Since the first genome of the human being and other species was sequenced at the beginning of this century, several researchers have already warned that a phenomenon was repeating: the base pairs of adenines (A) and thymine (T) – so to speak, two of the four letters with which the DNA instruction manual is written – showed a well-defined periodicity. Specifically, the ratio of A / T pairs was higher every 10 base pairs .
This may sound like a very technical detail to the layman, but its importance should not be underestimated, because this pattern has been associated with the way in which DNA wraps around nucleosomes, a name given to the simplest compaction structure. of genetic material, around proteins called histones. In other words, it would affect the very nature of DNA, its “packaging” . Until now, the common opinion was to think that natural selection had favored A / T bases because it allows the DNA structure to fold more easily.
A team led by Núria López-Bigas, head of the Biomedical Genomics laboratory at the Institute for Research in Biomedicine (IRB Barcelona), has investigated a little more into the reason for this to happen and have found an alternative answer: damage processes and DNA repair could play a role in that mysterious sequence periodicity of genomes. Their study has been published in the journal Cell .
Steady rate mutations
After analyzing the distribution of mutations in more than 3,000 human tumors, López-Bigas’ team observed that they also accumulate at a rate of 10 base pairs in DNA. They then examined the mutations that are inherited from one generation to the next in both humans and plants and found the same periodicity .
According to IRB Barcelona scientists, as most of the mutations we receive are cytosines (C) –another nitrogenous base or letter of the genetic code– which are transformed into thymine (T), those areas of the DNA that are most prone to these alterations along the over millions of years they abound in pairs of A / T bases . The scientists subjected their hypotheses to a mathematical simulation, with positive results.
IRB Barcelona’s research not only helps us to better understand the particularities of our genome, but it also reveals the processes by which tumors acquire mutations. For this reason, the finding will allow to delve into the search for relevant mutations for the appearance of carcinogenic processes, another field in which the López-Bigas group is a reference.
Photo: A DNA molecule, made up of a double helix, surrounds histone proteins twice to form nucleosomes. The pink areas are those that are enriched by adenine / thymine base pairs (author: Iris Joval Granollers).
Más información: Oriol Pich, Ferran Muiños, Radhakrishnan Sabarinathan, Iker Reyes-Salazar, Abel Gonzalez-Perez, Nuria Lopez-Bigas. “Somatic and germline Mutation periodicity follow the orientation of the DNA minor groove around nucleosomas”. Cell (2018) doi: 10.1016/j.cell.2018.10.004
