A Unifying Theory for GC3 Biology in Plants and Animals

There is a well-documented bias for cytosine and guanine at the third position in a subset of transcripts within a single organism; it is present in some plant species and warm-blooded vertebrates. We demonstrated that in certain organisms the amount of GC at the wobble position (GC3) can be used to distinguish two classes of genes. We highlight the following features of genes with high GC3content: they (1) provide more targets for methylation, (2) exhibit more variable expression, (3) more frequently possess certain transcription factor binding sites, (4) are predominant in certain classes of genes and (5) have a GC3 content that increases from 5'to 3'. These observations led us to formulate a hypothesis to explain GC3 bimodality in grasses and later extend it to other species. High levels of GC3 typify a class of genes regulated through DNA methylation or are a legacy of accelerated evolution through gene conversion.