A tiny worm could hold the key to understanding our own biology, writesDick Ahlstrom
A round worm the size of a grain of sand is fast becoming a hero in the annals of human biology. It is teaching us a great deal about human biology and the influence of individual proteins on the way we develop and grow.
The worm in question is Caenorhabditis elegans, which has served as a key genetic model for some years. It is important because more than half of its genes have duplicates in the human genome, and as a result, it expresses a huge number of matching proteins.
How can a worm serve as a useful model for human physiology, many would ask. The answer lies in the surprising level of gene conservation found in nature. As evolution proceeded from the earliest bacteria three to four billion years ago, any genes that provided an advantage to survival were retained in the genome. Genes in unsuccessful organisms simply died out.
Over time, a huge collection of useful genes evolved and as organisms diverged and evolution proceeded many were conserved, nature in effect avoiding the need to reinvent the biological wheel time after time.
The high level of conservation was exposed with the release of the human genome, our genetic blueprint, particularly when matched against the genomes of other species as they become available.
C elegans was the first animal to have its genome sequenced and has a predicted 19,757 genes. Almost 10,000 of these have a match in the human genetic sequence, so understanding what they do for the worm may help us understand what they do in the human body.
Separate research teams in the UK and in the US have provided two powerful examples of how this works. Both reports and an accompanying overview by a third author are published this morning in the journal, Nature.
Knowing that the genes are there and what proteins they produce isn't enough in itself, explains Dr Thomas Tuschl of Rockefeller University, New York, in an assessment of the research. "A list won't tell you what these proteins do," he writes. "One way of starting to find out is to inactivate the genes, one at a time, and see what happens."
This in fact is what the UK team, led by Dr Julie Ahringer of the Wellcome Trust/Cancer Research UK Institute and the University of Cambridge and colleagues, and the US team led by Dr Garry Ruvkun of Massachusetts General Hospital and Harvard Medical School, Boston and colleagues, have done.
"The analysis of gene function in animals and plants was revolutionised in 1998 by the discovery of the mechanism underlying 'RNA-mediated interference' (RNAi) in C elegans," writes Tuschl.
RNAi is a natural cellular defence process that protects against invading bacteria and viruses by blocking the action of targeted genes. Researchers were able to exploit this, using genetically engineered bacteria that produced specific RNA forms as a way to selectively switch off certain genes.
C elegans helps this process because of its eating habits, explains Tuschl. "C elegans is remarkable in that such 'gene silencing' can result when the RNA has simply been eaten." The worm's preferred diet is the bacterium Escherichia coli and E coli is an old friend of microbiologists. Engineered E coli is fed to the worm and targeted genes can be silenced.
The UK team produced a library of more than 16,000 bacteria expressing the appropriate RNA and used them to switch off specific genes. The bacteria were fed to the worms and the effect of silencing a particular gene could be gauged.
The US group used an RNA interference library to investigate a particular biological pathway, that related to the regulation of fat storage in C elegans. Their systematic survey found 305 genes linked to the reduction of body fat and 112 genes that increased fat storage.
In this way, research on a worm is providing insights into human physiology. Knowing what a gene and its protein does is central to developing new therapies for the treatment of human disorders.
For example, the US team believes that many of the genes it identified and the proteins they produce are good candidates for drug development.