Advances in biology are often the result of discovery of important new molecules; this is partly why the field of molecular biology has come to dominate biological and medical research. In the mid 1990s some puzzling results from genetics research led to the discovery of a new class of molecules; previously unknown forms of ribonucleic acid (RNA) found in sperm. For more than half a century RNA has been known as a principal part of the cellular mechanism through which genes work by producing proteins. RNA is a polymer very similar to DNA, but differs in a subtle chemical way that results in its having quite different structures. Importantly, it can occur in a variety of two and three dimensional forms. Three of these form key components of protein production machinery: messenger RNA that carries coded information about a protein’s sequential chemical structure from the gene to the cell’s protein assembly site; ribosomal RNA that forms a kind of jig on which the assembly takes place; and transfer RNA which is an adaptor that translates genetic code and uses that information to direct the assembly of strings of the amino acid molecules which constitute proteins.
Image credit: Rfam database, Public domain, via Wikimedia Commons
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What happened in the 1990s was the surprising discovery that biologically important forms of RNA molecules are not limited to these three, but also include a set of molecular types generally called non-coding RNA (ncRNA). (Transfer RNA and ribosomal RNA are non-coding RNA molecules so, strictly speaking, these recently discovered molecules have extended an existing classification of RNA.) Amongst ncRNAs are several involved in the control of many cellular processes, mainly via participation in gene expression control (note that they were discovered in sperm, but are also found and are operational elsewhere). Some characteristics of ncRNAs are of particular interest in the context of adaptation. First, their location in sperm extends the nature and amount of information that sperm can carry from one generation to the next. Second, ncRNAs carry information and instructions between different cells and tissues. They do this by being mobile, travelling between different locations in animal bodies in blood and other body fluids. That mobility often involves small carrier structures called extracellular vesicles, and in some cases ncRNAs being transported as molecules dissolved in body fluid. These characteristics enable an epigenetic process that may prove to be an important route through which environmental conditions can influence evolution.
Extracellular vesicles and ncRNAs, then, are intercellular communication agents; they carry epigenetic information between different cells, and that, of course, is the very characteristic sought in identifying the blood soluble factor acting as the messenger in the liver wounding example. To date, there is no report demonstrating that extracellular vesicles and ncRNAs are the agents that act in this particular case, but other lines of research strongly suggest that they do transfer epigenetically heritable information from soma to germline. For example, in one study22, human tumour cells were grafted into mice. Those tumour cells had been modified to carry a gene foreign to both humans and mice, in order to make the tumour cells produce an RNA that would not normally be present in the mice and was easy to detect experimentally. Experiments showed that the tumour cells released extracellular vesicles containing the foreign RNA into the mice’s blood. Furthermore, the foreign RNA was also found in the mice’s sperm. (The researchers went to great lengths to ensure that the foreign RNA they detected was not present as the result of contamination or other trivial events.) These experiments are impressive and persuasive. The clever experimental design has demonstrated quite securely the transfer of RNA from soma to sperm because in this case the soma was the only possible source of the foreign RNAs; they simply could not have come from anywhere else.
Image credit: Charles Darwin, Public domain, via Wikimedia Commons
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The question that follows is whether RNAs being transferred from soma to sperm are biologically active and, critically important, whether their effects are evolutionarily significant.
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