Subscribe free to our newsletters via your
. Earth Science News .

Subscribe free to our newsletters via your

Environmental Triggers May Promote Human Genetic Variation

Human DNA is constantly barraged by a variety of environmental agents.
by Staff Writers
Fukuoka, Japan (SPX) May 02, 2006
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."

Related Links
Cold Spring Harbor Laboratory

The Greenbeards Have Blue Throats In The Evolution Of Altruistic Behavior
Santa Cruz CA (SPX) May 02, 2006
A new study of side-blotched lizards in California has revealed the genetic underpinnings of altruistic behavior in this common lizard species, providing new insights into the long-standing puzzle of how cooperation and altruism can evolve.

  • Indians At Risk In Afghanistan
  • Pacific Tsunami Alert System Tests To Start Mid-May
  • Bush Contributed To Extent Of Katrina Aftermath Says Senator Lieberman
  • Humanitarian Aid Readied For Russian Quake Region

  • After A Soaring Takeoff, The Kyoto Carbon Market Slams Into Turbulence
  • CryoSat-2 To Receive Ice-Bound Research Support
  • 10 States Sue US To Regulate Greenhouse Gases
  • Canada To Adopt US Climate Change Policies

  • China Successfully Launches Remote Sensing Satellite
  • Geoinformation From Space Sharpens Population Density Maps
  • Israeli EO Bird EROS-B Safely In Orbit
  • SAIC Acquires Geo-Spatial Technologies

  • Oil prices near 74 dollars on Bolivia, Iran fears
  • UN Meeting Focuses On Long-Term Energy Solutions
  • Researchers Focus On Spacecraft Power Storage
  • Chinese Oil Safari Hits Nigeria

  • AIDS Cocktail Could Be Soon Down To Just One Pill
  • China Reports 18th Human Case Of Bird Flu
  • A Research Revolution Helping To Cure More Diseases
  • World Bank Steps Up Malaria-Control Effort

  • Environmental Triggers May Promote Human Genetic Variation
  • Protowings May Have Helped Bird Ancestors Cover Rough Terrain
  • The Greenbeards Have Blue Throats In The Evolution Of Altruistic Behavior
  • 'Uniquely Human' Component Of Language Found In Gregarious Birds

  • Pollution Slowly Choking North China's Largest Lake To Death
  • 50 Years On, Echoes Of Tragic Past Haunt Japan's Minamata City
  • Pollution In Far East Russian River 30 Times Above Norm
  • A Radioactive Wildlife Reserve In Chernobyl's No-Go Zone

  • Ancient Volcano, Seeds And Tree Rings Rewrite Late Bronze 'Med' History
  • What Is The Sound Of One Person Talking
  • Brain Power Packs In The Floating-Point Operations
  • Kennewick Man Skeletal Find May Revolutionalize Americas History

  • The content herein, unless otherwise known to be public domain, are Copyright 1995-2006 - SpaceDaily.AFP and UPI Wire Stories are copyright Agence France-Presse and United Press International. ESA PortalReports are copyright European Space Agency. All NASA sourced material is public domain. Additionalcopyrights may apply in whole or part to other bona fide parties. Advertising does not imply endorsement,agreement or approval of any opinions, statements or information provided by SpaceDaily on any Web page published or hosted by SpaceDaily. Privacy Statement