Regions in the genome with high CpG content are subject to frequent deamination, i.e., the mutation of a "C" to a "T" or a "G" to an "A" nucleotide. These mutations can have significant consequences, as both protein-coding genes and gene regulatory sequences are relatively rich in CpG sequences. Thus, a greater understanding of the mutational process can provide further insight into the workings of the human genome.
In order to discover whether spontaneous deamination of 5-methylcytosine (C) was a time- or replication-dependent process as it relates to CpG regions of the genome, Amanda Gaudreau worked with her Broad colleagues to compare and analyze over one million different SNPs in the dog and human genomes. Her research found that the rate of CpG mutation is significantly lower in the dog genome than in the human genome, suggesting that mutations caused by deamination occur as time-dependent processes rather than as replication-dependent processes. Because dogs have a shorter generation period, the CG content of the dog genome is higher than the human CG content, i.e., the shorter lifespan of the dog limits the depletion of CG dinucleotide content. This finding not only provides new insight into the evolutionary processes at work in forming the current human genome, but also gives scientists a glimpse into its future evolution.
"Amanda's research produced good suggestive data that we will be looking at more closely," said Mike Zody, a chief technologist in computational biology and bioinformatics, who served as Amanda's mentor."
Amanda Gaudreau, an MIT freshman, compared dog and human polymorphisms to identify mutation rates in the human genome.