Publications

The simultaneous typing of five-HLA loci at high resolution and the availability of pedigree data allowed us to characterize extended five-locus phased haplotypes in 124 Nigerian families and to compare the observed frequencies with those expected by an expectation-maximization algorithm for unphased data. Despite the occurrence of some frequent alleles at each locus (e.g. B*53:01, which is assumed to protect against Plasmodium falciparum), as many as 82% of the sampled individuals carry two unique five-locus haplotypes and only three extended haplotypes with frequency above 1% exhibit significant linkage disequilibrium. Although preliminary, these results reveal an extreme level of HLA diversity in the Nigerian population, which reflects both its multi-ethnic composition and the very ancient demographic history of African populations.

Homeotic genes are aligned on the chromosome in the order of the segments that they specify along the antero-posterior axis of the fly. In general the genes affecting the more posterior segments repress the more anterior genes, a phenomenon known as "posterior dominance". There is however a noticeable exception to this rule in the central nervous system of Drosophila melanogaster where the posterior Abd-B gene does not repress the immediately more anterior abd-A gene. Instead, abd-A repression is accomplished by a 92 kb-long ncRNA (the iab-8ncRNA) that is transcribed from the large inter-genic region between abd-A and Abd-B. This iab-8ncRNA encodes a microRNA to repress abd-A and also a second redundant repression mechanism acting in cis and thought to be transcriptional interference with the abd-A promoter. Using in situ hybridization, a previous work suggested that the iab8ncRNA transcript forms discrete foci restricted to the nuclear periphery and that this localization may be important for its function. In order to better characterize the intra-cellular localization of the iab-8ncRNA we used the MS2-MCP system, which allows fluorescent labeling of RNA in cells and relies on the interaction between GFP-tagged MS2 coat protein (MCP-GFP) and MS2 RNA stem loops. Our results indicate that the large foci seen in previous studies correspond to the site of iab8ncRNA transcription and that the foci seen may simply be an indication of the level of transcription at the locus. We find no evidence to suggest that this localization is important for its function on abd-A repression. We discuss the idea that the iab-8ncRNA may be a relic of a more general ancient mechanism of posterior dominance during the emergence of the hox clusters that was mediated by transcriptional interference.

Monothalamous (single-chambered) foraminifera comprise a poorly known group, the diversity of which is strongly underestimated according to environmental DNA surveys. The gross morphology of monothalamids offers few distinguishing features; their organic-walled or agglutinated tests are often very delicate and make isolation difficult. Here, we use an integrated taxonomic approach, including morphological and molecular analysis, to examine the diversity of monothalamids in a shallow subtidal area on the coast of Iceland. We report nine new phylotypes of single-chambered foraminifera distinguished by SSU rDNA sequences. Among them, we establish a new genus Flexammina and a new species Flexammina islandica, possessing a very pliable, finely agglutinated test capable of extreme shape transformations. According to molecular data, F. islandica belongs to the monothalamid clade M, which also includes the well-known genus Allogromia. In addition, we provide brief descriptions and illustrations of nine other monothalamous foraminifera isolated from the same area. Three of them are closely related to some unidentified environmental sequences and serve as the first microscopic documentation of these anonymous lineages.

The tetrapod vertebral column has become increasingly complex during evolution as an adaptation to a terrestrial life. At the same time, the evolution of the vertebral formula became subject to developmental constraints acting on the size of the cervical and thoraco-lumbar regions. In the course of our studies concerning the evolution of Hox gene regulation, we produced a transgenic mouse model expressing fish Hox genes, which displayed a reduced number of thoraco-lumbar vertebrae and concurrent sacral homeotic transformations. Here, we analyze this mutant stock and conclude that the ancestral, pre-tetrapodial Hox code already possessed the capacity to induce vertebrae with sacral characteristics. This suggests that alterations in the interpretation of the Hox code may have participated to the evolution of this region in tetrapods, along with potential modifications of the HOX proteins themselves. With its reduced vertebral number, this mouse stock violates a previously described developmental constraint, which applies to the thoraco-lumbar region. The resulting offset between motor neuron morphology, vertebral patterning and the relative positioning of hind limbs illustrates that the precise orchestration of the Hox-clock in parallel with other ontogenetic pathways places constraints on the evolvability of the body plan.

This paper presents a reconstruction of climatedriven environmental changes over the last millennium in Hornsund Fjord (Svalbard), based on sedimentological and micropalaeontological records. Our palaeo-investigation was supported by an analysis of foraminiferal ancient DNA (aDNA), focusing on the non-fossilized monothalamous species. The main climatic fluctuations during the last millennium were the Medieval Warm Period (MWP, AD 1000– 1600), the Little Ice Age (LIA, AD 1600–1900) and the modern warming (MW, AD 1900 to present). Our study indicates that the environmental conditions in Hornsund during the MWP and the early LIA (before ∼ AD 1800) were relatively stable. The beginning of the LIA (∼ AD 1600) was poorly evidenced by the micropalaeontological record but was well marked in the aDNA data by an increased proportion of monothalamous foraminifera, especially Bathysiphon sp. The early LIA (∼ 1600 to ∼ AD 1800) was marked by an increase in the abundance of sequences of Hippocrepinella hirudinea and Cedhagenia saltatus. In the late LIA (after ∼ AD 1800), the conditions in the fjord became glacierproximal and were characterized by increased meltwater out- flows, high sedimentation and a high calving rate. This coincided with an increase in the percentages of sequences of Micrometula sp. and Vellaria pellucidus. During the MW, the major glacier fronts retreated rapidly to the inner bays, which limited the iceberg discharge to the fjord’s centre and caused a shift in the foraminiferal community that was reflected in both the fossil and aDNA records.

Epithelial sheets, a synapomorphy of all metazoans but porifers, are present as 2 layers in cnidarians, ectoderm and endoderm, joined at their basal side by an extra-cellular matrix named mesoglea. In the Hydra polyp, epithelial cells of the body column are unipotent stem cells that continuously self-renew and concomitantly express their epitheliomuscular features. These multifunctional contractile cells maintain homeostasis by providing a protective physical barrier, by digesting nutrients, by selecting a stable microbiota, and by rapidly closing wounds. In addition, epithelial cells are highly plastic, supporting the adaptation of Hydra to physiological and environmental changes, such as long starvation periods where survival relies on a highly dynamic autophagy flux. Epithelial cells also play key roles in developmental processes as evidenced by the organizer activity they develop to promote budding and regeneration. We propose here an integrative view of the homeostatic and developmental aspects of epithelial plasticity in Hydra.

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection.

Functional brain-imaging techniques used in humans and animals, such as functional MRI and intrinsic optical signal (IOS) imaging, are thought to largely rely on neurovascular coupling and hemodynamic responses. Here, taking advantage of the well-described micro-architecture of the mouse olfactory bulb, we dissected the nature of odor-evoked IOSs. Using in vivo pharmacology in transgenic mouse lines reporting activity in different cell types, we show that parenchymal IOSs are largely independent of neurotransmitter release and neurovascular coupling. Furthermore, our results suggest that odor-evoked parenchymal IOSs originate from changes in light scattering of olfactory sensory neuron axons, mostly due to water movement following action potential propagation. Our study sheds light on a direct correlate of neuronal activity, which may be used for large-scale functional brain imaging.

Despite the availability of deep-sequencing techniques, genomic and transcriptomic data remain unevenly distributed across phylogenetic groups. For example, reptiles are poorly represented in sequence databases, hindering functional evolutionary and developmental studies in these lineages substantially more diverse than mammals. In addition, different studies use different assembly and annotation protocols, inhibiting meaningful comparisons. Here, we present the "Reptilian Transcriptomes Database 2.0," which provides extensive annotation of transcriptomes and genomes from species covering the major reptilian lineages. To this end, we sequenced normalized complementary DNA libraries of multiple adult tissues and various embryonic stages of the leopard gecko and the corn snake and gathered published reptilian sequence data sets from representatives of the four extant orders of reptiles: Squamata (snakes and lizards), the tuatara, crocodiles, and turtles. The LANE runner 2.0 software was implemented to annotate all assemblies within a single integrated pipeline. We show that this approach increases the annotation completeness of the assembled transcriptomes/genomes. We then built large concatenated protein alignments of single-copy genes and inferred phylogenetic trees that support the positions of turtles and the tuatara as sister groups of Archosauria and Squamata, respectively. The Reptilian Transcriptomes Database 2.0 resource will be updated to include selected new data sets as they become available, thus making it a reference for differential expression studies, comparative genomics and transcriptomics, linkage mapping, molecular ecology, and phylogenomic analyses involving reptiles. The database is available at www.reptilian-transcriptomes.org and can be enquired using a wwwblast server installed at the University of Geneva.