Muts Homolog 1 Connects Organelle Function and Epigenome Dynamics to Plant Development and Phenotypic Variation

Plastid and mitochondria function are critical for plant growth and development, and require the activity of organelle-targeted genes under nuclear control. MUTS HOMOLOG 1 (MSH1) is a nuclear-encoded, dual-targeted protein known to suppress mitochondrial genome recombination associated with cytoplasmic male sterility. However, MSH1 has additional roles in the plastid, where its loss results in developmental reprogramming encompassing a range of environmentally-sensitive phenotypes including delayed flowering, slower growth, variegation, and prolonged juvenility, with inheritance behaviors suggestive of an epigenetic contribution. Transcriptome profiling by RNA-seq identified pathways associated with a large component of the mutant phenotype in Arabidopsis thaliana, including phytohormone signaling, abiotic and biotic stress responses, photosynthetic function, and circadian rhythm, indicating that MSH1 function within organelles directly or indirectly influences these processes. Furthermore, small RNA-sequencing and bisulfite-sequencing confirmed the presence of genome-wide epigenetic changes, including altered 24-nt siRNA production and CG methylation, and increased CHG methylation over heterochromatic transposable elements. Additionally, msh1 mutants displayed disproportionately strong CHH hypomethylation from cold stress, demonstrating that they have an altered response to temperature-induced methylation changes. In plants, euchromatic or heterochromatic DNA methylation variation can be sufficient to generate phenotypic variation, and when Sorghum bicolor plants that have undergone MSH1-related reprogramming via RNAi suppression are backcrossed to wild-type plants, the resulting F 2 progeny shows enhanced variation for a number of phenotypic traits, including seed yield. Response to selection for this trait was variable but showed overall stability as a population, with some lineages having particularly higher yields than controls under poor environments, suggesting that MSH1 manipulation is a potential avenue for increased crop performance. Together, these results create an emerging model that places MSH1 within the intersection of organelle function, epigenetic regulation, and environmental interactions with plant development and phenotype