The Epigenetics Revolution

We’ve known for many years that there are some other classes of RNA in our cells, specifically molecules called transfer RNA (tRNA) and ribosomal RNA (rRNA). tRNAs are small RNA molecules that can hold a specific amino acid at one end. When an mRNA molecule is read to form a protein, a tRNA carries its amino acid to the correct place on the growing protein chain. This takes place at large structures in the cytoplasm of a cell called ribosomes. The ribosomal RNA is a major component of ribosomes, where it acts like a giant scaffold to hold various other RNA and protein molecules in position. The world of RNA therefore seemed quite straightforward. There were structural RNAs (the tRNA and rRNA) and there was messenger RNA.

For decades, the stars of the molecular biology catwalk were DNA (the underlying code) and proteins (the functional, can-do molecules of the cell). RNA was relegated to being a relatively uninteresting intermediate molecule, carrying information from a blueprint to the workers on the factory floor.

Everyone working in molecular biology accepts that proteins are immensely important. They carry out a huge range of functions that enable life to happen. Therefore, the genes that encode proteins are also incredibly important. Even small changes to these protein-coding genes can result in devastating effects, such as the mutations that cause haemophilia or cystic fibrosis.

But this world view has potentially left the scientific community a bit blinkered. The fact that proteins, and therefore by extension protein-coding genes, are vitally important should not imply that everything else in the genome is unimportant. Yet this is the theoretical construct that has applied for decades now. That’s actually quite odd, because we’ve had access for many years to data that show that proteins can’t be the whole story.

Why we don’t throw away our junk

Scientists have recognised for some time that the blueprint is edited by cells before it is delivered to the workers. This is because of introns, which we met in Chapter 3. They are the sequences that are copied from DNA into mRNA, but then spliced out before the message is translated into a protein sequence by the ribosomes. Introns were first identified in 1975[123] and the Nobel Prize for their discovery was awarded to Richard Roberts and Phillip Sharp in 1993.

Back in the 1970s scientists compared simple one-celled organisms and complex creatures like humans. The amount of DNA in their cells seemed surprisingly similar, considering how dissimilar the organisms were. This suggested that some genomes must contain a lot of DNA that isn’t really used for anything, and led to the concept of ‘junk DNA’[124] – chromosome sequences that don’t do anything useful, because they don’t code for proteins. At around the same time a number of labs showed that large amounts of the mammalian genome contain DNA sequences that seem to be repeated over and over again, and don’t code for proteins (repetitive DNA). Because they don’t code for protein, it was assumed they weren’t contributing anything to the cell’s functions. They just appeared to be along for the ride[125][126]. Francis Crick and others coined the phrase ‘selfish DNA’ to describe these regions. These two models, of junk DNA and selfish DNA, have been delightfully described recently as ‘the emerging view of the genome as being largely populated by genetic hobos and evolutionary debris[127]’.

We humans are remarkable, with our trillions of cells, our hundreds of cell types, our multitudes of tissues and organs. Let’s compare ourselves (a little smugly, perhaps) with a distant relative, a microscopic worm, the nematode Caenorhabditis elegans. C. elegans, as we usually call it, is only about one millimetre long and lives in soil. It has many of the same organs as higher animals, such as a gut, mouth and gonads. However, it only consists of around 1,000 cells. Remarkably, as C. elegans develops, scientists have been able to identify exactly how each of these cells arises.

This tiny worm is a powerful experimental tool, because it provides a roadmap for cell and tissue development. Scientists are able to alter expression of a gene and then plot out with great precision the effects of that mutated gene on normal development. In fact, C. elegans has laid the foundation for so many breakthroughs in developmental biology that in 2002 the Nobel Committee awarded the Prize in Physiology or Medicine to Sydney Brenner, Robert Horvitz and John Sulston for their work on this organism.