcriptomics datasets made available by our group, will likely prove to be useful for further exploratory analyses of the diverse mammalian phenotypes.

Comparison of splice sites in mammals and chicken

We have carried out an initial analysis of the dynamics of the recent evolution of the splice-sites sequences on a large collection of human, rodent (mouse and rat), and chicken introns. Our results indicate that the sequences of splice sites are largely homogeneous within tetrapoda. We have also found that orthologous splice signals between human and rodents and within rodents are more conserved than unrelated splice sites, but the additional conservation can be explained mostly by background intron conservation. In contrast, additional conservation over background is detectable in orthologous mammalian and chicken splice sites. Our results also indicate that the U2 and U12 intron classes seem to have evolved independently since the split of mammals and birds; we have not been able to find a convincing case of interconversion between these two classes in our collections of orthologous introns. Similarly, we have not found a single case of switching between AT-AC and GT-AG subtypes within U12 introns, suggesting that this event has been a rare occurrence in recent evolutionary times. Switching between GT-AG and the noncanonical GC-AG U2 subtypes, on the contrary, does not appear to be unusual; in particular, T to C mutations appear to be relatively well tolerated in GT-AG introns with very strong donor sites.