Researchers at IRB Barcelona explain the origin of the "mysterious" periodicity in the genome

Researchers at IRB Barcelona explain the origin of the "mysterious" periodicity in the genome https://i1.wp.com/www.eresviral.com/wp-content/uploads/2018/11/Investigadores-del-IRB-Barcelona-explican-el-origen-de-la-misteriosa-periodicidad-en-el-genoma.jpg?fit=116%2C146&ssl=1

Researchers at IRB Barcelona explain the origin of the "mysterious" periodicity in the genome





Researchers at IRB Barcelona explain the origin of the "mysterious" periodicity in the genome


Scientists from the Institute of Biomedical Research (IRB Barcelona) (Catalonia, Spain) have offered an explanation of how a sequence in the genome sequence of all eukaryotes, from yeast to human, has been created throughout evolution. The results published in the journal Cell provide an alternative explanation to the one assumed so far by the international community and based on natural selection.



The researchers show that damage and repair processes in DNA can play a role in the generation of sequence periodicity in eukaryotic genomes. These processes are influenced by the orientation of the DNA structure when it is packaged inside the cell nucleus and this fact favors a certain composition, of a periodic nature, in the genomes of eukaryotes.



"The answer we give helps us understand better because our genome and that of other species is as we see it today," says Núria López-Bigas, head of the study and head of the Biomedical Genomics Laboratory at IRB Barcelona.



Since the sequence of the human genome and other genomes, such as the mouse or the vinegar fly, became available at the beginning of the 21st century, some researchers noticed the marked periodicity in the proportion of adenine base pairs (A) and thymes (T). The scientists observed that every 10 base pairs, the proportion of A / T pairs was higher.







The DNA molecule, formed by a double helix, surrounds the histones twice forming the nucleosomes. The pink areas are those that are enriched by base pairs of Adenine / Thymine (Author: Iris Joval Granollers)



This periodicity has been associated with how DNA is wrapped around nucleosomes (the simplest structure of DNA compaction, in which it is surrounded by proteins called histones). The reason given was that natural selection favored the appearance of A / T bases, because they provide greater flexibility to the structure of DNA, which facilitates that it can bend as it does around histones, forming nucleosomes .



Studying the distribution of mutations in more than 3,000 human tumors, the IRB Barcelona team observed that they also accumulate with a periodicity of 10 base pairs in the DNA.



"Investigating how tumor mutations are distributed throughout the genome in places where we discard presence of selection, we see a periodicity of 10 base pairs very marked in the DNA that is part of the nucleosomes", explains Oriol Pich, PhD student of IRB Barcelona with a grant from the Barcelona Institute of Science and Technology (BIST) and first author of the article.



This happens because the way in which the DNA is packaged in the nucleosome favors that there are zones more or less prone to take damage and to repair it, and as a result they are more or less prone to receive mutations.



Next, they studied the mutations that are inherited from one generation to another of both humans and plants, and realized that these inherited mutations also accumulate with a periodicity of 10 base pairs.



With this new discovery about the influence of nucleosomes on how mutations are generated in DNA, the researchers deduced that this fact could explain the creation of the mysterious periodicity of the genome of eukaryotes.



The IRB Barcelona scientists reasoned that since most of the mutations that we receive are cytosines (C) that turn into thymines (T), those regions more prone to receive mutations over millions of years have been converted into base pairs A / T in greater proportion.



To verify this reasoning, scientists have made a mathematical simulation of the evolution of the genome and have shown that, indeed, the periodicity of the human genome and the other eukaryotes could have been formed by this periodicity in the rate of mutations.



"To give this alternative explanation to the generation of the periodicity in the scientific community is very satisfactory", coincide Oriol Pich and Núria López-Bigas, who value this type of research. "It is a basic knowledge resulting from a research guided by curiosity that allows us to better understand what we observe in nature."



However, this research is not only an advance on what we know about our genome, but also allows us to understand the processes by which tumors acquire mutations. This has an implication in finding which mutations are relevant to the genesis of the tumors, another area in which the López-Bigas group is an expert.



This work is an example of the generation of new scientific knowledge based on basic research. The study was made possible thanks to the funding of the European Research Council (ERC) through a "Consolidator grant" project to Núria López-Bigas, of the Ministry of Science, through FEDER funds, and the Generalitat de Catalunya. (Source: IRB Barcelona)



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