Source: Columbia
University Medical Center
Evidence from human famines and animal studies suggests that
starvation can affect the health of descendants of famished individuals. But
how such an acquired trait might be transmitted from one generation to the next
has not been clear. A new study, involving roundworms, shows that starvation
induces specific changes in so-called small RNAs and that these changes are
inherited through at least three consecutive generations, apparently without
any DNA involvement. The study, conducted by Columbia University Medical Center
(CUMC) researchers, offers intriguing new evidence that the biology of inheritance
is more complicated than previously thought. The study was published in the
July 10 online edition of the journal Cell.
The idea that acquired
traits can be inherited dates back to Jean Baptiste Larmarck (1744-1829), who
proposed that species evolve when individuals adapt to their environment and
transmit the acquired traits to their offspring. According to Lamarckian
inheritance, for example, giraffes developed elongated long necks as they
stretched to feed on the leaves of high trees, an acquired advantage that was
inherited by subsequent generations. In contrast, Charles Darwin (1809-82)
later theorized that random mutations that offer an organism a competitive
advantage drive a species' evolution. In the case of the giraffe, individuals
that happened to have slightly longer necks had a better chance of securing
food and thus were able to have more offspring. The subsequent discovery of
hereditary genetics supported Darwin's theory, and Lamarck's ideas faded into
obscurity.
"However, events like the Dutch famine of World War II have
compelled scientists to take a fresh look at acquired inheritance," said
study leader Oliver Hobert, PhD, professor of biochemistry and molecular
biophysics and a Howard Hughes Medical Institute Investigator at CUMC. Starving
women who gave birth during the famine had children who were unusually
susceptible to obesity and other metabolic disorders, as were their
grandchildren. Controlled animal experiments have found similar results,
including a study in rats demonstrating that chronic high-fat diets in fathers
result in obesity in their female offspring.
In a 2011 study, Oded Rechavi, a postdoctoral fellow in Dr.
Hobert's laboratory, found that roundworms (C. elegans) that developed
resistance to a virus were able to pass along that immunity to their progeny
for many consecutive generations. The immunity was transferred in the form of
small viral-silencing RNAs working independently of the organism's genome.
Other studies have reported similar findings, but none of these addressed
whether a biological response induced by natural circumstances, such as famine,
could be passed on to subsequent generations.
To address this question, Dr. Hobert's team starved roundworms
for six days and then examined their cells for molecular changes. The starved
roundworms, but not controls, were found to have generated a specific set of
small RNAs. (Small RNAs are involved in various aspects of gene expression but
do not code for proteins.) The small RNAs persisted for at least three
generations, even though the worms were fed normal diets. The researchers also
found that these small RNAs target genes with roles in nutrition.
Since these small RNAs are produced only in response to
starvation, they had to have been passed from one generation to another.
"We know from other studies that small RNAs can be transported from cell
to cell around the body," said Dr. Hobert. "So, it's conceivable that
the starvation-induced small RNAs found their way into the worms' germ cells --
that is, their sperm or eggs. When the worms reproduced, the small RNAs could
have been transmitted generationally in the cell body of the germ cells,
independent of the DNA."
The study also found that the progeny of the starved worms had a
longer life span than the progeny of the controls. "We have not shown that
the starvation-induced small RNAs were responsible for the increased longevity
-- it's just a correlation," said Dr. Hobert. "But it's possible that
these small RNAs provided a means for the worms to control the expression of
relevant genes in later generations."
The findings have no immediate clinical application.
"However, they do suggest that we should be aware of other things --
beyond pure DNA changes -- that may have a long-term impact on the health of an
organism," said Dr. Hobert. "In other words, something that happened
to one generation, whether famine or some other traumatic event, may be
relevant to the health of its descendants for generation.
By:
Ankita Nagpal
Faculty BII
