The popular account of biological evolution as handed down from Charles Darwin is a tale told through old stones and bones, the fossil relics that show how the dinosaurs rose and fell–or how some apelike forest dwellers gave rise to today’s novelists and computer programmers.
Yet the foundation of such changes comes from a process that is all but invisible in contrast to the brute changes it produces: It is evolution on the molecular level, an astoundingly complex drama that only recently has begun to reveal its deepest secrets to biologists armed with gene sequencers and supercomputers.
Some of the most vital information being uncovered is not about change that occurs over eons but lightning-fast mutations that allow viruses such as HIV to keep one step ahead of medical science.
In fact, one especially intriguing line of research in molecular evolution has produced a potential therapy designed to make the AIDS virus evolve too fast for its own good, until it literally self-destructs.
Such expeditions into the field of molecular evolution gained rare public attention recently when a team including Chicago researchers presented a new analysis of HIV evolution that showed the epidemic started around 1930, decades earlier than many experts had thought.
New tools such as the nearly finished Human Genome Project hold the promise of even deeper knowledge, as they give an unprecedented glimpse into the saga of ancient–and ongoing–genetic wars between people and the diseases that besiege them.
Although the toil of molecular evolution researchers often takes the form of arcane theoretical debates conducted outside public view, experts such as Dr. Steven Wolinsky of Northwestern University say their work is ultimately driven by the promise of practical uses.
“If we can learn what (evolutionary) pressures there are, that will give us insights into how we can apply those pressures to develop better vaccines or treatments,” said Wolinsky, an AIDS specialist who co-authored the recent study dating the HIV epidemic.
Advances such as the genome project are also fueling a boom at the University of Chicago, which now has the world’s largest group of faculty members devoted to molecular evolution. Chung-I Wu, chairman of the school’s department of ecology and evolution, said the sudden flood of information marks the start of a new era in evolutionary research.
As biologists uncover the battles that rage at the level of proteins and DNA, they are finding striking similarities to large-scale evolutionary conflicts. Just as crabs or scorpions have evolved larger claws in an evolutionary “arms race,” the tokens of competition seem to be present in our own genes.
Wu’s team is looking at the way binding proteins on the surface of malaria parasites have struggled over the ages to overcome their chemical targets on human red blood cells.
Some preliminary work suggests the proteins in parasites and people bear “the signature of an arms race,” Wu said. It would be the first time such a molecular arms race has been demonstrated in human evolution.
The proof that people have fought retroviruses like HIV before is burned directly into the human genome, said Northwestern’s Wolinsky. Our genetic code contains the fossil remnants of retroviruses, which reproduce by infiltrating their hosts’ DNA and using the cell’s raw materials to make more copies of themselves.
HIV is so deadly in large part because it uses lightning fast evolution as a weapon.
In the course of one year, the diversification of HIV within just one infected individual can match the changes that influenza undergoes all around the world. The mutations the virus spins off in each host form not an isolated strain but a swarm of variants that experts call a “quasispecies.”
But AIDS experts now believe the high mutation rate also means HIV is “standing at the information threshold,” Wolinsky said. If the virus evolved any faster, its genetic code might be hopelessly garbled in transmission, resulting in viruses that could not infect cells or reproduce.
That’s what some researchers are counting on as the basis of a new therapy.
Several methods of exploiting HIV’s fast evolution already are being tested by Dr. Lawrence Loeb, a professor of pathology and biochemistry at the University of Washington.
Loeb’s team hopes to disable the AIDS virus by introducing compounds called nucleoside analogs. Some such agents cause “misspellings” within the chemical structure of DNA as the molecule makes copies of itself.
The problem gets worse for the virus as it pumps out more of its copies, resulting in an ever-weaker genetic signal.
“Each time the virus infects a cell it accumulates a few more errors,” Loeb said. “Most of the mutations do no harm. But eventually the virus accumulates so many errors that they inactivate it.”
Loeb and his colleagues published a study last year showing that among six analogs they tested, one succeeded in stopping HIV replication in a laboratory culture of human cells. Perhaps more important, the compound did not cause lasting damage in the human cells, which appeared able to repair the compounds’ effects.
Even as scientists explore such novel applications, some experts believe molecular evolution is on the verge of answering far more fundamental questions about how long-term changes in genes govern shifts in the ways living things function.
For example, scientists have no clue why the viral strain called HIV-1 became a worldwide killer, while HIV-2 appears to be far less lethal and limited to certain parts of Africa.
The genetic basis of human evolution poses the deepest mysteries of all.
Scientists know that humans and chimpanzees share about 98 percent of the same genes. Yet that oft-quoted fact obscures a more interesting question: Which of the remaining 2 percent caused the obvious differences that have taken root since humans and chimps evolved from a common ancestor?
The truly ambitious goal, said the U. of C.’s Wu, will be to sift through the 16 million genetic base pairs that separate people from chimps and find the changes that endowed our species with such attributes as language, cunning and a moral sense.
One new spinoff of the genome project is helping biologists trace common ailments such as heart disease to the minute genetic differences evolution has left among individual people.
Such work focuses on the smallest units of DNA variation, called single nucleotide polymorphisms–or SNPs (pronounced “snips”).
Researchers last year published the first study describing hundreds of SNPs in parts of the human genome thought to affect high blood pressure, heart disease and mental disorders.
Wu’s team is analyzing that data to shed light on basic questions such as how many helpful and bad genetic mutations humans have collected over the ages. Experts believe the least common SNPs are probably harmful mutations, which natural selection has weeded out from most people.
Good mutations appear to have entered the human genome about once every 300 to 800 years, according to Wu’s early calculations. That suggests the evolutionary obstacles confronting early humans changed often–almost at the limit of our ancestors’ ability to keep pace.
Still, many slightly harmful mutations hang on despite evolution’s tendency to remove them. Wu’s team has estimated that each person carries several thousand such tiny flaws.
“We’re not half as good as a perfect human would be,” Wu said.
