Image: Patrick Gillooly |
Ever
since Charles Darwin proposed his theory of evolution in 1859, scientists have
wondered whether evolutionary adaptations can be reversed.
Answering
that question has proved difficult, partly due to conflicting evidence. In
2003, scientists showed that some species of insects have gained, lost, and
regained wings over millions of years. But a few years later, a different team
found that a protein that helps control cells’ stress responses could not evolve
back to its original form.
Jeff
Gore, assistant professor of physics at MIT, says the critical question to ask
is not whether evolution is reversible, but under what circumstances it could
be. “It’s known that evolution can be irreversible. And we know that it’s
possible to reverse evolution in some cases. So what you really want to know
is: What fraction of the time is evolution reversible?” he says.
By
combining a computational model with experiments on the evolution of drug
resistance in bacteria, Gore and his students have, for the first time, calculated
the likelihood of a particular evolutionary adaptation reversing itself.
They
found that a very small percentage of evolutionary adaptations in a
drug-resistance gene can be reversed, but only if the adaptations involve fewer
than four discrete genetic mutations. The findings will appear in Physical Review Letters. Lead authors of
the paper are two MIT undergraduates, junior Longzhi Tan and senior Stephen
Serene.
Evolving resistance
Gore and his students used an experimental model system developed by
researchers at Harvard
Univ. to study the
evolution of a gene conferring resistance to the antibiotic cefotaxime in
bacteria.
The
Harvard team identified five mutations that are crucial to gaining resistance to
the drug. Bacteria that have all five mutations are the most resistant, while
bacteria with none are very susceptible to the drug. Susceptible bacteria can
evolve toward resistance by gaining each of the five mutations, but they can’t
be acquired in any old order. That’s because evolution can only proceed along a
given path if each mutation along the way offers a survival advantage.
Scientists
study these paths by creating a “fitness landscape”: a diagram of possible
genetic states for a particular gene, and each state’s relative fitness in a
given environment. There are 120 possible paths through which bacteria with
zero mutations could accumulate all five, but the Harvard team found that only
18 could ever actually occur.
The
MIT team built on that study by asking whether bacteria could evolve resistance
to cefotaxime but then lose it if they were placed in a new environment in
which resistance to the original drug hindered their ability to survive.
Genetic
states that differ by only one mutation are always reversible if one state is
more fit in one environment and the other is more fit in the other. The MIT
researchers were able to study how the possibility of reversal decreases as the
number of mutations between the two states increased.
“This
is the first case where anyone’s been able to say anything about how
reversibility behaves as a function of distance,” Gore says. “What we see in
our system is that once the system gets four mutations, it’s unable to get back
to where it started.”
Daniel
Weinreich, assistant professor of biology at Brown Univ.,
says the study’s most important contribution is its analysis of the
reversibility between every possible intermediate state in the fitness landscape.
“What
Jeff has done is show that there’s another layer of mathematical complexity
that enters when you ask questions about reversing environmental pressure,”
says Weinreich, who was not involved in this research.
Reversing complex adaptations
In the late 19th century, paleontologist Louis Dollo argued that evolution
could not retrace its steps to reverse complex adaptations—a hypothesis known
as Dollo’s law of irreversibility. Gore says his team’s results offer support
for Dollo’s law, but with some qualifications.
“It’s
not that complex adaptations can never be reversed,” he says. “It’s that
complex adaptations are harder to reverse, but in a sense that you can
quantify.”
The
study also helps explain why organs no longer needed, such as the human
appendix, do not readily disappear. “You can only ever really think about
evolution reversing itself if there is a cost associated with the adaptation,”
Gore says. “For example, with the appendix, it may just be that the cost is
very small, in which case there’s no selective pressure to get rid of it.”
In
a follow-up study, the researchers are looking at how the rate of environmental
change affects the reversibility of evolution. In the Physical Review Letters study, they
assumed an immediate switch between two environments, but they believe that
more gradual changes might alter the rate of reversal.
