Lejzerowicz F, Esling P, Majewski W, Szczucinski W, Decelle J, Obadia C, Arbizu P M, Pawlowski J

Department of Genetics and Evolution, University of Geneva, , 1211 Geneve 4, Switzerland.

Deep-sea subsurface sediments are the most important archives of marine biodiversity. Until now, these archives were studied mainly using the microfossil record, disregarding large amounts of DNA accumulated on the deep-sea floor. Accessing ancient DNA (aDNA) molecules preserved down-core would offer unique insights into the history of marine biodiversity, including both fossilized and non-fossilized taxa. Here, we recover aDNA of eukaryotic origin across four cores collected at abyssal depths in the South Atlantic, in up to 32.5 thousand-year-old sediment layers. Our study focuses on Foraminifera and Radiolaria, two major groups of marine microfossils also comprising diverse non-fossilized taxa. We describe their assemblages in down-core sediment layers applying both micropalaeontological and environmental DNA sequencing approaches. Short fragments of the foraminiferal and radiolarian small subunit rRNA gene recovered from sedimentary DNA extracts provide evidence that eukaryotic aDNA is preserved in deep-sea sediments encompassing the last glacial maximum. Most aDNA were assigned to non-fossilized taxa that also dominate in molecular studies of modern environments. Our study reveals the potential of aDNA to better document the evolution of past marine ecosystems and opens new horizons for the development of deep-sea palaeogenomics.

Dietschi Q, Assens A, Challet L, Carleton A, Rodriguez I

Department of Genetics and Evolution, School of Medicine, University of Geneva, Switzerland.

In the mouse, most members of the FPR receptor family are expressed by vomeronasal sensory neurons. The neural circuitry corresponding to this class of chemical sensors is unknown. Taking advantage of the presence of FPR-rs3 on both vomeronasal dendrites and axonal fibers, we visualized the distribution of sensory cells expressing this member of the FPR family, and their corresponding axonal projections in the olfactory bulb. We found a rostrocaudal gradient of receptor choice frequency in the vomeronasal sensory neuroepithelium, and observed a convergence of FPR-rs3 axons into multiple, linked and deeply located glomeruli. These were homogenously innervated, and spatially restricted to the basal portion of the rostral accessory olfactory bulb. This organization, reminiscent of the one that characterizes axonal projections of V1R-expressing neurons, supports a role played by these receptors in the perception of semiochemicals.

Montavon T, Duboule D

National Research Centre 'Frontiers in Genetics', School of Life Sciences, Ecole Polytechnique Federale , Lausanne, Switzerland.

During development, a properly coordinated expression of Hox genes, within their different genomic clusters is critical for patterning the body plans of many animals with a bilateral symmetry. The fascinating correspondence between the topological organization of Hox clusters and their transcriptional activation in space and time has served as a paradigm for understanding the relationships between genome structure and function. Here, we review some recent observations, which revealed highly dynamic changes in the structure of chromatin at Hox clusters, in parallel with their activation during embryonic development. We discuss the relevance of these findings for our understanding of large-scale gene regulation.

Mack S J, Cano P, Hollenbach J A, He J, Hurley C K, Middleton D, Moraes M E, Pereira S E, Kempenich J H, Reed E F, Setterholm M, Smith A G, Tilanus M G, Torres M, Varney M D, Voorter C E, Fischer G...

Center for Genetics, Children's Hospital Oakland Research Institute, Oakland, CA, USA.

We have updated the catalogue of common and well-documented (CWD) human leukocyte antigen (HLA) alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, and -DPB1 loci in IMGT (IMmunoGeneTics)/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being 'common' (having known frequencies) and 707 as being 'well-documented' on the basis of ~140,000 sequence-based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program's bioinformatics web pages.

Loukou S., Huysecom E., Mayor A.

Recent archaeological survey conducted in Mali in the Guringin Valley, located in the Séno Plain, as well as at the top of the nearby Bandiagara Escarpment, has produced evidence allowing the characterisation of numerous settlement sites and locations at which prehistoric metallurgy was practised. The latter have abundant surface material, mainly consisting of ceramics that show a considerable diversity of decoration. Analysis of the surface pottery assemblages, complemented by that of stratified assemblages from a test pit at one of the sites, indicates important inter-site differences. The results suggest that water, a rare and precious resource in this sandy Sudano-Sahelian plain, attracted the settlement of different populations from Neolithic times to the present, with a particular density of occupation during the first and early second millennia AD. Groups of sites of similar modest size evoke the rural settlements of the Méma area of Mali more than the settlement clusters of the Inland Niger Delta, which are defined by large sites surrounded by satellite settlements in a context of proto-urbanisation.
Les prospections archéologiques menées au Mali dans la vallée du Guringin, située dans la plaine du Séno, et sur le sommet de la Falaise de Bandiagara toute proche, ont permis de mettre en évidence et de caractériser de nombreux sites d'habitat ainsi que des lieux d'activités métallurgiques. Ces derniers livrent en surface un matériel abondant, constitué majoritairement de fragments de céramiques aux décors très variés. L'analyse des assemblages céramiques de surface, complétée d'assemblages stratifiés issus d'un sondage sur l'un des sites, nous indique des différences intersites significatives. Les résultats suggèrent une occupation de diverses populations attirées par l'eau, rare et précieuse dans cette plaine sableuse soudano-sahlienne, et ceci du Néolithique à la période actuelle, avec une densité particulière durant le premier et le début du second millénaire ap. J.C. Les ensembles de sites de tailles modestes et équivalentes se rapprochent plus des regroupements de sites ruraux du Méma que des clusters du Delta intérieur du Niger, définis par un site principal entouré de satellites, caractéristiques d'un contexte de proto-urbanisation.

Sabbagh A, Marin J, Veyssiere C, Lecompte E, Boukouvala S, Poloni E S, Darlu P, Crouau-Roy B

Institut de Recherche pour le Developpement (IRD), UMR216-Mere et enfant face aux infections tropicales, Paris, France. audrey.sabbagh@ird.fr

BACKGROUND: The arylamine N-acetyltransferases (NATs) are a unique family of enzymes widely distributed in nature that play a crucial role in the detoxification of aromatic amine xenobiotics. Considering the temporal changes in the levels and toxicity of environmentally available chemicals, the metabolic function of NATs is likely to be under adaptive evolution to broaden or change substrate specificity over time, making NATs a promising subject for evolutionary analyses. In this study, we trace the molecular evolutionary history of the NAT gene family during the last ~450 million years of vertebrate evolution and define the likely role of gene duplication, gene conversion and positive selection in the evolutionary dynamics of this family. RESULTS: A phylogenetic analysis of 77 NAT sequences from 38 vertebrate species retrieved from public genomic databases shows that NATs are phylogenetically unstable genes, characterized by frequent gene duplications and losses even among closely related species, and that concerted evolution only played a minor role in the patterns of sequence divergence. Local signals of positive selection are detected in several lineages, probably reflecting response to changes in xenobiotic exposure. We then put a special emphasis on the study of the last ~85 million years of primate NAT evolution by determining the NAT homologous sequences in 13 additional primate species. Our phylogenetic analysis supports the view that the three human NAT genes emerged from a first duplication event in the common ancestor of Simiiformes, yielding NAT1 and an ancestral NAT gene which in turn, duplicated in the common ancestor of Catarrhini, giving rise to NAT2 and the NATP pseudogene. Our analysis suggests a main role of purifying selection in NAT1 protein evolution, whereas NAT2 was predicted to mostly evolve under positive selection to change its amino acid sequence over time. These findings are consistent with a differential role of the two human isoenzymes and support the involvement of NAT1 in endogenous metabolic pathways. CONCLUSIONS: This study provides unequivocal evidence that the NAT gene family has evolved under a dynamic process of birth-and-death evolution in vertebrates, consistent with previous observations made in fungi.

Rotger M, Glass T R, Junier T, Lundgren J, Neaton J D, Poloni E S, Van't Wout A B, Lubomirov R, Colombo S, Martinez R, Rauch A, Gunthard H F, Neuhaus J, Wentworth D, van Manen D, Gras L A, Schuitem...

Institute of Microbiology, University Hospital Center, University of Lausanne, Switzerland.

Background. HIV-positive persons have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods. In the general population, 23 common single nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on gender and cohort. Results. A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P=2.9x10-4). In the final, multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval, 1.05-2.04). This effect was similar to hypertension (OR=1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR=1.51; 95% CI, 1.16-1.96), diabetes (OR=1.66; 95% CI, 1.10-2.49), >1 year lopinavir exposure (OR=1.36; 95% CI, 1.06-1.73) and current abacavir treatment (OR=1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of non-genetic CAD risk factors, and did not change after adjustment for family history. Conclusions. In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Gligorov D, Sitnik J L, Maeda R K, Wolfner M F, Karch F

Department of Genetics and Evolution and NCCR Frontiers in Genetics, University of Geneva, Geneva, Switzerland.

In insects, products of the male reproductive tract are essential for initiating and maintaining the female post-mating response (PMR). The PMR includes changes in egg laying, receptivity to courting males, and sperm storage. In Drosophila, previous studies have determined that the main cells of the male accessory gland produce some of the products required for these processes. However, nothing was known about the contribution of the gland's other secretory cell type, the secondary cells. In the course of investigating the late functions of the homeotic gene, Abdominal-B (Abd-B), we discovered that Abd-B is specifically expressed in the secondary cells of the Drosophila male accessory gland. Using an Abd-B BAC reporter coupled with a collection of genetic deletions, we discovered an enhancer from the iab-6 regulatory domain that is responsible for Abd-B expression in these cells and that apparently works independently from the segmentally regulated chromatin domains of the bithorax complex. Removal of this enhancer results in visible morphological defects in the secondary cells. We determined that mates of iab-6 mutant males show defects in long-term egg laying and suppression of receptivity, and that products of the secondary cells are influential during sperm competition. Many of these phenotypes seem to be caused by a defect in the storage and gradual release of sex peptide in female mates of iab-6 mutant males. We also found that Abd-B expression in the secondary cells contributes to glycosylation of at least three accessory gland proteins: ovulin (Acp26Aa), CG1656, and CG1652. Our results demonstrate that long-term post-mating changes observed in mated females are not solely induced by main cell secretions, as previously believed, but that secondary cells also play an important role in male fertility by extending the female PMR. Overall, these discoveries provide new insights into how these two cell types cooperate to produce and maintain a robust female PMR.

Wenger Y, Galliot B

Department of Genetics and Evolution, Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland

BACKGROUND: Evolutionary studies benefit from deep sequencing technologies that generate genomic and transcriptomic sequences from a variety of organisms. Genome sequencing and RNAseq have complementary strengths. In this study, we present the assembly of the most complete Hydra transcriptome to date along with a comparative analysis of the specific features of RNAseq and genome-predicted transcriptomes currently available in the freshwater hydrozoan Hydra vulgaris. RESULTS: To produce an accurate and extensive Hydra transcriptome, we combined Illumina and 454 Titanium reads, giving the primacy to Illumina over 454 reads to correct homopolymer errors. This strategy yielded an RNAseq transcriptome that contains 48'909 unique sequences including splice variants, representing approximately 24'450 distinct genes. Comparative analysis to the available genome-predicted transcriptomes identified 10'597 novel Hydra transcripts that encode 529 evolutionarily-conserved proteins. The annotation of 170 human orthologs points to critical functions in protein biosynthesis, FGF and TOR signaling, vesicle transport, immunity, cell cycle regulation, cell death, mitochondrial metabolism, transcription and chromatin regulation. However, a majority of these novel transcripts encodes short ORFs, at least 767 of them corresponding to pseudogenes. This RNAseq transcriptome also lacks 11'270 predicted transcripts that correspond either to silent genes or to genes expressed below the detection level of this study. CONCLUSIONS: We established a simple and powerful strategy to combine Illumina and 454 reads and we produced, with genome assistance, an extensive and accurate Hydra transcriptome. The comparative analysis of the RNAseq transcriptome with genome-predicted transcriptomes lead to the identification of large populations of novel as well as missing transcripts that might reflect Hydra-specific evolutionary events.

Soshnikova N, Dewaele R, Janvier P, Krumlauf R, Duboule D

Department of Genetics and Evolution, University of Geneva, Sciences III, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland; Institute of Molecular Biology, Ackermannweg 4, 55116 Mainz, Germany.

The vertebrate body plan is characterized by an increased complexity relative to that of all other chordates and large-scale gene amplifications have been associated with key morphological innovations leading to their remarkable evolutionary success. Here, we use compound full Hox clusters deletions to investigate how Hox genes duplications may have contributed to the emergence of vertebrate-specific innovations. We show that the combined deletion of HoxA and HoxB leads to an atavistic heart phenotype, suggesting that the ancestral HoxA/B cluster was co-opted to help in diversifying the complex organ in vertebrates. Other phenotypic effects observed seem to illustrate the resurgence of ancestral (plesiomorphic) features. This indicates that the duplications of Hox clusters were associated with the recruitment or formation of novel cis-regulatory controls, which were key to the evolution of many vertebrate features and hence to the evolutionary radiation of this group.

Widmer V C, Georgiev B B, Mariaux J

Department of Invertebrates, Natural History Museum Geneva, PO Box 6434, 1211, Geneva 6, Switzerland.

A new species of hymenolepidid cestodes from Sephanoides sephaniodes (Trochilidae) found in Chile is described. The most characteristic features of Colibrilepis pusilla gen. nov., sp. nov. are the lack of rostellum, a cirrus sac with a thick-walled distal end (separated by a constriction) and protruding into genital atrium, a thick-walled saccular uterus filling entire median field of the gravid proglottis and the small number of eggs containing thick walled embryophores with polar swellings. Staphylepis is the most similar genus but differs in its apical structure because of the presence of a rudimentary rostellum. Moreover, molecular phylogenetic analyses show that Staphylepis and Colibrilepis are not sister taxa.

Galliot B

Department of Genetics and Evolution, University of Geneva, 30 quai Ernest Ansermet, CH-1211 Geneva-04, Switzerland. brigitte.galliot@unige.ch

The freshwater Hydra polyp provides a unique model system to decipher the mechanisms underlying adult regeneration. Indeed, a single cut initiates two distinct regenerative processes, foot regeneration on one side and head regeneration on the other side, the latter relying on the rapid formation of a local head organizer. Two aspects are discussed here: the asymmetric cellular remodeling induced by mid-gastric bisection and the signaling events that trigger head organizer formation. In head-regenerating tips (but not in foot ones), a wave of cell death takes place immediately, leading the apoptotic cells to transiently release Wnt3 and activate the beta-catenin pathway in the neighboring cycling cells to push them through mitosis. This process, which mimics the apoptosis-induced compensatory proliferation process deciphered in Drosophila larvae regenerating their discs, likely corresponds to an evolutionarily conserved mechanism, also at work in Xenopus tadpoles regenerating their tail or mice regenerating their skin or liver. How is this process generated in Hydra? Several studies pointed to the necessary activation of the extracellular signal-regulated kinase (ERK) 1-2 and mitogen-activated protein kinase (MAPK) pathways during early head regeneration. Indeed inhibition of ERK 1-2 or knockdown of RSK, cAMP response element-binding protein (CREB), and CREB-binding protein (CBP) prevent injury-induced apoptosis and head regeneration. The current scenario involves an asymmetric activation of the MAPK/CREB pathway to trigger injury-induced apoptosis in the interstitial cells and in the epithelial cells a CREB/CBP-dependent transcriptional activation of early genes essential for head-organizing activity as wnt3, HyBra1, and prdl-a. The question now is how bisection in the rather uniform central region of the polyp can generate this immediately asymmetric signaling.