March 25, 2005
Researchers Trace Evolution to Relatively Simple Genetic Changes
Wild populations of stickleback fish have evolved major changes in bony armor styles (shaded) in marine and freshwater environments. New research shows that this evolutionary shift occurs over and over again by increasing the frequency of a rare genetic variant in a
single gene.
In a stunning example of evolution at work, scientists have now
found that changes in a single gene can produce major changes in the
skeletal armor of fish living in the wild.
The surprising results, announced in the March 25, 2005, issue of
journal Science, bring new data to long-standing debates about
how evolution occurs in natural habitats.
“This is one of the first cases in vertebrates where it's been possible to track down the genetic mechanism that controls a dramatic change in skeletal pattern, a change that occurs naturally in the wild.”
David M. Kingsley
“Our motivation is to try to understand how new animal types
evolve in nature,” said molecular geneticist David M. Kingsley, a
Howard Hughes Medical Institute investigator at the Stanford University
School of Medicine. “People have been interested in whether a few
genes are involved, or whether changes in many different genes are
required to produce major changes in wild populations.”
The answer, based on new research, is that evolution can occur
quickly, with just a few genes changing slightly, allowing newcomers to
adapt and populate new and different environments.
In collaboration with zoologist Dolph Schluter, at the University of
British Columbia, Vancouver, Canada, and Rick Myers and colleagues at
Stanford, Kingsley and graduate student Pamela F. Colosimo focused on a
well-studied little fish called the stickleback. The fish — with three
bony spines poking up from their backs — live both in the seas and in
coastal fresh water habitats all around the northern hemisphere.
Sticklebacks are enormously varied, so much so that in the 19th
century naturalists had counted about 50 different species. But since
then, biologists have realized most populations are recent descendants
of marine sticklebacks. Marine fish colonized new freshwater lakes and
streams when the last ice age ended 10,000 to 15,000 years ago. Then
they evolved along separate paths, each adapting to the unique
environments created by large scale climate change.
“There are really dramatic morphological and physiological
adaptations” to the new environments, Kingsley said.
For example, “sticklebacks vary in size and color,
reproductive behavior, in skeletal morphology, in jaws and teeth, in
the ability to tolerate salt and different temperatures at different
latitudes,” he said.
Kingsley, Schluter and their co-workers picked one trait — the
fish's armor plating — on which to focus intense research, using the
armor as a marker to see how evolution occurred. Sticklebacks that
still live in the oceans are virtually covered, from head to tail, with
bony plates that offer protection. In contrast, some freshwater
sticklebacks have evolved to have almost no body armor.
“It's rather like a military decision, to be either heavily
armored and slow, or to be lightly armored and fast,” Kingsley
said. “Now, in countless lakes and streams around the world these
low-armored types have evolved over and over again. It's one of the
oldest and most characteristic differences between stickleback forms.
It's a dramatic change: a row of 35 armor plates turning into a small
handful of plates - or even no plates at all.”
Using genetic crosses between armored and unarmored fish from wild
populations, the research team found that one gene is what makes the
difference.
“Now, for the first time, we've been able to identify the
actual gene that is controlling this trait,” the armor-plating on
the stickleback, Kingsley said
The gene they identified is called Eda, originally named
after a human genetic disorder associated with the ectodysplasin
pathway, an important part of the embryonic development process. The
human disorder, one of the earliest ones studied, is called ectodermal
dysplasia.
“It's a famous old syndrome,” Kingsley said.
“Charles Darwin talked about it. It's a simple Mendelian trait
that controls formation of hair, teeth and sweat glands. Darwin talked
about `the toothless men of Sind,' a pedigree (in India) that was
striking because many of the men were missing their hair, had very few
teeth, and couldn't sweat in hot weather. It's a very unusual
constellation of symptoms, and is passed as a unit through
families.”
Research had already shown that the Eda gene makes a protein,
a signaling molecule called ectodermal dysplasin. This molecule is
expressed in ectodermal tissue during development and instructs certain
cells to form teeth, hair and sweat glands. It also seems to control
the shape of - bones in the forehead and nose.
Now, Kingsley said, “it turns out that armor plate patterns in
the fish are controlled by the same gene that creates this clinical
disease in humans. And this finding is related to the old argument
whether Nature can use the same genes and create other traits in other
animals.”
Ordinarily, “you wouldn't look at that gene and say it's an
obvious candidate for dramatically changing skeletal structures in wild
animals that end up completely viable and healthy,' he said.
"Eda gene mutations cause a disease in humans, but not in the
fish. So this is the first time mutations have been found in this gene
that are not associated with a clinical syndrome. Instead, they cause
evolution of a new phenotype in natural populations.”
The research with the wild fish also shows that the same gene is
used whenever the low armor trait evolves. “We used sequencing
studies to compare the molecular basis of this trait across the
northern hemisphere,” said Kingsley. “It doesn't matter
where we look, on the Pacific coast, the East coast, in Iceland,
everywhere. When these fish evolve this low-armored state they are
using the same genetic mechanism. It's happening over and over again.
It makes them more fit in all these different locations.”
Because this trait evolves so rapidly after ocean fish colonize new
environments, he added, “we wondered whether the genetic variant
(the mutant gene) that controls this trait might still exist in the
ocean fish. So we collected large numbers of ocean fish with complete
armor, and we found a very low level of this genetic variant in the
marine population.”
So, he said, “the marine fish actually carry the genes for
this alternative state, but at such a low level it is never
seen;” all the ocean fish remain well-armored. “But they do
have this silent gene that allows this alternative form to emerge if
the fish colonize a new freshwater location.”
Also, comparing what happens to the ectodysplasin signaling molecule
when its gene is mutated in humans, and in fish, shows a major
difference. The human protein suffers "a huge amount of molecular
lesions, including deletions, mutations, many types of lesions that
would inactivate the protein," Kingsley said.
But in contrast, “in the fish we don't see any mutations that
would clearly destroy the protein.” There are some very minor
changes in many populations, but these changes do not affect key parts
of the molecule. In addition, one population in Japan used the same
gene to evolve low armor, but has no changes at all in the protein
coding region. Instead, Kingsley said, “the mutations that we
have found are, we think, in the (gene's) control regions, which turns
the gene on and off on cue.” So it seems that evolution of the
fish is based on how the Eda gene is used; how, when and where
it is activated during embryonic growth.
Also, to be sure they're working with the correct gene, the research
team used genetic engineering techniques to insert the
armor-controlling gene into fish “that are normally missing their
armor plates. And that puts the plates back on the sides of the
fish,” Kingsley said.
“So, this is one of the first cases in vertebrates where it's
been possible to track down the genetic mechanism that controls a
dramatic change in skeletal pattern, a change that occurs naturally in
the wild,” he noted.
“And it turns out that the mechanisms are surprisingly simple.
Instead of killing the protein (with mutations), you merely adjust the
way it is normally regulated. That allows you to make a major change in
a particular body region - and produces a new type of body armor
without otherwise harming the fish.”
Image: David Kingsley, HHMI at Stanford University, modified from
Cuvier (1829).
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