Researcher Gives Hard Thoughts On Soft Inheritance: Above And Beyond The Gene

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Researcher Gives Hard Thoughts On Soft Inheritance: Above And Beyond

The Gene

http://www.medicalnewstoday.com/medicalnews.php?newsid=49112

Organisms, including humans, all inherit DNA from generation to

generation, what biologists call hard inheritance because the

nucleotide sequence of DNA is constant and only changes by rare

random mutation as it is passed down the generations.

But there also is evidence, especially in plants, that non-genetic

factors modifying the DNA can also be inherited. The modifications of

the genetic material take the form of small chemical additions to one

of the DNA bases and the alternative packaging of the DNA. These so-

called epigenetic modifications are known to be important for turning

genes on and off during the course of an organism's life, but their

importance in controlling inheritance has been debated. Many

biologists are skeptical of any form of soft inheritance, where the

genetic material is not constant, believing that it is only genetic

information - DNA -- that can be passed onto generations.

Now s, Ph.D., professor of biology at Washington

University in St. Louis, writing in the May issue of Nature Reviews

Genetics, analyzes recent and past research in epigenetics and the

history of evolution and proposes that epigenetics should be

considered a form of soft inheritance, citing examples in both the

plant and mammalian kingdoms.

In doing so, he evokes the pre-Darwinian evolutionist Jean-Baptiste

Lamarck (1744-1829), a name that evolutionary biologists thought long

ago left the stage, and .Soviet agronomist T.D. Lysenko. Lamarck, and

more recent neo-Lamarckian researchers, believed that the environment

plays a key role in a species acquiring inherited characteristics

that drive variation and evolution. Lamarck, for instance, believed

that shore birds acquired their long legs by constantly stretching

their legs to lift themselves out of the water and that generations

later that kind of environment gave rise to birds with long legs. Neo-

Lamarckian views of evolutionary change stress the importance of the

environment in altering inheritance.

" When most biologists hear the name Lamarck or the term soft

inheritance, the reaction is, 'Oh my God, here we go again', "

s says. " But from a molecular biology point of view there is a

mechanism to do soft inheritance, and epigenetic inheritance can be

construed as a form soft inheritance. That's all I'm saying. The

really heretical thing to say is that the environment could be

pushing the epigenetic information in a direction that is beneficial.

This is the more extreme variation of soft inheritance that raises

the hackles. "

Packing DNA

Epigenetic mechanisms leave DNA sequence unaltered but can affect DNA

by preventing the expression of genes. s cites a study that

shows certain epigenetic alleles can be inherited that affect tumor

suppressor genes. His own work in plants has often shown epigenetic

information can be inherited. The s lab specializes in

epigenetics, a biological field that deals with information

stored " above and beyond the gene, " referring to the Greek meaning of

the term. A classic epigenetic mechanism is a process known as DNA

methylation, a chemical modification of cytosine, one of the four

chemical subunits of DNA. Without proper DNA methylation, higher

organisms from plants to humans have a host of developmental

problems, from dwarfing in plants to certain death in mice.

The next level of gene regulation studied in epigenetics is DNA

packaging. DNA is wrapped around proteins similar to the way that

thread is wrapped around a spool. Loosely wrapped DNA is more readily

accessible and therefore more easily expressed than tightly wrapped

DNA, allowing another mechanism for regulation of gene expression.

The location of DNA within the nucleus also influences gene

expression.

" Epigenetics as soft inheritance in mammals puts us on a slippery

slope that many people don't want to visit, " s says.

Nutritional epigenomics

Still, recent studies in mice and rats have fueled the controversy.

s cited " a whole new world called nutritional epigenomics, "

where researchers are trying to influence epigenetic information by

of all things diet. In a study with mice hybrids, researchers

provided pregnant moms with varying levels of folate and B vitamins,

to affect DNA methylation.

" The idea was : If you pump these pregnant moms up with these dietary

supplements, you might be able to skew the DNA methylation patterns,

and thus skew the way the mice come out at the end of the day, and it

works,' " s says. " In this particular instance that says what

you're getting fed in the womb influences your phenotype - physical

and physiological attributes. "

Another study showed that early grooming and nurturing of rat pups by

rat moms affects methylation of a glucocorticoid receptor gene in the

hippocampus in the brain. If the pups get lots of nurturing the

glucocorticoid gene gets turned on and expressed early at a critical

period, providing pups the beneficial outcome to handle stress later

in life. Not enough nurturing and grooming, and the gene never gets

turned on. s says that whole mechanism appears to be the

result of changes in DNA methylation associated with changes in DNA

packaging.

" These studies do not demonstrate inheritance between generations,

but they do show that the early nutritional environment in the mice

and early behavioral environment in the rat studies can change the

DNA packaging on the genome, and that that is 'remembered' in the

cell divisions that make the rest of the organism, " s

says. " But this is not from one generation to another. No one has

shown that yet.

" To get to the issue of the more extreme variations of soft

inheritance, it has to be determined whether the environment can

induce an epigenetic change in an organism that can be inherited in

subsequent generations. Certainly, nobody has shown that an

epigenetically induced beneficial or adaptive change has been

inherited. Mechanistically, there is no reason to discount epigenetic

inheritance. The biochemical nuts and bolts are there to support it.

The big questions to resolve are how many epigenetic changes are

induced by the environment, what types of phenotypes result from

these changes, and how many of these epigenetic changes are

inherited. "