Are mutations truly random? is an online article of The Scientist. Genomes are not equal opportunity hosts of genetic mutations. Some genomic regions are more hospitable to mutations than others. The so called hot spots. This has piqued my curiosity as well as the curiosity of others. Why is this so? A study published in Proceedings of the Royal Society B calls attention to some intriguing ideas.

Even small SNP clusters are non-randomly distributed: is this evidence of mutational non-independence? is a paper authored by William Amos. The paper begins by noting that single nucleotide polymorphisms (SNPs) are very non-randomly distributed in the human genome. SNPs result when changes occur to one of the four nucleotides- A, T, C and G- within a sequence (if interested read details at the link). Amos was interested in exploring whether or not the likelihood of mutations increases with proximity to existing SNPs. From the paper:

HT: Clare

Besides genuine mutation hotspots, SNP clustering can arise in several ways. First, natural selection can modulate local variability along a chromosome to create non-randomness; balancing selection tends to create regions of increased variability (Charlesworth et al. 1997; Bubb et al. 2006), while purifying and directional selection tend to reduce variability (Oleksyk et al. 2008) and make neighbouring regions appear to have increased variability. Second, the time to most recent common ancestor (TMRCA) of genes within a population has a high variance. Consequently, each chromosome can be thought of as a linear patchwork of the products of recombination (Hudson & Kaplan 1995; Eriksson et al. 2002). Some regions will have deep ancestry and carry many SNPs, while those with shallow ancestry may carry fewer. Local recombination rate determines the grain of this patchwork and hence can potentially impact on cluster distribution and size. Third, some regions of the genome are likely to be relatively refractory to mutation or simply to have received less attention during SNP development, again causing other regions to seem to carry above-average variability.

The Scientist article quotes Maud Tenaillon, an evolutionary geneticist from the University of California:

The idea is quite interesting.

Still, the idea warrants further exploration.

It's nice to have a paper where you have an idea it gives you material to discuss something.

William Amos no doubt agrees. His parting sentence:

Elucidating exactly how mutational non-independence operates in real genomes will provide an exciting challenge for future research.

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