2018/03/24

The obvious link between epigenetic factors and genetic mutations

Due to rapid genetic degradation scientists try to repair human DNA

https://www.sciencenews.org/article/new-crispr-gene-editors-can-fix-rna-and-dna-one-typo-time


Excerpt: "The new editors allow researchers to rewrite all four bases that store information in DNA and RNA. Those four bases are adenine (A) which pairs with thymine (T) (or uracil (U) in RNA), and guanine (G) pairs with cytosine (C). Mutations that change C-G base pairs to T-A pairs happen 100 to 500 times every day in human cells. Most of those mutations are probably benign, but some may alter a protein’s structure and function, or interfere with gene activity, leading to disease. About half of the 32,000 mutations associated with human genetic diseases are this type of C-G to T-A change, says Liu, a Howard Hughes Medical Institute investigator at Harvard University. Until now, there was little anyone could do about it, he says."


http://www.els.net/WileyCDA/ElsArticle/refId-a0006159.html

Excerpt: "Single‐gene and genome sequencing studies have identified base substitution mutations as a causative mechanism in human genetic diseases and cancer. These mutations do not occur randomly but are often enriched at specific DNA (deoxyribonucleic acid) sequences. The genome of most human cells contains about 50 million 5‐methylcytosine bases, the majority of them occurring at the CpG dinucleotide sequence. Methylated CpG dinucleotides are the targets of many of the mutations, mostly transition mutations (C→T or G→A), found in genetic disorders and in malignant tumours. The mechanisms that increase mutations at CpG sites include spontaneous deamination of 5‐methylcytosine and preferential interaction of such sequences with physical or chemical carcinogens. As a consequence of enhanced mutagenesis at methylated CpGs, the CpG frequency in mammalian genomes has been strongly depleted over evolutionary time."


Key Concepts


  • Methylated CpG sequences are preferentially mutated.
  • Deamination of 5‐methylcytosine leads to transition mutations at CpGs.
  • Exogenous carcinogens target methylated CpGs.
  • CpG mutations are frequent in genetic diseases and cancer.
  • DNA repair may be affected by methylation of CpG sequences.

My comment: Deamination of 5-methylcytosine is often caused by oxidative stress (keywords: deamination oxidative stress). Oxidative stress is typically result of weak nutrition (or overnutrition), lack of exercise, mental stress, bad life habits (alcohol consumption or smoking) etc.

This is why DNA sequences (also called genes) are driven by lifestyle. Any change in organisms is based on epigenetic regulation of existing biological information or gradual but inevitable corruption of information. That's why there's no mechanism for evolution. Don't get lost.