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G-quadruplexes (G4) are four stranded nucleic acid secondary structures that form in vitro and in vivo in certain guanine rich sequences, upon stable non-Watson-Crick pairing of four guanines and stacking. G4 biological functions remain elusive, as it is difficult to identify the physiological and molecular circumstances of their formation, stabilization, recognition and processing. Inherently, biological processes generating single-stranded nucleic acids are favourable circumstances. Here, we questioned G4 formation during replication in the yeast S. cerevisiae and describe its pathological consequences. For this, we inserted the G-quadruplex-forming CEB1 minisatellite sequence near the strong and early firing origin ARS305 in both orientations and monitored its behaviour. We show that CEB1 tandem repeats are tolerated in wild-type cells but are very frequently destabilized upon treatment with the PhenDC3 G4-ligand and in the specific absence of the Pif1 unwinding helicase activity but in a preferential orientation manner, namely when the G-rich strand is template of leading…

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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.