Environmental changes can change genes......

[Guest guest]

Twin Data Highlights Genetic Changes

By Rick Weiss

A mysterious biological mechanism that subtly changes the way people's

genes behave may account for many of the surprising differences between

identical twins, researchers announced yesterday.

Geneticists said the new work, by an international team of scientists who

studied the DNA of more than 80 twins, strengthens the case that a fledgling

research field called epigenetics holds the long-sought answer to one of

biology's toughest questions: How do environmental influences, such as

exposure to pollutants, consumption of certain foods or perhaps even

powerful emotional experiences, produce lasting and potentially

life-altering changes in a person's DNA?

Beyond its potential importance for understanding differences in identical

twins, epigenetics could explain many of the twists of fate that affect

ordinary people -- why one person may be struck by cancer, for example,

while another is spared, even though neither's DNA harbors a cancer-causing

mutation.

" This is how the environment talks to the genome, " said Rudolf Jaenisch, a

geneticist at the Whitehead Institute for Biomedical Research in Cambridge,

Mass., who was not part of the project. " This paper says lifestyle, or

environmental influences or whatever you want to call them, have a real

influence on your DNA. "

Baylin, a professor of oncology and medicine at s Hopkins

Medical Institutions in Baltimore, said the new work points to the roots of

a host of chronic diseases. " This could lead to far-reaching revelations

about how our environment breeds predispositions for lots of diseases, like

diabetes, cancer and heart disease. "

Human cells have tens of thousands of genes inside them, each with its own

job, such as producing energy or overseeing cell division. But only certain

genes are active at any given time or in any cell type while the rest are

appropriately dormant -- a grand orchestration that adds up to a

smooth-running life.

The new research, led by F. Fraga and Manel Esteller of the Spanish

National Cancer Center in Madrid, focused on two biological mechanisms that

influence gene activity. In one, called DNA methylation, enzymes inside a

cell attach a minuscule molecular decoration to a gene, deactivating that

gene. In the other, called histone acetylation, a dormant gene is made

active again.

These altered genetic settings can last a lifetime (though they are not

passed down to a person's offspring) and can be important if, say, the gene

turned off is one that protects against cancer. The extent to which

epigenetic changes are preprogrammed from birth or spurred by factors

outside the body has been unclear.

In the new work, described in today's issue of Proceedings of the National

Academy of Sciences, researchers measured the extent to which twins of

various ages, from 3 to 74, differed in the number and variety of genes that

had been either turned on or shut down by epigenetic processes. They found

that young twins had almost identical epigenetic profiles but that with age

their profiles became more and more divergent.

In a finding that scientists said was particularly groundbreaking, the

epigenetic profiles of twins who had been raised apart or had especially

different life experiences -- including nutritional habits, history of

illness, physical activity, and use of tobacco, alcohol and drugs --

differed more than those who had lived together longer or shared similar

environments and experiences.

Small epigenetic events before birth probably account for many of the minor

distinguishing differences in the appearance, personality and general health

of young twins, Estella said, and a lifetime of further epigenetic changes

gradually increases individuality.

" Both nature and nurture are acting on these twins, " Estella said.

" Epigenetics is the bridge or the interplay between them. "

Francis , director of the National Human Genome Research Institute,

said the work adds to an emerging recognition that scientists must move

beyond their long-standing focus on the inherited spelling of people's DNA

code and the occasional mutation or outright " misspelling. " Epigenetic

changes do not alter genetic spellings but may account for as many cases of

cancer and other diseases as full-blown gene mutations, he said.

" Here's something where Mendel, and Crick all seem to have missed

some crucial goodies, " said , referring to pioneers of genetic

research. 's institute, along with the National Cancer Institute and

others, intends to launch a major effort to identify the many epigenetic

changes that contribute to cancer.

Scientists want to identify the epigenetic changes wrought by specific

environmental exposures -- whether dietary factors, environmental toxins or

more nuanced influences such as persistent stress -- and develop drugs that

can reverse those alterations.

, director of the Norris Comprehensive Cancer Center at the

University of Southern California in Los Angeles, likened epigenetic

alterations to the clothes worn by genes. " The clothes are really what

determine how the genome works, " he said. " The clothes can get tattered by

these changes, which can lead to different susceptibilities to disease. "