Research Outputs

Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2

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Open Access
Phenotypic plasticity as a facilitator of microbial evolution
(Oxford University Press (OUP), 2022) Santiago, E.; Moreno, D.F.; Acar, Murat; Faculty Member; School of Medicine; 384943
Tossed about by the tides of history, the inheritance of acquired characteristics has found a safe harbor at last in the rapidly expanding field of epigenetics. The slow pace of genetic variation and high opportunity cost associated with maintaining a diverse genetic pool are well-matched by the flexibility of epigenetic traits, which can enable low-cost exploration of phenotypic space and reactive tuning to environmental pressures. Aiding in the generation of a phenotypically plastic population, epigenetic mechanisms often provide a hotbed of innovation for countering environmental pressures, while the potential for genetic fixation can lead to strong epigenetic-genetic evolutionary synergy. At the level of cells and cellular populations, we begin this review by exploring the breadth of mechanisms for the storage and intergenerational transmission of epigenetic information, followed by a brief review of common and exotic epigenetically regulated phenotypes. We conclude by offering an in-depth coverage of recent papers centered around two critical issues: the evolvability of epigenetic traits through Baldwinian adaptive phenotypic plasticity and the potential for synergy between epigenetic and genetic evolution.
Open Access
Phenotypic selection during laboratory evolution of yeast populations leads to a genome-wide sustainable chromatin compaction shift
(Frontiers, 2022) Moreno, D.F.; Acar, Murat; Faculty Member; School of Medicine; 384943
In a previous study, we have shown how microbial evolution has resulted in a persistent reduction in expression after repeatedly selecting for the lowest P-GAL1-YFP-expressing cells. Applying the ATAC-seq assay on samples collected from this 28-day evolution experiment, here we show how genome-wide chromatin compaction changes during evolution under selection pressure. We found that the chromatin compaction was altered not only on GAL network genes directly impacted by the selection pressure, showing an example of selection-induced non-genetic memory, but also at the whole-genome level. The GAL network genes experienced chromatin compaction accompanying the reduction in P-GAL1-YFP reporter expression. Strikingly, the fraction of global genes with differentially compacted chromatin states accounted for about a quarter of the total genome. Moreover, some of the ATAC-seq peaks followed well-defined temporal dynamics. Comparing peak intensity changes on consecutive days, we found most of the differential compaction to occur between days 0 and 3 when the selection pressure was first applied, and between days 7 and 10 when the pressure was lifted. Among the gene sets enriched for the differential compaction events, some had increased chromatin availability once selection pressure was applied and decreased availability after the pressure was lifted (or vice versa). These results intriguingly show that, despite the lack of targeted selection, transcriptional availability of a large fraction of the genome changes in a very diverse manner during evolution, and these changes can occur in a relatively short number of generations.
Metadata only
Rationally reprogramming single-cell aging trajectories and lifespan through dynamic modulation of environmental inputs
(Cell Press, 2024) Smart M.; Moreno DF; Acar, Murat; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine
How do variations in nutrient levels influence cellular lifespan? A dynamical systems model of a core circuit involved in yeast aging suggests principles underlying lifespan extension observed at static and alternating glucose levels that are reminiscent of intermittent fasting regimens.