A new study published in the recent issue of Nature Genetics shows that error surveillance and repair mechanisms show higher efficiency in the protein coding region of the genome.

The basic structure of genes comprises exons and introns. Exons are genetic sequences that code information for the production of proteins, whereas introns do not. Exons are largely conserved between species, for example, humans, mice, and worms have similar exons. The scientific explanation for this similarity is that exons are critical regions for the survival of an organism and therefore mutations in these regions may lead to lethal phenotypes.  

The Biomedical Genomics lab head Núria López-Bigas explained that negative selection is not the only key factor responsible for maintaining exons between species. For the first time, the researchers demonstrated that the exon regions get repaired more, and it has very few numbers of mutation compared to the other areas.

During DNA replication, the molecule called polymerase assembles the nucleotide-like blocks while maintaining the original sequence, but sometimes errors can occur by incorporating the wrong nucleotide. The DNA mismatch repair mechanism is used to correct these.

The study involved the analysis of colorectal tumors in which the polymerase carries a mutation, converting it to an error-prone polymerase. Thus, these tumors carry a large number of mutations. The researchers compared the numbers of mutations in exons and introns, and they found exons to have less than the expected number of mutations.

Next, the researchers studied the genomes of a pediatric brain cancer types by the mutated polymerase as well as inactivated repair system and found higher numbers of mutation in the exon regions of those tumors.

The study first author Joan Frigola said, "The repair mechanism ensures that mutations do not accumulate in the genome, particularly in exons."

The researchers have an insight into the mechanism that increases the efficiency of the repair machinery in exons when compared to the introns. The higher efficiency lies in exons having a very high content of H3K36me3, which enables greater recruitment of repair proteins to exons. This, in turn, makes the repair process more, efficient, noted the authors.

The repair machinery could focus only on the most critical regions of the genome. Hence the study findings should be taken while considering DNA mutation and repair mechanism, and in studies on the evolution of tumors or species, López-Bigas concluded.