now for news from the genetic twilight zone
is the genetic basis of evolutionary change? What forces cause
different species to evolve?
all know how evolution occurs: during the multitudinous molecular
busywork of dividing and splicing, somewhere some random genetic
blip crops up. The mutation most likely has no effect, or it may
provide an advantage and even become the point at which a new
species splits off.
Evolutionary biologist Chung-i Wu has found that competitive
pressures actively shape as much as 25 percent of fruit
fly genes - mainly those involved in sex and immunity.
chance is how biologists, or those who study genotypes at least,
explain evolution. But Chung-i Wu, chair and professor of ecology
& evolution and himself a student of genotypes-that is, a
group's genetic makeup-doesn't see it that way. Nor, he points
out, is that the view of evolution embraced by biologists who
study phenotypes-the visible properties of groups that are produced
by the genotype's interaction with the environment. Their observations,
like Darwin's before them, prove that natural selection plays
a much more active role than the word random implies.
a discrepancy between molecules and morphology," says Wu.
"On one hand, we can see by looking at breeds of dogs and
even humans the difference in morphology. But when we measure
the differences among groups in the same species at the genetic
level, the differences vanish."
would like to reconcile these views. He believes natural selection
plays a major role even at the genic level and, in competitive
environments, actually speeds up.
sex genes, which evolve much faster than other genes, as Wu, postdoctoral
fellow Wen Wang, and Gerald Wyckoff, PhD'00, noted in a January
2000 Nature study. Genes that resist diseases evolve at
a faster pace too. The gene that fights malaria, according to
preliminary findings by one of Wu's graduate students, is the
fastest evolving gene in the human body. In this year's February
28 Nature Wu, Justin Fay, PhD'01, and Wyckoff reported
that as many as one in four fruit-fly genes show evidence of ongoing,
rapid evolution. And most of those rapidly evolving genes are
involved in fighting diseases or reproducing the species, areas
where, says Wu, there is "continually room for improvement."
why do most molecular evolutionists still espouse the random-chance,
or "neutral" view of evolution? The theory, conceived
in the 1960s and still dominant in the genomic era, states that,
of the many small genetic changes that randomly occur, the vast
majority simply do not matter, and less than 1 percent make enough
difference to be embraced by natural selection.
theory dominates partly "because it's elegant and aesthetically
appealing," says Wu, who trained as a neutralist under geneticist
Mastoshi Nei at the University of Texas and whose down-to-earth
manner reflects his pragmatic view of molecular evolution. During
the 1930s heyday of neo-Darwinism, he explains, biologists intuited
that "probably every piece of DNA was subjected to natural
selection." But by the 1960s scientists were able to study
DNA directly, and the genome's sheer size-thousands of teeny tiny
molecules laid bare to the forces of natural selection-overwhelmed
knew from artificial selection and the domestication of animals
that you cannot improve a stock rapidly; there's a limit to how
much selection can be tolerated by a species," Wu continues.
But direct observations showed that the genome was undergoing
many changes at many points. If they were all the product of natural
selection, evolution would move too quickly for a species to digest
it. So a Japanese geneticist named Motoo Kimura proposed neutral
theory, placing the power of evolution in the hands of random
"genetic drift," with the rare occurrence of "good"
mutations. "It's survival of the unscathed," says Wu,
"preservation of the status quo."
research team takes an approach that he says the neutral theory
all but killed: "screening populations for good mutations
and finding out why they're good," that is, pinpointing the
exact locations along the genetic code where advantageous mutations
led to a new species. The easiest way to do this is to study fruit
flies, which are genetically simple creatures, relatively speaking.
For the most recent Nature study, the team did a blanket
survey, tallying the minute variations within each of 45 genes
among flies of one species (Drosophila melanogaster) and
contrasted those with the same genes from a different species
found that competitive pressures were actively shaping 11 genes-mainly
those involved in sex and immunity-while 34 genes, or about 75
percent, showed no sign of natural selection. Next Wu's team turned
to the recently completed map of the human genome and extrapolated
their results to see if humans evolved at similar genetic locations.
By studying variation within human genes and comparing them with
genes from old-world monkeys, the researchers found that survival
of the fittest is just as active in humans as in fruit flies.
Comparing variation within the human genome and divergence from
ape ancestors, they determined that about 35 percent of the accumulated
changes in humans were "good," that is, provided humans
with advantages that contributed to speciation. That's a "shockingly
high" proportion, says Wu. It means one advantageous substitution
has entered the human genome every two centuries since humans
separated from monkeys.
study the team publishes advances Wu's molecular adaptation theory-his
cure for the vertigo molecular evolutionists experience when confronted
by the sheer size of the genome and the possibilities for natural
selection to wreak havoc on it. "Just because the stock market
goes up 10 percent in one week, doesn't mean it will go up 520
percent over a year's time," says Wu. In other words, the
most commonly made mistake is to extrapolate an observation made
over a short time period to the vast expanse of evolutionary time.
who also has appointments in molecular genetics & cell biology,
the Committees on Genetics and Evolutionary Biology, and the College,
doesn't have that luxury. He deals with both morphology and molecules-two
worlds that "generally agree to be separate and equal. But
true biologists," he says, "ought to be able to traverse
the two. I have seen the vicissitudes of life in the lab. The
theory isn't adequate to explain what we see."
completion of the Human Genome Project, Wu's team has been racing
toward a genomic approach: where before it could only study three
genes at a time, now it is studying 150 and soon will be able
to study 1,000. "The scale itself makes our work qualitatively
different," he says. The more genes he's able to study, the
more he's able to hammer his molecular adaptation theory into
the pages of peer-reviewed journals-which paves the way for his
work on speciation.
unfortunate result of neutral theory, he notes, is that molecular
evolutionists have failed to study how speciation occurs-that
is, where and why those "good" mutations happen. Their
focus tends to be on differences that occur within species and
similarities that occur across species. Little has been done to
explain how species differ from their closest relatives. "There
are 30 to 40 million differences in the human and the chimp genetic
sequences," notes Wu, "but we cannot identify a single
one and say, That is the one that makes humans smarter or chimps
hairier or the jaw protrude."
gene that both humans and mice share, says Wu, "is simply
not interesting to me. I admit it may be important-but in a physical
sciences kind of way. Physical scientists look for the general
principles that explain life: an apple falling from a tree, sound
from a violin. But if there's a way to define what this department
does as opposed to what they do on the other side of Ellis, it's
our interest in the differences between species. The end
of population genetics," he continues. "is the be- ginning
of speciation. That's the twilight zone no one wants to touch.
That is where the neutral theory's limits become clear."
Wu really needs is to take a genomic approach to monkeys too:
so that he can measure human variations directly against those
of our closest relatives. The problem is, the next genome scheduled
to be completed is the mouse. "That's not useful. Mice are
too different from humans!" he grumbles. So he's assembling
an international consortium of universities in Japan and Taiwan
and the U of C. Its goal, if the National Institutes of Health
agrees to fund Chicago's portion, is to sequence the protein-coding
portion of the genome of the Asian macaque, and begin demonstrating
more precisely just how unrandomly natural selection has
driven the monkeys and humans apart.
on his neutralist training, Wu calls the theory "very efficient.
But life is very messy, not elegant at all." Neutralism and
molecular adaptation, he says, are like Hemingway and Faulkner.
"Hemingway's prose is simple and beautiful, but Faulkner
is probably more true to life."