Evolution of the G+C Content Frontier in the Rat Cytomegalovirus Genome

Within the 230138 bp of the rat cytomegalovirus (RCMV) genome, the G+C content changes abruptly at position 142644, constituting a G+C content frontier. To the left of this point, overall G+C content is 69.2%, and to the right it is only 47.6%. A region of extremely low G+C content (33.8%) is found in the 5 kb immediately to the right of the frontier, in which there are no predicted coding sequences. To the right of position 147501, the G+C content rises and predicted coding sequences reappear. However, these genes are much shorter (average 848bp, 50% G+C) than those in the left two-thirds of the genome (average 1462bp, 70% G+C). Whole genome alignment of several viruses indicates that the initial ultra-low G+C region appeared in the common ancestor of the genera Cytomegalovirus and Muromegalovirus, and that the lowering of G+C in the right third has been a subsequent process in the lineage leading to RCMV. The left two-thirds of RCMV has stop codon occurrences at 67.5% of their expected level, based on a modified Markov chain model of stop codon distribution, and the corresponding figure for the right third is 78%. Therefore, despite heavy mutation pressure, selective constraint has operated in the right third of the RCMV genome to maintain a degree of gene length unusual for such low G+C sequences.