August 8, 2006 — 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
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 Eric Richards, 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
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’," Richards
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 of 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."
Epigenetic mechanisms leave DNA sequence unaltered but can affect
DNA by preventing the expression of genes. Richards 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 Richards 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," Richards says.
‘Different strokes’ for rat folks
Still, recent studies in mice and rats have fueled the controversy.
Richards 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
"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,’" Richards 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. Richards 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, " Richards 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."
Source : Washington University in St. Louis