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Compétition pour la transcription et évolution de l'expression génétique chez les diploïdes

Abstract : Non-coding sequences, that regulate gene expression, are as important as coding sequences to determine phenotypes. Many studies have identified the main forces affecting regulatory sequence evolution. Here, we theoretically identify a new selective force that may also play a role in this matter. Using multi-locus models, we show that stronger (activating more transcription) enhancers gain some benefit in having its associated gene copy more expressed than the homolog gene copy, controlled by a weaker homolog enhancer. Overexpressed gene copies are better purged from deleterious mutations, such that stronger enhancers get associated with a better genetic background. If recombination between the gene and the enhancer is low enough for this association to persist, enhancer strength selectively increases. Enhancer strength escalation does not necessarily lead to protein overproduction. Other regulators may indeed co-evolve to maintain optimal expression levels, provided that stabilizing selection allows for transitory sub-optimal expression levels. Implementing in the models different reproductive systems, we show that this new selective process does not necessarily lead to an enhancer strength escalation. When chromosomes are genetically isolated enough (little recombination, little outcrossing, selection for favorable genetic associations leads to chromosome divergence: one accumulates stronger enhancers and viable gene alleles, while the other accumulates weaker enhancers and deleterious gene mutations. For non-recombining clonal lineages, we expect gene expression to become haploid: for each gene, one copy is shut down and degenerates. Such divergence also applies to non-recombining sex chromosomes. We show that in such case, chromosome divergence leads to a shut down and degeneration of Y chromosome genes, and to an overexpression of genes located on X chromosomes. With our model, we propose a new theory to explain sex chromosome evolution after they stop recombining. Finally, we used divergence data between Mus musculus and Rattus norvegicus to find a signal that can only be explained by positive selection for stronger proximal enhancers. This signal is weak, but significant: this is the first empirical confirmation of enhancer strength escalation process we studied here.
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Submitted on : Monday, November 27, 2017 - 8:45:15 PM
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  • HAL Id : tel-01649871, version 1


Frédéric Fyon. Compétition pour la transcription et évolution de l'expression génétique chez les diploïdes. Génétique. Université Montpellier, 2016. Français. ⟨NNT : 2016MONTT131⟩. ⟨tel-01649871⟩



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