Featured Research

from universities, journals, and other organizations

Environmental Triggers May Promote Human Genetic Variation

Date:
May 1, 2006
Source:
Cold Spring Harbor Laboratory
Summary:
In this month's issue of the leading scientific journal Genome Research, scientists from Kyushu University report how environmentally damaged DNA may contribute to human genetic diversity. They describe the co-occurrence of an aberrant nucleobase, called 8-oxoguanine (8-oxoG), with genomic regions enriched in meiotic recombination "hotspots" and single nucleotide polymorphisms (SNPs). The findings have implications for understanding the interplay between heredity and the environment in shaping human phenotypic variation.

In this month's issue of the leading scientific journal Genome Research, scientists from Kyushu University report how environmentally damaged DNA may contribute to human genetic diversity. They describe the co-occurrence of an aberrant nucleobase, called 8-oxoguanine (8-oxoG), with genomic regions enriched in meiotic recombination "hotspots" and single nucleotide polymorphisms (SNPs). The findings have implications for understanding the interplay between heredity and the environment in shaping human phenotypic variation.

Human DNA is constantly barraged by a variety of environmental agents, including UV light and chemicals, as well as by reactive oxygen species (ROS), which are produced as byproducts of normal metabolic reactions or as molecular executors of host defense. These agents may cause the nucleobases in DNA to spontaneously undergo a chemical transformation known as oxidation. 8-oxoG is an oxidized form of the common nucleobase guanine (G), and when present in the genome, may form an unconventional base-pair with adenine (A). When DNA replication occurs, the abnormally placed adenine is paired with a thymine (T) instead of the original guanine, thereby resulting in a permanent nucleobase change.

One might intuitively expect the distribution of aberrant 8-oxoG nucleobases to be randomly distributed throughout the genome, but in their new study, Dr. Yusaku Nakabeppu and his colleagues demonstrated otherwise. Nakabeppu teamed up with Drs. Mizuki Ohno and Tomofumi Miura, among others, to investigate the distribution of 8-oxoG on spreads of normal human chromosomes with fluorescently labeled antibodies that specifically attached to 8-oxoG positions. Intriguingly, the dot-like fluorescent signals did not cover the chromosomes uniformly but rather, exhibited a striking bias for chromosomal regions that contain higher meiotic recombination rates and SNP densities. Furthermore, the distribution and intensity of 8-oxoG was remarkably similar in different individuals.

"We suggest that 8-oxoG accumulation in a particular region of a chromosome causes meiotic recombination," says Nakabeppu. "Our theory is supported by studies showing that enzymes involved in the repair of oxidative DNA damage can also induce homologous recombination. These enzymes are highly expressed in the ovary and testis, where meiotic recombination normally occurs. Furthermore, meiotic recombination rates in females are significantly higher than in males, probably because oocytes are exposed to oxidative stress for longer periods of time than are spermatocytes."

The uneven distribution of SNPs across the human genome has been documented for some time, but the causes of these nucleobase substitutions and the factors determining their distribution are largely unknown. Nakabeppu, therefore, also suggests that 8-oxoG, due to its mutagenic potential, may contribute to the formation of SNPs.

But why the clustering of 8-oxoG?

"The factors determining the distribution of 8-oxoG are still unknown," explains Nakabeppu. "One can certainly argue that there must be another factor that coincidentally increases the recombination rate or the formation of SNPs in addition to the accumulation of 8-oxoG in a particular region of the chromosome. The local structures of chromosomes and their replication or transcription might help to determine the distribution of 8-oxoG, but further analysis is required to fully understand the mechanistic relationship between 8-oxoG, recombination, and mutagenesis."

Genome Research (www.genome.org) is an international, monthly, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics.

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit www.cshlpress.com.


Story Source:

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


Cite This Page:

Cold Spring Harbor Laboratory. "Environmental Triggers May Promote Human Genetic Variation." ScienceDaily. ScienceDaily, 1 May 2006. <www.sciencedaily.com/releases/2006/04/060430225905.htm>.
Cold Spring Harbor Laboratory. (2006, May 1). Environmental Triggers May Promote Human Genetic Variation. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2006/04/060430225905.htm
Cold Spring Harbor Laboratory. "Environmental Triggers May Promote Human Genetic Variation." ScienceDaily. www.sciencedaily.com/releases/2006/04/060430225905.htm (accessed September 20, 2014).

Share This



More Health & Medicine News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
How The 'Angelina Jolie Effect' Increased Cancer Screenings

How The 'Angelina Jolie Effect' Increased Cancer Screenings

Newsy (Sep. 19, 2014) Angelina's Jolie's decision to undergo a preventative mastectomy in 2013 inspired many women to seek early screenings for the disease. Video provided by Newsy
Powered by NewsLook.com
The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. Video provided by Reuters
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:
from the past week

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