Genic GC3 Content and DNA Methylation Patterns in Plant and Animal Genomes’

Genic GC3 content and DNA methylation patterns in plant and animal genomes

GC3 is a measure of the GC-content in the third codon position. Because mutations in this position lead primarily to synonymous substitutions, the selective pressures affecting its composition are different from those acting on the first two codon positions, making it a valuable tool to study evolution.  In previous studies high GC3 was found to be associated with variable expression, higher frequency of upstream TATA boxes, and was also found to increase from 5' to 3' of genes. Moreover, GC3- rich genes are predominant in certain gene classes and are enriched in CpG dinucleotides that are potential targets for methylation. Based on these observations, we hypothesize that GC3 has a regulatory role involving methylation and gene expression. To test that hypothesis, we selected diverse taxa (rice, thale cress, bee, and human) that varied in the modality of their GC3 distribution and tested the association between GC3, DNA methylation and gene expression.  We examine the relationship between cytosine methylation levels and GC3, gene expression, genome signature, gene length, and other gene compositional features. We find a strong negative correlation (Pearson’s correlation coefficient r=-0.67, p-value <0.0001) between GC3 and genic CpG methylation. The comparison between 5’-3’ gradients of CG3-skew and genic methylation for the taxa in the study suggests interplay between gene-body methylation and transcription-coupled cytosine deamination effect.