Epigenetics and introns: Life beyond DNA

The discovery and gradual elucidation of DNA and the genetic code over the last half century was certainly one of the most important achievements in science during that time – or arguably, any time. DNA and genetics also, rightfully, have dominated much of the thinking and interest in the biological sciences. So, without taking away anything from that scientific progress, it’s worth noting that a movement is afoot in the biological sciences that questions not so much the centrality of DNA but its dominance. In this emerging point of view, DNA still plays a central role; it is the code giver, but it exists in a more complex interactive environment where the pathways to gene expression (how the genes translate into amino acids and proteins) are actually networks involving many ‘players’ including, crucially, the many forms of RNA and the subtle effects of what used to be routinely called ‘junk DNA’ (non-coding sections of the genome known as introns).

Most people who have had at least a rudimentary exposure to biology are aware of DNA. The drama of ‘the race to discover the genetic code’ as narrated by the story of Watson and Crick has percolated a long way into the cultural psyche. What is much less known is that many geneticists, molecular biologists, and cell biologists are now heading in what appears to be an important new direction, loosely identified by the word epigenetics.

Perhaps that is as it should be, because after all, epigenetics is still a relatively raw theory, with some evidence and experimental basis, but far from proven, and even further from commanding a widespread awareness. On the other hand, because this new direction of study and experiment will have major impact on what are often identified as the ‘nature versus nurture’ issues – in short, have the potential to change how we think about the interplay of environment, life-style, and genetics – it’s important to begin the education and conversation with people outside the field of biology. That’s people like me: Writers about science; teachers of science, and of course, the broad public of people who are interested in science.

Along this line of thinking, raising awareness, here are a couple of recent items:

One comes in the form of papers and presentation by Dr. Rod Dashwood, professor of environmental and molecular toxicology at the Linus Pauling Institute at Oregon State University (USA). He views epigenetics, the study of inherited changes in gene expression caused by mechanisms other than changes in the underlying DNA, as a unifying theory in which many health problems, ranging from cancer to cardiovascular disease and neurological disorders, can all be caused at least in part by altered “histone modifications” and their effects on the reading and transcription of DNA.

His interest is in histone deacetylases (HDACs), which are enzymes that act on the amino acid lysine found on histones (proteins found in the nucleus of cells that package and order the DNA into nucleosomes). This involves the shape taken by DNA, especially during the process of reproduction (mitosis) and affects how the genes are regulated. This all sounds rather technical, and is, but it also provides insight into the subtleties of how DNA (as present in the chromosomes) interacts with its environment in the cell nucleus. In particular, Dr. Dashwood has researched the way histone deacetylases affect how DNA is packaged, which when it goes wrong, is linked to certain kinds of cancer.

The possibility of such links was unknown to scientists even ten years ago. In the case of cancer, the HDAC enzyme can prevent the expression of genes that normally suppress uncontrolled cell growth (that is, tumor growth). This happens without any mutation or error in the underlying DNA. The presence of too much HDAC in the nucleus is therefore a possible cause of cancer. However, HDAC itself can be inhibited by other compounds found in common foods: sulforaphane in broccoli, organosulfur in vegetables like onions and garlic, and butyrate, which produced in the intestine while fermenting dietary fiber. This last one, butyrate, may explain why eating more fiber might help prevent cancer.

“Metabolism seems to be a key factor, too, generating the active HDAC inhibitor at the site of action,” Dashwood said. “In cancer cells, tumor suppressors such as p21 and p53 often become epigenetically silenced. HDAC inhibitors can help turn them on again, and trick the cancer cell into committing suicide via apoptosis.

“We already know some of the things people can do to help prevent cancer with certain dietary or lifestyle approaches,” Dashwood said. “Now we’re hoping to more fully understand the molecular processes going on, including at the epigenetic level. This should open the door for new approaches to disease prevention or treatment through diet, as well as in complementing conventional drug therapies.”

[Source: EurekAlert]

The other item is an article in Cosmos Magazine titled “The trouble with genes”, written by Elizabeth Finkel. It’s by no means the only article about recent trends in genetics to point out the shifts in thinking about ‘junk DNA’ and the study of epigenetics, but it’s a good primer on the subject.

Her coverage begins with the question many biologists are asking: How is it that very complex, highly evolved, and large creatures (like man) have no more genes in their DNA than simple worms? The answer that comes back in several forms is that genes aren’t everything. Their expression – how the genes interact with the mechanisms that eventually produce the protein coded by the genes – is at least as important, especially for the development of those very complexities that distinguish man from worm.

The key to this are the many forms of RNA (ribonucleic acid), known to most people as the messenger of DNA coding. It’s turning out that its role is much more interactive, particularly in relation to the many portions of DNA that are non-coding, the so-called junk DNA.

Most of our DNA may well have originated as ‘junk’ but that junk has been put to work. One of its most common jobs is to produce tiny bits of RNA known as ‘microRNA’ that targets other RNA for destruction. MicroRNA has been shown to shut down the activity of protein-coding RNA in everything from petunias to people.

Junk DNA also plays another crucial function: it guards the DNA code from invasion by retroviruses or so-called jumping genes, which can hop about in the genome causing dangerous mutations.

Junk DNA is itself largely composed of former interlopers but, like a patriotic immigrant, it does its best to prevent any further invasions.

The RNA transcripts that run off junk DNA are still a close match to live viruses or active jumping genes, and if these junk transcripts meet up with their relatives, they inactivate them.

[Source: Cosmos Magazine ]

Her account covers some of the history of this research and is particularly good at providing examples from specific scientists. Some of this work is controversial, which the article does not explore, but it’s a good introduction in not-too-technical terms to what may someday become mainstream knowledge in genetics and molecular biology.

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