The unselfish gene
The new biology is reasserting the primacy of the whole organism - the
individual - over the behaviour of isolated genes
Johnjoe McFadden
Friday May 6, 2005
The Guardian [U.K.]
What is a gene? Scientists eager to uncover genes for heart disease,
autism, schizophrenia, homosexuality, criminality or even genius are
finding that their quarry is far more nebulous than they imagined.
Uncovering the true nature of genes has turned biology on its head and
is in danger of undermining the whole gene-hunting enterprise.
The first clues turned up in study of the cell's metabolic pathways.
These pathways are like Britain's road networks that bring in raw
materials (food) and transport them to factories (enzymes) where the
useful components (molecules) are assembled into shiny new products
(more cells). A key concept was the rate-limiting step, a metabolic
road under strict traffic control that was thought to orchestrate the
dynamics of the entire network.
Biotechnologists try to engineer cells to make products but their
efforts are often hindered, apparently by the tendency of the key
genes controlling the rate-limiting steps to reassert their own
agenda. Scientists fought back by genetically engineering these genes
to prevent them taking control. When they inserted the engineered
genes back into the cells they expected to see an increase in yields
of their products. But they were disappointed. The metabolic pathways
slipped back into making more cells, rather than more products.
Geneticists were similarly puzzled by an abundance of genes with no
apparent function. Take the prion gene. This is the normal gene that
in mad cow disease is transformed into the pathogenic brain-destroying
protein. But what does it normally do? The standard way to investigate
what a gene does is to inactivate it and see what happens. But
geneticists who inactivated the mouse's prion gene found that the
mutant mice were perfectly normal. The prion gene, like many other
genes, seems to lack a function.
But a gene without function isn't really a gene at all. By definition,
a gene has to make a difference; otherwise it is invisible to
natural selection. Genes are those units of heredity that wrinkled
Mendel's peas and are responsible for making your eyes blue, green or
brown. A century of reductionist biology has tracked them down,
through Watson and Crick's double helix, to the billions of A, T, G
and C gene letters that were spewed out of the DNA sequencers. But now
it seems that the genes, at the level of DNA, are not the same as
genes at the level of function.
The answer to these riddles is being unravelled in an entirely new way
of doing biology: systems biology. Let's return to that road network.
We may identify a particular road, say the A45, that takes goods from
Birmingham to Coventry, and call it the BtoC road, or BtoC gene.
Blocking the A45 might be expected to prevent goods from Birmingham
reaching Coventry. But of course it doesn't. because there are lots of
other ways for the goods to get through. In truth the road (or gene)
from BtoC isn't just the A45 but includes all those other routes.
Rather than having a single major function, most genes, like roads,
probably play a small part in lots of tasks within the cell. By
dissecting biology into its genetic atoms, reductionism failed to
account for these multitasking genes. So the starting point for
systems biologists isn't the gene but rather a mathematical model of
the entire cell. Instead of focusing on key control points, systems
biologists look at the system properties of the entire network. In
this new vision of biology, genes aren't discrete nuggets of genetic
information but more diffuse entities whose functional reality may be
spread across hundreds of interacting DNA segments.
This radical new gene concept has major implications for the gene
hunters. Despite decades of research few genes have been found that
play anything more than a minor role in complex traits like heart
disease, autism, schizophrenia or intelligence. The reason may be that
such genes simply don't exist. Rather than being caused by single
genes these traits may represent a network perturbation generated by
small, almost imperceptible, changes in lots of genes.
And what about selfish genes, the concept introduced by the Oxford
biologist Richard Dawkins to describe how some genes promote their own
proliferation, even at the expense of the host organism? The concept
has been hugely influential but has tended to promote a reductionist
gene-centric view of biology. This viewpoint has been fiercely
criticised by many biologists, such as the late Stephen Jay Gould, who
argued that the unit of biology is the individual not her genes.
Systems biology is reasserting the primacy of the whole organism - the
system - rather than the selfish behaviour of any of its components.
Systems biology courses are infiltrating curricula in campuses across
the globe and systems biology centres
