It has been known for some time that the mutation varies across genomes at a variety of different scales. In humans this variation is most evident at the single nucleotide level, where the context of a site affects its rate of mutation; for example, a C followed by a G has a mutation rate 10-times the average mutation rate. We have recently shown, however that there is substantial variation in the mutation rate that is not associated with context effect (Hodgkinson and Eyre-Walker 2010a; Hodgkinson, et al. 2009). This is profoundly puzzling; how can a specific site have a higher mutation rate than the adjacent sites and this have nothing to do with sequence context. We have also produced some evidence that there is a mutational mechanism that generates two mutations, at the same site simultaneously (Hodgkinson and Eyre-Walker 2010b).

There is also variation in the mutation rate at a much larger scale. We are currently investigating at what scale this variation occurs in both the germ-line and somatic tissue (Hodgkinson, et al. 2012), and whether this impacts the genetic structure of inherited disease.

Hodgkinson A, Chen Y, Eyre-Walker A 2012. The large scale distribution of somatic mutations in cancer genomes. Human Mutation 33: 136-143.

Hodgkinson A, Eyre-Walker A 2010a. The genomic distribution and local context of coincident SNPs in human and chimpanzee. Genome Biol Evol 2: 547-557.

Hodgkinson A, Eyre-Walker A 2010b. Human triallelic sites: evidence for a new mutational mechanism? Genetics 184: 233-241.

10.1534/genetics.109.110510

Hodgkinson A, Ladoukakis E, Eyre-Walker A 2009. Cryptic Variation in the Human Mutation Rate. PLoS Biol 7: e27.