Long-Term m5C Methylome Dynamics Parallel Phenotypic Adaptation in the CyanobacteriumTrichodesmium

Abstract

A major challenge in modern biology is understanding how the effects of short-term biological responses influence long-term evolutionary adaptation, defined as a genetically determined increase in fitness to novel environments. This is particularly important in globally important microbes experiencing rapid global change, due to their influence on food webs, biogeochemical cycles, and climate. Epigenetic modifications like methylation have been demonstrated to influence short-term plastic responses, which ultimately impact long-term adaptive responses to environmental change. However, there remains a paucity of empirical research examining long-term methylation dynamics during environmental adaptation in non-model, ecologically important microbes. Here, we show the first empirical evidence in a marine prokaryote for long-term m5C methylome modifications correlated with phenotypic adaptation to CO2, using a 7-year evolution experiment (1000+ generations) with the biogeochemically-important marine cyanobacterium Trichodesmium. We identify m5C methylated sites that rapidly changed in response to high (750 µatm) CO2 exposure and were maintained for at least 4.5 years of CO2 selection. After 7 years of CO2 selection, however, m5C methylation levels that initially responded to high-CO2 returned to ancestral, ambient CO2 levels. Concurrently, high-CO2 adapted growth and N2 fixation rates remained significantly higher than those of ambient CO2 adapted cell lines irrespective of CO2 concentration, a trend consistent with genetic assimilation theory. These data demonstrate the maintenance of CO2-responsive m5C methylation for 4.5 years alongside phenotypic adaptation before returning to ancestral methylation levels. These observations in a globally distributed marine prokaryote provide critical evolutionary insights into biogeochemically important traits under global change.

Two co‐dominant nitrogen‐fixing cyanobacteria demonstrate distinct acclimation and adaptation responses to cope with ocean warming

“…Both Trichodesmium and Crocosphaera genomes contain widespread, highly expressed non-coding spacers with unclear functions; the coding percentage in Trichodesmium IMS101 is $60%, while in Crocosphaera it is $75%-80% (Walworth et al, 2015). Recently, epigenetic modifications underlying phenotypic adaptation have also been described in Trichodesmium IMS101 (Walworth et al, 2017(Walworth et al, , 2020. More work is needed to examine whether genomic and epigenetic differences might account for the differing thermal responses of the two diazotrophs.…”

Bacterial Epigenomics: Coming of Age

“…(ii) are the observable changes in gene expression directly modulated by the acquisition of a particular subset of DNA methylation marks? Although recent studies have begun to provide insight into this topic ( 33 ), we will need to wait for further advances in long-read technologies applied to single-cell sequencing, in order to identify the missing pieces of what appears to be not only a complex puzzle of epigenetic-mediated persistence but also a promising gateway for the development of novel antibacterial drugs.…”

Advances in RNA Epigenetic Modifications in Hepatocellular Carcinoma and Potential Targeted Intervention Strategies

“…However, many studies have found that aberrant m5C modification may lead to a variety of abnormal conditions such as stress disorder, mitochondrial dysfunction, embryogenesis and neurodevelopmental abnormalities, and even tumor cell proliferation, migration, and tumorigenesis, etc. (Navarro et al, 2021;Walworth et al, 2021). Research in recent decades has found that multiple m5C methyltransferases are associated with some cancer phenotypes.…”