A University of Rochester professor has found strong evidence that mutations in bacteria occur more often when they are useful than when they are neutral. The finding strikes at the widely held biological principle that mutations arise randomly and without respect to their usefulness, a belief that is critical to our understanding of how life evolves. The paper by Biology Professor Barry G. Hall will appear in the September issue of the journal Genetics.
"Some mutations happen more often when they are useful than when they are neutral," says Hall. "I can demonstrate this every day in my laboratory, and there is every reason to believe that it occurs in nature as well."
Hall's findings run counter to conventional scientific belief, which holds that mutations (changes in an organism's genetic code) occur at an even and continuous pace, and that they occur regardless of the environment. Generations of scientists since Charles Darwin have believed that mutations which make the organism more productive or successful are "selected" and are subsequently passed on more often to succeeding generations, but that the process of generating the mutations is completely separate from the process of selection. Hall's findings suggest a much more intimate relationship between mutation and selection, a relationship in which selective conditions may dramatically affect mutation itself.
"If this turns out to be widespread, we will have to revise most of what we think about the way evolution works," says Hall, whose work opens up the possibility that adaptive evolution may be considerably faster than biologists have thought up to now. The assumption that mutations are purely random forms a key part of all mathematical and theoretical studies of evolutionary processes. "The problem we face is that theory is simply not equipped to deal with these findings," says Hall.
An accurate understanding of the relationship between mutations and adaptation may be very important in trying to predict how rapidly organisms are able to adapt to polluted environments, or in estimating how likely it is that evolution can be directed toward specific ends. An example might be changing organisms in landfills so that they cause waste to decompose more quickly.
Two years ago Harvard biologist John Cairns proposed that mutations may occur at different rates depending on the stresses that an organism faces in its environment. Cairns' work has been hotly debated.
There are key differences between Hall's and Cairns' theories. Hall refers to these mutations not as "directed mutations" (as does Cairns) but rather as "Cairnsian" mutations. "`Cairnsian mutations' is a neutral term," says Hall. "This is the phenomenon, and Cairns discovered it. We don't yet know the mechanism by which it occurs; I am not saying that bacteria are directing their own evolution."
In his paper Hall proposes an explanation for Cairnsian mutations that involves an underlying random mechanism that may make some genes much more prone to mutations during times of stress.
In 1988 Hall showed that a mutation which allowed the bacterium E. coli to use the sugar salicin was the result of spontaneous excision of a mobile genetic element, or "jumping gene," from within the gene for salicin utilization. That mutation was undetectable, occurring in fewer than 2 in a trillion cells, when E. coli was growing normally, but it occurred in about 1 in 100 hundred cells when E. coli colonies were stressed by prolonged incubation on medium containing salicin in addition to other resources. The surprising observation was that the mutation occurred only when it was useful, when salicin was present, but did not occur under identical conditions when salicin was absent from the medium.
In his recent experiments Hall examined a kind of mutation that is often thought to be more important in evolutionary processes -- a mutation in which one of the bases of the DNA is changed to another base. Using strains of E. coli that normally do not produce the amino acid tryptophan, but which require it for growth, Hall deprived the bacterial colony of tryptophan for long periods of time. The result was that the deprived colonies began producing mutant strains capable of synthesizing their own tryptophan at a rate far in excess of the normal rate. His key observation was that the only mutations which increased at the accelerated pace were those related to synthesizing tryptophan -- there was no increase in the production of mutations in other genes. "It is the specificity of the process that is so surprising," says Hall. "Mutations only seem to occur at a place in the DNA where they are beneficial."
This finding of specificity, which was also the case in his earlier study, contradicts the notion that more of all types of mutations occur when bacteria starve, as was proposed by Richard Lenski and John Mittler of the University of California at Irvine three months ago.
Hall is an experimental evolutionist who uses bacteria as a model to study how organisms adapt by changing their enzymes. His work is supported by the National Science Foundation and the National Institutes of Health.
CONTACT: Barry G. Hall, (716) 275-0721, or Tom Rickey, (716) 275-7954