Patterns of genome diversity and composition are driven by recombination in humans

Genomic diversity and composition evolve under diverse and complex constraints such as demography, selection, mutations, or genomic rearrangements. However, the influence of these evolutionary forces and their interactions remain to be fully understood. In that prospect, I will present two projects based on the human genome. First, I will use a population genomics approach and show that purifying selection at linked sites (i.e. background selection) and GC-biased gene conversion (gBGC) together affect as much as 95% of the variants of our genome. Their magnitude are largely determined by variation in recombination rate and base composition and previous reconstruction of human demography based on synonymous sites for instance are thus likely biased by these two mechanisms. However, when focusing on genomic regions with recombination rates above 1.5 cM/Mb and mutation types (C↔G, A↔T), the effects of background selection and gBGC are minimal. I will advocate to use these neutral regions to reconstruct demographies.…

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Kinases and Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit”

Temporal control over protein phosphorylation and dephosphorylation is crucial for accurate chromosome segregation and forcompletion of the cell division cycle during exit from mitosis.Degradation of mitotic cyclins and activation of Cdk‐counteracting phosphatases lead to protein dephosphorylation. In budding yeast, theCdc14 phosphatase is thought to be a major regulator at this time, while in higher eukaryotes PP2A phosphatases take a dominant role. We usetime-resolved phosphoproteome analysis in budding yeast to evaluate the respective contributions of the kinases and phosphatase input. Thisreveals that successive inactivation of Cdks and of the mitotic kinase Polo contributes to order mitotic exit dephosphorylation events. Cdc14instructs the sequential pattern of phosphorylation changes, in part through its preferential recognition of serine-based cyclin-dependentkinase (Cdk) substrates. PP2ACdc55  in turn exhibit a broad substrate spectrum with some selectivity for phospho-threonines. Our resultsillustrate synergy and coordination between kinases and phosphatases to orchestrate the phosphoproteome by recognising some specific dockingmotifs, phosphoresidus and amino acid regions surrounding the phosphosite.

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Endothermy, marsupials and hibernation: a tale from three continents

Endothermic animals (i.e., birds and mammals) produce metabolic heat in their bodies in a way that allows them to maintain a near constant body temperature at values that are typically well above ambient temperature. This is an extravagant economy that requires these animals to maintain elevated energy budgets and spend a large part of their resources on basic maintenance. Several endotherms, however, become ectothermic (torpid) as an adaptive strategy to save energy during periods cold periods. However, the fitness-costs of this strategy could be important, as it entails important threats to organs and tissues due to the toxic effects of ROS production during hypoxia and reperfusion. The small South American marsupial, “monito del monte”  "Dromiciops gliroides", known as the missing link between the American and the Australian marsupials, is one of the few South American mammals known to hibernate. Expressing daily torpor and seasonal hibernation (=”opportunistic hibernation”), this species may provide crucial…

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Unraveling the mystery of orphan genes to understand the origins of genetic novelty

What explains the presence of a gene only in the genome of one species and not in any other? Species-specific protein-coding genes, also known as orphans, can arise "from scratch" from previously non-genic loci, through a process known as de novo gene emergence. How exactly the evolutionary transition from non-gene to functional gene unfolds is unclear. Can such de novo emerging genes increase an organism's fitness, and if so how? Orphan genes can also result from extensive sequence divergence of ancestral genes, which can eventually erase all similarity of a gene to its homologues in other species, a process even less well understood than de novo emergence. I will present novel findings which advance our understanding of both these evolutionary mechanisms and bring us a small step closer to a complete picture of the origins of genetic novelty.

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