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In 1944, the Nazis caused widespread famine in Western Netherlands after they blocked food supplies. A group of pregnant women living in the Netherlands, laboring under starvation conditions imposed by a harsh winter and food embargo, gave birth to relatively small babies. When their children grew up, in relative prosperity, to have children of their own their babies were unexpectedly small. This was the birth place of epigenetics – the study of genetic changes sparked by external factors that become passed down to subsequent generations. A new study may have discovered an underlying mechanism that transfers the starvation response to future generations after they studied food-deprived worms.

The famine that lingers

“There are possibly several different genetic mechanisms that enable inheritance of traits in response to changes in the environment. This is a new field, so these mechanisms are only now being discovered,” said Dr. Oded Rechavi of Tel Aviv University’s Faculty of Life Sciences and Sagol School of Neuroscience. “We identified a mechanism called ‘small RNA inheritance’ that enables worms to pass on the memory of starvation to multiple generations.”

RNA (ribonucleic acid) molecules differ from DNA molecules in several ways. RNA molecules are single-stranded, and their nucleotides contain ribose rather than deoxyribose sugar. Like DNA, RNA nucleotides each contain one of four organic bases, but whereas adenine, cytosine, and guanine nucleotides occur in both DNA and RNA, thymine nucleotides are found only in DNA. In place of thymine nucleotides, RNA molecules contain uracil nucleotides. A type of RNA, messenger RNA molecules (mRNA) instructs the production of certain proteins that allow cells to function properly. Basically, all RNA molecules have a regulatory function with different types of RNA being involved in different types of regulatory activity. Small RNAs are maybe the most intriguing – short molecules, hence the name, that regulates gene expression by shutting them on or off.

Dr. Rechavi first became interested in studying starvation-induced epigenetic responses following a discovery made as a post-doctorate in Prof. Hobert’s lab at Columbia University Medical Center in New York. “Back then, we found that small RNAs were inherited and that this inheritance affected antiviral immunity in worms. It was obvious that this was only the tip of the iceberg,” he said.

The researchers grew common worms (C.elegans nematodes) in a food-deprived environment and followed their genetic markup. They noticed the starved worms  responded by producing small RNAs, which function by regulating genes through a process that is known as RNA interference (RNAi). The researchers discovered that the starvation-responsive small RNAs target genes that are involved in nutrition and that these became inherited by at least three subsequent generations of worm specimens.

“We were also surprised to find that the great-grandchildren of the starved worms had an extended life span,” said Dr. Rechavi. “To the best of our knowledge, our paper provides the first concrete evidence that it’s enough to simply experience a particular environment — in this case, an environment without food — for small RNA inheritance and RNA interference to ensue. In this case, the environmental challenge is starvation, a very physiologically relevant challenge, and it is likely that other environments induce transgenerational inheritance of small RNAs as well.

“We identified genes that are essential for production and for the inheritance of starvation-responsive small RNAs. RNA inheritance could prove to be an important genetic mechanism in other organisms, including humans, acting parallel to DNA. This could possibly allow parents to prepare their progeny for hardships similar to the ones that they experience,” Dr. Rechavi said.

There are many reasons why this research is really important. It shows yet again how important external factors are to develop and how quickly responses to significant changes or events in our lives are passed on to offspring. For instance, we know that fear and trauma are transmitted to our children and children’s children – even sexual promiscuity.

The findings were reported in the journal Cell.