Navigation Links
New research indicates that DNA sequence itself influences mutation rate
Date:5/24/2010

May 24, 2010 Genetic variation due to DNA mutation is a driving force of adaptation and evolution, as well as a contributing factor to disease. However, the mechanisms governing DNA mutation rate are not well understood. In a report published online today in Genome Research (http://www.genome.org), researchers have identified intrinsic properties of DNA that influence mutation rate, shedding light on mechanisms involved in genome maintenance and potentially disease.

Some DNA mutations are subject to natural selection, either conferring a biological advantage that is selected for, or a negative effect that is selected against. Mutations not under selection are said to be neutral, and the rate at which neutral mutations accumulate is reflective of the true DNA mutation rate. Researchers can estimate this mutation rate by comparing neutrally evolving sequences in species that share a common ancestor.

Interestingly, the neutral mutation rate can vary significantly between different regions of chromosomes. This suggests that the context of the DNA influences how rapidly it accumulates mutations. Sequence high in pairs of the bases C and G (CpGs) where the C's are chemically modified, have been positively correlated with mutation rate. However, the chemical modification of CpGs makes them prone to mutation themselves, and with time they are eliminated from neutrally evolving sequences. NIH researchers Jean-Claude Walser and Anthony Furano have taken advantage of this property to investigate the role of CpGs on the mutation rate of non-CpG DNA, by comparing "old" and "young" sequences.

Walser and Furano compared the CpG content and DNA changes in inactive L1 retrotransposons shared by humans and chimpanzees. These ancient DNA sequences that had previously expanded in our common ancestor to multiple copies interspersed throughout the genome, but are now extinct "DNA fossils" that are neutrally evolving.

The researchers had previously noted that the older L1s have a lower CpG content than the younger sequences as expected, but here they observed two particularly striking features: "The overall mutation rate in the older fossil sequences dropped dramatically," said Furano, indicating a certain CpG content threshold is required to affect the non-CpG mutation rate. "And most provocatively, the types of mutations changed significantly."

This means that CpGs are not only promoting mutations, but they are also influencing how the non-CpG sequences around them are being mutated, an extension of what the authors call the "CpG effect." These findings strongly support the hypothesis that the co-variation of CpG content and non-CpG mutation rate is a property of the DNA sequence itself, and not a result of the chromosomal location.

"Intriguingly, the CpG effect revealed by our studies mimics the altered mutational state that has been demonstrated for certain cancers," Furano noted. Furthermore, the authors expect that this work will open the door to future studies investigating the mechanisms by which CpGs exert their influence on mutation rate and how this is involved in the critical process of genome maintenance. Scientists from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) contributed to this study.


'/>"/>

Contact: Peggy Calicchia
calicchi@cshl.edu
516-422-4012
Cold Spring Harbor Laboratory
Source:Eurekalert

Related medicine news :

1. New research identifies modifiable risk factors for heart disease
2. Nuvo Research announces early redemption of 5% convertible debentures
3. Researcher to track spread of disease, malware and power outages
4. UCSF Researchers Identify Regulator of Human Sperm Cells
5. Octapharma Accepting Applications for Research Grants Through March 31
6. Valentine Tailgate Party for the Girls with Festive Ideas from Beauty Research
7. New Research Shows Genes of Pregnant Women and Their Fetuses Can Increase the Risk of Preterm Labor
8. University of Maryland chemist receives Astellas Award for blindness prevention research
9. Developing a cyberinfrastructure for comparative effectiveness in cancer research
10. Women should be allowed to eat, drink during labor: Queens University researcher
11. Parkinsons disease research uncovers social barrier
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2017)... ... June 27, 2017 , ... Hammer Strength, the world’s leading performance strength ... Gillett of the Houston Rockets the NBSCA Strength & Conditioning Coach of the Year. ... NBSCA members who vote to select the coach who embodies the highest level of ...
(Date:6/26/2017)... ... June 26, 2017 , ... Torrance dentist, Dr. Robert Mondavi DDS , ... most noticeable aspects of a person’s appearance. A healthy, radiant smile can make a ... balanced teeth, everyone can have the smile of their dreams with cosmetic dentistry. , ...
(Date:6/26/2017)... ... June 26, 2017 , ... ... is revolutionizing the way women look and feel about themselves and their sexual ... female sexual dysfunction and urinary leakage head on with a ground breaking medical ...
(Date:6/25/2017)... (PRWEB) , ... June 25, 2017 , ... FCPX LUT ... into an old-fashioned vintage look. FCPX LUT Vintage Volume 2 contains 60 different color-grade ... grain for distorted looks, vignettes and blurs to single out subjects, plus much more. ...
(Date:6/25/2017)... ... ... currently bearing down on Northern California pushing temperatures to the maximum, many people are heading ... laser hair removal. , The process of summer waxing and constantly shaving unwanted hair, ... to do is get out, dive in and cool off. There is a way to ...
Breaking Medicine News(10 mins):
(Date:6/8/2017)... Fla. , June 8, 2017  Less than ... that hit more than 200,000 companies, including hospital networks, ... being heralded as one of the largest online extortion ... in the healthcare market, it is imperative that providers ... protect their data from this — and many other ...
(Date:6/7/2017)... , June 6, 2017  Diplomat Specialty Infusion Group, a brand ... environment to its Iowa location. ... now features an ISO 7 cleanroom—the standard needed to ... with a low level of pollutants. ... nutrition consumers and better serve our Iowa ...
(Date:6/1/2017)... Nutriceutical Holdings (NH), parent company of Physician ... KD Pharma Group have decided to join forces through ... Group. KD Pharma Group will become the largest shareholder ... entire company. "We believe we have found ... growing the NH companies by providing us with supply ...
Breaking Medicine Technology: