Synonymous Codons as Potential Contributors to Chromatin Stability and Gene Body Methylation in Plants.

Synonymous codon sites were historically considered largely neutral; however, accumulating evidence indicates that codon usage may influence gene regulation, translation dynamics, and evolutionary fitness. In plants, gene body methylation (gbM) and chromatin-based stress memory represent stable epigenetic features whose underlying sequence determinants remain poorly understood. Here, we propose that synonymous codon architecture may contribute to chromatin stability in plant genomes through two complementary mechanisms. First, codon choice may influence the density and distribution of CG dinucleotides within coding regions, thereby shaping the substrate landscape for CG gene body methylation maintained by DNA methyltransferases. Second, synonymous codon usage may influence translation elongation kinetics, which may affect co-translational folding and post-translational modification dynamics of chromatin-associated proteins, particularly histones. Because histone proteins are highly conserved at the amino acid level, synonymous variation in histone genes may provide a powerful model system to detect regulatory constraints acting on coding sequences. We propose that selection acting on synonymous codons may therefore contribute not only to translational efficiency but also to the stability of epigenetic states and chromatin regulation. This perspective integrates codon usage bias, plant epigenomics, and chromatin biology and generates testable predictions regarding how coding sequence composition may influence gene body methylation patterns, chromatin stability, and long-term epigenetic inheritance.