A survey of genome wide sequence differences and comprehensive phenotypic differences of many isolates of Saccharomyces cerevisiae and S. paradoxus revealed an apparent paradox of low phenotypic diversity in S. paradoxus while having great genotypic diversity while the opposite is seen in S. cerevisiae. This paradox may be resolved by the understanding of adaptation of populations to their environments where complex traits are composed of linked antagonistic QTLs which can be broken up to reveal phenotypic diversity due to genetic interactions arising from outbreeding. An initial testable model will be described that may account for various observations.

Divergence in gene regulation can play a major role in evolution. I will discuss our phylogenetic framework to measure mRNA profiles in 15 yeast species from the phylum Ascomycota and reconstruct the evolution of their modular regulatory programs along a time course of growth on glucose over 300 million years. We found that modules have diverged proportionally to phylogenetic distance, with prominent changes in gene regulation accompanying changes in lifestyle and ploidy, especially in carbon metabolism. Gene duplication events significantly contribute to regulatory divergence, in particular close to their phylogenetic point of duplication. Paralogs from a whole genome duplication (WGD) event have a uniquely substantial contribution that extends over a longer span. Similar patterns occur when considering the evolution of the heat shock regulatory program measured in eight of the species, suggesting that these are general evolutionary principles.

Among the signals that control the epigenetic landscape, non-coding (nc)RNAs have been identified to play a major role but the generalization and the mechanisms of their activity are still poorly apprehended. Recent data using high-throughput technologies have profoundly changed our view on how the genomes are organized. Indeed transcriptome analyses have shown that large genomic regions are pervasively transcribed producing a broad variety of ncRNA which functions on the epigenome remain to be deciphered. Our recent works show that S. cerevisiae’s genome also supports production of non-coding protein large transcripts, which are strongly controlled by RNA decay pathways. Of specific interest are the lncRNA XUT that we described recently, mostly antisense to class II genes and associated with a consistent regulatory potential through epigenetic modifications. Interestingly, histone methyl transferase and histone deacetylase show strong interplays with large antisense ncRNA. Mechanistic insights of their regulatory activities will be presented and generalization of their…

Vibrios are bacteria responsible for a significant proportion of infections affecting marine invertebrates and represent the major cause of mortality in farmed marine species. They are able to colonize many habitats, exist in free-living planktonic seawater, adhered to surfaces within biofilms or associated with various marine hosts. This high adaptability is linked to their capacity to generate high-levels of genetic diversity, a significant proportion via lateral gene transfer (LGT). LGT is being increasingly recognized as a major driving force in the evolution of virulence traits in vibrio. In contrast to species that are pathogenic to humans little data is available regarding invertebrate pathogens. Recent advances in genomics alongside the domestication of marine invertebrates has provided an opportunity to close the gap in our understanding of vibrio pathogens infecting invertebrates, leading to new and original scientific questions.

The Nakaseomyces clade includes Candida glabrata, a major fungal pathogen of immuno-compromised patients, and five other species, two of which have recently also been identified as human opportunistic pathogens. The genome of C. glabrata was published in 2004, and we have recently sequenced the genomes of all other known species of the Nakaseomyces genus. This clade is much closer to Saccharomyces cerevisiae than to the major Candida clade that includes C. albicans. Indeed, the Nakaseomyces derive from the same ancestor as S. cerevisiae that underwent a whole-genome duplication event, and their genomes contain the elements needed for mating-type switching in S. cerevisiae. These consist of mating-type cassettes of both types in haploid genomes, and the HO gene, that encodes the endonuclease initiating the switching event. Nonetheless, the four “Candida” species within the clade have been described as asexual, and no mating-type switching has been directly observed in any species. All Nakaseomyces seem…

Ramlibacter tataouinensis, a new genus and species isolated a semi-arid region of South Tunisia, presents two different morphologies: cysts resistant to desiccation and highly motile rod-shaped cells. An unusual characteristic of its cell cycle is that it could make ‘rod-rod’ division but also ‘cysts-cysts’ division if water is available. Due to the strong correlation between light, heat and desiccation in desert environment, the effect of light on this cell cycle was studied. Blue light of low intensity strongly inhibits the cell division of Ramlibacter tataouinensis. Red light induces the ‘rod-rod’ division, while almost uniquely ‘cysts-cysts’ division occurs in the dark. Analysis of the genome reveals the presence of four blue light sensors and two red light sensors. The biochemical and biophysical properties of these two bacteriophytochromes are characterized. One of these bacteriophytochromes, RtaBphP2, absorbs maximally at 755 nm in the dark, typical to a Pfr form. The light-induced Pr form presents an absorption maximum…

The human Solute Carrier (SLC) transporters are important targets for drug development. Structure-based drug discovery for SLC transporters requires the description of their structure, dynamics, and mechanism of interaction with small molecule ligands and ions. The recent determination of atomic structures of human SLC transporters and their homologs, combined with improved computational power and prediction methods have led to an increased applicability of structure-based drug design methods for human SLC members. The utility of these methods will be illustrated by presenting case studies in which rational integration of computation and experiment was used to characterize SLC members that transport key nutrients and metabolites.