Periodic Reporting for period 4 - EPICLINES (Elucidating the causes and consequences of the global pattern of epigenetic variation inArabidopsis thaliana)
Reporting period: 2022-12-01 to 2024-05-31
Epigenetics continues to fascinate, especially the notion that it blurs the line between “nature and nurture” and could make Lamarckian adaptation via the inheritance of acquired characteristics possible. That this is in principle possible is clear: in the model plant Arabidopsis thaliana (Thale cress), experimentally induced DNA methylation variation can be inherited and affect important traits. The question is whether this is important in nature. Recent studies of A. thaliana have revealed a pattern of correlation between levels of methylation and climate variables that strongly suggests that methylation is important in adaptation. However, somewhat paradoxically, the experiments also showed that much of the variation for this epigenetic trait appears to have a genetic rather than an epigenetic basis. This suggest that epigenetics may indeed be important for adaptation, but as part of a genetic mechanism that is currently not understood. The goal of this project was to determine whether the global pattern of methylation has a genetic or an epigenetic basis, and to use this information to elucidate the ultimate basis for the global pattern of variation: natural selection.
The main conclusion of the project was that the pattern of epigenetic variation is impossible to understand without understanding transposable element variation, which in turn is impossible to understand without independently sequencing and aligning population samples of genomes. Hence much of the effort of the project was devoted to this, a major undertaking. Experiments to answer the mechanisms of inheritance are only now being analyzed with this in mind.
The main conclusion of the project was that the pattern of epigenetic variation is impossible to understand without understanding transposable element variation, which in turn is impossible to understand without independently sequencing and aligning population samples of genomes. Hence much of the effort of the project was devoted to this, a major undertaking. Experiments to answer the mechanisms of inheritance are only now being analyzed with this in mind.
Work on understanding the genetic regulation of methylation variation is underway, using genome-wide association, as well a genetic crosses. Several papers have been published: the main conclusion is that the methylation is largely directly inherited with trans-acting modifiers playing a relatively minor role.
More importantly, we have confirmed our suspicion that the pattern is impossible to understand without understand transposon variation, and that this pattern, in turn, cannot be understood without full sequencing of multiple genome. A first paper describing such data using 27 genomes is under review, and we are working on the analysis of several hundred more genomes. This work represents a revolutionary change for population genetics.
More importantly, we have confirmed our suspicion that the pattern is impossible to understand without understand transposon variation, and that this pattern, in turn, cannot be understood without full sequencing of multiple genome. A first paper describing such data using 27 genomes is under review, and we are working on the analysis of several hundred more genomes. This work represents a revolutionary change for population genetics.
We expected to have roughly 200 genomes completely sequenced, and a nearly complete picture of transposon and DNA methylation variation. We also expected to have identified all major genetic determinants of methylation variation, and hopefully to have gained significant insight into environmental influences and evolutionary importance.
In collaboration with others, the first expectation has been met and exceeded, although the project was delayed because we underestimated how difficult it would be to analyze whole-genome polymorphism data, which pose a challenge to all of population genetics. With respect to the second expectation, we have mapped and identified several major genetic determinants, demonstrated that environmental influences the variation seen, however the evolutionary importance remains obscure.
In collaboration with others, the first expectation has been met and exceeded, although the project was delayed because we underestimated how difficult it would be to analyze whole-genome polymorphism data, which pose a challenge to all of population genetics. With respect to the second expectation, we have mapped and identified several major genetic determinants, demonstrated that environmental influences the variation seen, however the evolutionary importance remains obscure.