Etude de l’expression des gènes nycthéméraux à la lumière de l’évolution


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PhD thesis: a PhD thesis.
Etude de l’expression des gènes nycthéméraux à la lumière de l’évolution
Laloum David
Robinson-Rechavi Marc
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Université de Lausanne, Faculté de biologie et médecine
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Circadian clocks are now an important part of the understanding of biological systems. They are ubiquitous,
found in a wide range of biological processes, from molecular systems to behavior, and are also found almost
everywhere in nature: in animals, plants, bacteria and fungi. This thesis focuses on biological systems that
respond to factors oscillating on a 24-hour time scale.
The detection of genes expressed with a periodicity of 24 hrs remains a complicated aspect of analytical
work. We show that most detection methods are efficient only for strong signals and that outside of these
genes, the algorithms seem to detect rhythmic genes in a rather random way.
We have also tried to understand why genes have periodic variations in the amount of their RNA or their
protein they encode. Indeed, 20% to 50% of cyclically accumulated proteins (i.e. nycthemeral) are translated
from non-oscillating mRNAs, and conversely, there are many mRNAs that oscillate but not the proteins
they encode. Why is that? My results suggest that the nycthemeral variation of proteins concerns on average
highly expressed proteins, which remain on average costlier to produce for the cell (in terms of energy and
molecular material) compared to other proteins produced in a non-rhythmic way. Moreover, these rhythmic
proteins would be even more expensive to produce if the cell had to maintain constantly a sufficient high
effective level of these proteins to ensure the function. The costs of protein production are large enough to
be under natural selection, whereas the costs of mRNA production are not. So, why do cells periodically
produce some mRNAs? My results suggest that the periodic oscillation in mRNA quantity concerns genes
that have on average weaker cell-to-cell variability (noise) than genes with constant mRNA levels. Since
causality is not very clear, it is still possible that the rhythmicity of mRNAs may optimize the expression
precision for noise-sensitive functions over a period of time, repeatedly, every 24 hours. Finally, mRNA
rhythmicity concerns genes that have undergone a strong purifying selection. This strong purifying selection
does not seem to concern genes that have periodic protein levels, although there is insufficient data to really
go further in the formulation of an evolutionary explanation.
Overall, I suggest the hypothesis that rhythmicity of gene expression provides an adaptive advantage only to
species living in highly changing environments (over 24 hours). In such environments, i.e. for a large part of
marine and terrestrial ecosystems, it is possible that the rhythmicity of gene expression could have allowed
the preservation of complex and costly new properties that would otherwise have been eliminated.
The evolutionary trade-offs take into account the advantages provided by the function, its expression costs
and precision required, but maybe also the variability of expression leading to phenotypic diversity improving
adaptability in a fluctuating environment.
Circadian rhythm, nycthemeral rhythm, gene expression, tissue-specificity, evolutionary conservation, rhythm detection algorithms, benchmark, expression costs, noise, fitness, phenotype
Create date
07/12/2020 11:59
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28/01/2021 9:58
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