Wistar study demonstrates heritability of non-genomic information

It’s one of the defining tenets of modern biology: The characteristics of a living organism are coded into the organism’s DNA, and only information in the DNA can be passed to the organism’s offspring.

A new study by scientists at The Wistar Institute, however, suggests that this is not the full story. Instructions that control gene activity and are recorded solely in the molecular packaging of the DNA can also be passed to an organism’s progeny, according to the new data. This heritable information is distinct from the genetic information coded in the DNA and is referred to by scientists as being “epigenetic” in nature. A report on the study appears in the November 1 issue of Genes & Development.

“The implication of our findings is that, parallel to the genetic information in our DNA, we also inherit epigenetic information to ensure that the regulation of our genes is executed correctly,” says Jumin Zhou, Ph.D., an assistant professor in the gene expression and regulation program at Wistar and senior author on the new study.

In their experiments with fruit flies, Zhou and his colleagues investigated certain regulatory elements involved in controlling the homeotic gene complex, a large and complex gene region responsible for the proper development of the basic body plan. These vital genes have been highly conserved in evolution, appearing in species as divergent as fruit flies, mice, and humans. Large genes often employ highly sophisticated regulatory mechanisms: a mandatory promoter that activates transcription of the gene, enhancers that send instructions to the promoter, and specialized regulatory DNA elements such as insulators that can block or augment communication between enhancers and the promoter.

Zhou’s team studied a regulatory element called the Promoter Targeting Sequence, or PTS. They showed that the PTS overcomes an insulator to facilitate, but also restrict, the activity of distant enhancers of a single promoter. Intriguingly, however, they also found that while the PTS required the insulator to target its designated promoter, the insulator could then be removed from the system without effect: With the PTS alone, no activity was seen. With the PTS and the insulator, the PTS effectively targeted its promoter. Then, with the insulator removed, PTS continued to target its promoter.

“The insulator was required to initiate a genetic process,” Zhou says. “But then, even without the presence of the insulator, and even though no change was made to the gene, the process was self-perpetuating through multiple generations. This evidence points strongly to the fact of epigenetic inheritance.”

The notion that epigenetic alterations can be passed from generation to generation complicates the standard model of genetics. Scientists have long held the view that acquired changes in the regulatory molecules associated with DNA are removed in the germ line cells, reset to a baseline state. Based on the current study, as well as other research conducted over the last few years, this does not appear to be entirely true.

These recent observations necessarily recall the theories of 19th Century scientist Jean-Baptiste Lamarck, who postulated that traits acquired by parents during their lives could be passed on to their offspring. Lamarck’s ideas about evolutionary process were overtaken in subsequent years by those of naturalist Charles Darwin and, later, the monk Gregor Mendel. Recent advances in epigenetics, however, have begun to suggest that Lamarck may have been at least partly correct, for reasons and in ways that he could never have anticipated.

“I don’t know of any example where an acquired trait has been written into the genome, into the DNA,” says Zhou. “Still, it may be time to revisit the Lamarckian school of thought.”

The lead author on the Genes & Development study is Qing Lin, Ph.D. Additional coauthors are Qi Chen, M.D., and Lan Lin, M.S. Assistant professor Jumin Zhou, Ph.D., is the senior author. All authors are based at The Wistar Institute. Funding for the research was provided by the National Institutes of Health, the March of Dimes Birth Defects Foundation, the Edward Mallinckrodt, Jr., Foundation, and the Concern Foundation.