The Record 2009 - Keble College - University of Oxford

Keble College: The Record 2009
have had its anatomy and development described in complete
cellular detail. Its genome is only one thirtieth the size of the
human genome and was completely sequenced ten years ago,
partly as a pilot for the subsequent and much larger human
genome project. Now we would like to know what all its genes
are doing. But there is a surprise here: the worm has far more
genes than seem necessary to create and sustain such a simple
creature. In fact, C. elegans has over 20,000 genes, almost as
many as the 25,000 currently estimated as the number of
human genes. What are they all doing? We can begin to answer
this question by making use of an extraordinary effect called
RNA interference (RNAi for short) which was first discovered
in C. elegans and then found to be universal among plants and
animals. RNAi provides a convenient means of reducing the
activity of any chosen gene in an organism. It is ridiculously
easy to implement in C. elegans, and the method has allowed
several research teams to examine the effect of inhibiting, one
by one, most of the 20,000 genes. Sometimes this inhibition
results in death, sterility or deranged development, if the gene
is important enough, but most of the time nothing happens.
Yet evolution has preserved these apparently useless genes.
We know this, because we can almost always find exactly
the same gene in related species of nematode, which diverged
from C. elegans many millions of years ago. Genes that aren’t
useful get rapidly lost, over such periods of evolutionary
time. So it is likely that the superficially non-functional genes
are actually very important in the real life of the worm, out
there in the complex soil ecosystem that it naturally inhabits.
This is of course a much more challenging environment than
a comfortable Petri dish. Indeed, when we repeat the RNAi
experiments on certain genes, but add in pathogenic bacteria
at the same time, we find that some of the genes that are
dispensable for life in a protected environment are actually
necessary to provide defence against the pathogen.
Those are genes that are specialized for defence, but some
of the other genes we study turn out to have roles both in
immunity and in developmental processes. One of the pleasures
of pursuing research is how often the investigation of one
problem gives rise unexpectedly to an insight in a different area,
and this has happened repeatedly during our investigations
of worm immunity. Immunity and development seem to be
strongly interwoven. These crossovers also lead us to look at the
organism in a more holistic way than we used to. Fortunately
so much is known about the molecular and cellular biology
of C. elegans that it is becoming increasingly possible to view it
holistically, rather than as a collection of many different parts
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