Featured Research

from universities, journals, and other organizations

DNA sequence itself influences mutation rate, new research indicates

Date:
May 24, 2010
Source:
Cold Spring Harbor Laboratory
Summary:
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 new study, researchers have identified intrinsic properties of DNA that influence mutation rate, shedding light on mechanisms involved in genome maintenance and potentially disease.

Intrinsic properties of DNA that influence mutation rate have been identified in new research.
Credit: iStockphoto/Andrew Johnson

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 in Genome Research, 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.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Walser J, Furano A. The mutational spectrum of non-CpG DNA varies with CpG content. Genome Research, 2010; DOI: 10.1101/gr.103283.109

Cite This Page:

Cold Spring Harbor Laboratory. "DNA sequence itself influences mutation rate, new research indicates." ScienceDaily. ScienceDaily, 24 May 2010. <www.sciencedaily.com/releases/2010/05/100524092348.htm>.
Cold Spring Harbor Laboratory. (2010, May 24). DNA sequence itself influences mutation rate, new research indicates. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2010/05/100524092348.htm
Cold Spring Harbor Laboratory. "DNA sequence itself influences mutation rate, new research indicates." ScienceDaily. www.sciencedaily.com/releases/2010/05/100524092348.htm (accessed October 2, 2014).

Share This



More Health & Medicine News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins