Epigenetics: 100 Reasons To Change The Way We Think About

Genetics
ScienceDaily (May 20, 2009) — For years, genes have been considered the
one and only way biological traits could be passed down through generations
of organisms.
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Not anymore.
Increasingly, biologists are finding that non-genetic variation acquired during the life of an organism can
sometimes be passed on to offspring—a phenomenon known as epigenetic inheritance. An article
forthcoming in the July issue of The Quarterly Review of Biology lists over 100 well-documented cases of
epigenetic inheritance between generations of organisms, and suggests that non-DNA inheritance
happens much more often than scientists previously thought.
Biologists have suspected for years that some kind of epigenetic inheritance occurs at the cellular level.
The different kinds of cells in our bodies provide an example. Skin cells and brain cells have different
forms and functions, despite having exactly the same DNA. There must be mechanisms—other than DNA
—that make sure skin cells stay skin cells when they divide.
Only recently, however, have researchers begun to find molecular evidence of non-DNA inheritance
between organisms as well as between cells. The main question now is: How often does it happen?
"The analysis of these data shows that epigenetic inheritance is ubiquitous …," write Eva Jablonka and
Gal Raz, both of Tel-Aviv University in Israel. Their article outlines inherited epigenetic variation in
bacteria, protists, fungi, plants, and animals.
These findings "represent the tip of a very large iceberg," the authors say.
For example, Jablonka and Raz cite a study finding that when fruit flies are exposed to certain chemicals,
at least 13 generations of their descendants are born with bristly outgrowths on their eyes. Another study
found that exposing a pregnant rat to a chemical that alters reproductive hormones leads to generations
of sick offspring. Yet another study shows higher rates of heart disease and diabetes in the children and
grandchildren of people who were malnourished in adolescence.
In these cases, as well as the rest of the cases Jablonka and Raz cite, the source of the variation in
subsequent generations was not DNA. Rather, the new traits were carried on through epigenetic means.
There are four known mechanisms for epigenetic inheritance. According to Jablonka and Raz, the best
understood of these is "DNA methylation." Methyls, small chemical groups within cells, latch on to certain
areas along the DNA strand. The methyls serve as a kind of switch that renders genes active or inactive.
By turning genes on and off, methyls can have a profound impact on the form and function of cells and
organisms, without changing the underlying DNA. If the normal pattern of methyls is altered—by a
chemical agent, for example—that new pattern can be passed to future generations.
The result, as in the case of the pregnant rats, can be dramatic and stick around for generations, despite
the fact that underlying DNA remains unchanged.
Lamarck revisited
New evidence for epigenetic inheritance has profound implications for the study of evolution, Jablonka
and Raz say.
"Incorporating epigenetic inheritance into evolutionary theory extends the scope of evolutionary thinking
and leads to notions of heredity and evolution that incorporate development," they write.
This is a vindication of sorts for 18th century naturalist Jean Baptiste Lamarck. Lamarck, whose writings
on evolution predated Charles Darwin's, believed that evolution was driven in part by the inheritance of
acquired traits. His classic example was the giraffe. Giraffe ancestors, Lamarck surmised, reached with
their necks to munch leaves high in trees. The reaching caused their necks to become slightly longer—a
trait that was passed on to descendants. Generation after generation inherited slightly longer necks, and
the result is what we see in giraffes today.
With the advent of Mendelian genetics and the later discovery of DNA, Lamarck's ideas fell out of favor
entirely. Research on epigenetics, while yet to uncover anything as dramatic as Lamarck's giraffes, does
suggest that acquired traits can be heritable, and that Lamarck was not so wrong after all.

Epigenetics: DNA Isn’t Everything

ScienceDaily (Apr. 13, 2009) — Research into epigenetics has shown that
environmental factors affect characteristics of organisms. These changes are
sometimes passed on to the offspring. ETH professor Renato Paro does not
believe that this opposes Darwin’s theory of evolution.
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A certain laboratory strain of the fruit fly Drosophila melanogaster has white eyes. If the surrounding
temperature of the embryos, which are normally nurtured at 25 degrees Celsius, is briefly raised to 37
degrees Celsius, the flies later hatch with red eyes. If these flies are again crossed, the following
generations are partly red-eyed – without further temperature treatment – even though only white-eyed
flies are expected according to the rules of genetics.
Environment affects inheritance
Researchers in a group led by Renato Paro, professor for Biosystems at the Department of Biosystems
Science and Engineering (D-BSSE), crossed the flies for six generations. In this experiment, they were
able to prove that the temperature treatment changes the eye colour of this specific strain of fly, and that
the treated individual flies pass on the change to their offspring over several generations. However, the
DNA sequence for the gene responsible for eye colour was proven to remain the same for white-eyed
parents and red-eyed offspring.
The concept of epigenetics offers an explanation for this result. Epigenetics examines the inheritance of
characteristics that are not set out in the DNA sequence. For Paro, epigenetic mechanisms form an
additional, paramount level of information to the genetic information of DNA.
Such phenomena could only be examined in a descriptive manner in the past. Today, it has been
scientifically proven, which molecular structures are involved: important factors are the histones, a kind of
packaging material for the DNA, in order to store DNA in an ordered and space-saving way. It is now
clear that these proteins have additional roles to play. Depending on the chemical group they carry, if they
are acetylated or methylated, they permanently activate or deactivate genes. New methods now allow
researchers to sometimes directly show which genes have been activated or deactivated by the histones.
Cells have a memory
Epigenetic marks, such as the modifications of the histones, are also important for the specialisation of
the body’s cells. They are preserved during cell division and are passed on to the daughter cells. If skin
cells divide, more skin cells are created; liver cells form liver cells. In both cell types, all genes are
deactivated except the ones needed by a skin or liver cell to be a skin or liver cell, and to function
appropriately. The genetic information of the DNA is passed on along with the relevant epigenetic
information for the respective cell type.
Paro’s group is researching this cell memory. It is still unclear how the epigenetic markers are passed on
to the daughter cells. During cell division, the DNA is doubled, which requires the histones – as the
current picture suggests – to break apart. The question is therefore how cellular memory encoded by
epigenetic mechanisms survives cell division.
Emerging area of research
A similar question remains for the inheritance of the epigenetic characteristics from parents to offspring.
They now know that when the gametes are formed, certain epigenetic markers remain and are passed on
to the offspring. The questions, which are currently being researched, are how much and which part of the
epigenetic information is preserved and subsequently inherited.
The research is also looking at the influence of various substances from the environment on the
epigenetic constitution of organisms, including humans. Diet and epigenetics appear to be closely linked.
The most well known example is that of the Agouti mice: they are yellow, fat and are prone to diabetes
and cancer. If Agouti females are fed with a cocktail of vitamin B12, folic acid and cholin, directly prior to
and during pregnancy, they give birth to mainly brown, slim and healthy offspring. They in turn mainly
have offspring similar to themselves.
Contradiction to Darwin?
Environmental factors, which change the characteristics of an individual and are then passed on to its
offspring, do not really fit into Darwin’s theory of evolution. According to his theory, evolution is the result
of the population and not the single individual. “Passing on the gained characteristics fits more to
Lamarck’s theory of evolution”, says Paro.
However, he still does not believe Darwin’s theory of evolution is put into question by the evidence of
epigenetics research. “Darwin was 100 percent right”, Paro emphasises. For him, epigenetics
complement Darwin’s theory. In his view, new characteristics are generated and passed on via
epigenetics, subject to the same mechanisms of evolution as those with a purely genetic origin.

Does Environment Influence Genes? Researcher Gives Hard

Thoughts On Soft Inheritance
ScienceDaily (Aug. 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 generations.
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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 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'," 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."
Packing DNA
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 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,'" 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."