Wokół ewolucji

Wokół ewolucji

New Scientist, vol 171 issue 2300, 21/07/2001, page 30

Monsters in our midst
By Philip Cohen

Bring out the T. rex in your chicken and the ape in your aunt. The past is
coming back to life with a roar as we discover the power of evolution's
sleeping genes, says Philip Cohen

"BEEN THERE, done that, got the T-shirt, seen the movies," might be the
reaction you'd expect if you suggested bringing dinosaurs back to life.
After all, Michael Crichton cleaned up on the idea in Jurassic Park.
Today, it's almost old-fashioned.

Besides, Crichton's naive scientists generated their giant lizards from DNA
fossilised in amber. Most real-life experts argue that DNA is such a fragile
molecule that little if any authentic dino DNA still survives in the world. So
the whole notion of resurrecting dinosaurs is preposterous. Isn't it?

Perhaps not. There's another source of dino DNA-albeit modified by
millions of years of evolution. Modern birds are the closest living relatives
of the dinosaurs. Some would say that taxonomically birds are dinosaurs.
So, the reasoning goes, take some bird DNA, let evolution work on it for
the right amount of time-in reverse-and you could end up with the blueprint
for a dinosaur. Borrow a few tricks from the IVF industry, an egg or two
from a local hen house and you might just hatch a creature from the land
before time.

Still doubtful? Well, a few years ago, plenty of people were. But the
success of a small group of pioneers who have recreated ancient genes and
given snakes back the rudiments of their long-lost legs and hens their teeth,
is starting to convince the sceptics. "The technology will be there," says
David Stern, an evolutionary biologist at Princeton University. "Things are
happening so rapidly now." Just two years ago, Stern predicted that
scientists would take two centuries to resurrect a dinosaur. "Now I'd guess
more like 60 to 100 years," he says.

The research that might make this resurrection possible stems from the
fusion of two hot new fields: the evolution of development (evo-devo for
short) and comparative genomics. This scientific merger does not have
dinosaurs at its focus, however. The main reason biologists want to rewind
evolution is so they can run it on fast-forward. After all, evolution has been
solving problems by manipulating genes for hundreds of millions of years.
Why should today's genetic engineers reinvent the wheel as they try to
regrow severed limbs, say, when they can copy Mother Nature (see
"Evolution lends a hand")?

Up to now, nobody has actually signed up for what might be called the
Jurassic Chicken Project. But it's certainly being discussed and the
groundwork has been laid. A small cadre of scientists has begun retrieving
long-lost genomic data. Just as linguists can reconstruct long-lost tongues
by looking for the common roots among modern languages, so geneticists
can infer what ancestral genes must have looked like by comparing the
genomes of descendants that have a common ancestor, says Steven Benner
of the University of Florida in Gainesville. Benner's team recently
reconstructed a gene that resided in a Cretaceous yeast, a microbial
contemporary of Tyrannosaurus rex, 70 million years ago.

The most treasured skill of modern brewer's yeast, Saccharomyces
cerevisiae, is its ability to ferment sugars into alcohol with the help of the
enzyme alcohol dehydrogenase (ADH). Brewer's yeast has several versions
of this gene, all derived from a single ancestral copy. Benner's team
compared them with ADH sequences from related yeasts, and worked out
the sequence of their common ancestor.

Then they brought the sequence to life using genetic engineering tools to
recreate the gene and produce the ancient enzyme for the first time since
dinosaurs walked the Earth. When they tested its biochemical powers, they
found something surprising. The enzyme was optimised to consume
alcohol rather than create it. Brewer's yeast began not as a brewer, but
as a lush.

The same approach could be used to derive a dinosaur genome with the
help of modern birds. Comparing the genomes of different birds would
yield an ancestral, dinosaurian genome. Recreate the genome, and the rest
is straightforward. Pop a synthesised T. rex genome, say, into a bird egg of
the right size and a Tyrannosaurus should hatch out.

Of course, reconstructing entire genomes would be vastly more challenging
than single genes. It could involve more than 30,000 genes and millions of
individual changes. Even humans and chimps, who have at least 97 per cent
of their DNA in common, have roughly 90,000,000 differences in their
genome-and you might expect many times that number between a chicken
and a dinosaur. But DNA sequencing and computing are advancing at such
a pace that a century from now, it may be possible to crunch the genomes
of several key species on Saturday and finish the genetic analysis on a
hand-held computer by Sunday brunch.

That would get us closer to making a T. rex, but not all the way, says John
Gatesy of the University of California, Riverside. The common ancestor of
modern birds would be a distinctly bird-like creature, not much like the
giant monsters that most capture our imagination. You could try bringing
the next closest relative of dinosaurs, crocodiles, into the comparison, but
the common ancestor of birds and crocs lived about 250 million years ago-
before the dinosaurs-so these kinds of genetic studies will hit either side of
the mark. "You are going to have to make a lot of educated guesses," says
Gatesy.

Still, salvaging even a few Jurassic genes could yield important insights.
For instance, most experts are convinced that dinosaurs were warm-
blooded, but the issue is still highly contentious. Study the heat tolerance of
a few resurrected enzymes and the issue could be settled once and for all.

In fact, scientists reckon that most of the genes that build a chicken would
be functionally interchangeable with their counterparts in a dinosaur. One
of the revelations of the past decade of developmental biology is the
astounding degree to which the same kinds of gene perform the same
function in a wide variety of organisms. The classic examples are the hox
genes, which appeared in a primitive ancestor of all multicellular life some
700 million years ago. They establish the general blueprint for the
organism's structure of head, body, tail. Organisms as diverse as worms,
flies, fish and humans all have versions of these genes, and they seem to be
interchangeable. Move the human gene to a fly, for example, and it still
does the job.

The similarity between genomes probably goes even deeper. Sets of genes
often work together to achieve the same result across a huge variety of
species, implying that these molecular circuits were established very early
in evolution. In all vertebrate limb development, for example, two proteins
known as sonic hedgehog and fibroblast growth factor help promote the
growth of the embryonic limb bud by switching on an array of genes. "I've
never seen a triceratops," says Cliff Tabin of Harvard University. "But
those same molecules built its limbs."

Identifying the developmental genes is probably the easy part, though.
Much tougher will be finding all the various sequences that turn them on
and off at the right times and places in the developing embryo. In theory,
you should be able to reconstruct these regulatory switches in the same
way as the genes themselves. But because regulatory regions are often
buried in apparently non-functional or "junk" DNA, biologists have a hard
time just finding them, let alone deciphering their effect.

This could be where the Jurassic Chicken Project hits a brick wall. As we
try to reconstruct dinosaur genomes, there are bound to be important
regions where we simply won't know how the genes were regulated. Some
regulatory regions evolve so quickly that they will have been rewritten
many times since the Cretaceous, making it impossible to reconstruct the
original. To bridge the gaps, biologists will need to understand how those
genes contribute to every single tissue in the developing organism, and then
construct suitable regulatory regions from scratch. "That's too complex to
understand completely, maybe even in a living animal," says Jeremy
Gibson-Brown of Washington University in St Louis. Worse still, a given
gene can be used for many different purposes during the development of an
organism, posing further headaches for would-be dino designers. "Fix gene
regulation in one tissue and you run the risk of ruining another. I don't
think it is realistic," says Tabin.

But optimists point out that what may appear to be major differences
between species can sometimes be created or removed with surprising ease.
All it takes is the right molecular signal. In one striking example, Cheng-
Ming Chuong of the University of Southern California in Los Angeles and
his colleagues were able to get the beaks of chicken embryos to grow the
buds of teeth, a structure bird ancestors lost some 60 million years ago
(Proceedings of the National Academy of Sciences, vol 97, p 10,044). All
it took to erase the years of evolution was beads soaked with fibroblast
growth factor placed in the embryo's mouth. Researchers have partially
restored legs to snakes and eyes to eyeless cave fish with similar ease. "In
some cases, these ancient circuits are probably still there," says Martin
Cohn at the University of Reading. "All we need to do is plug them in."

Unplugging a circuit added during evolution should be even easier.
Feathers, for instance, are an elaboration of scales, so getting rid of them or
halting them at some earlier stage of development shouldn't be very hard,
says Chuong, who also studies feather evolution. Indeed, scientists
studying mammalian hox genes found that inactivating certain hox genes in
mice gave them backbones more akin to those of their ancestors who lived
more than 200 million ago (New Scientist, 28 October 1995, p 30).

So it shouldn't be too hard to create a toothy, scaly chicken. And some of
the other changes needed to make a dinosaur may be even easier. In one
notable experiment, biomechanics specialists Matthew Carrano of the State
University of New York at Stony Brook and Andrew Biewener of Harvard
University fastened metal tails onto chicks. They wanted to see whether the
redistribution of weight and torsion would make them stand more upright
and result in a thinner, more dinosaur-like femur.

In one respect, the experiment was a complete failure: instead of standing
tall, the chicks dealt with the weight by crouching even lower. But that did
affect their bones-they became even less dinosaur-like (Journal of
Morphology, vol 240, p 237). This suggests to Biewener that posture helps
determine the bone structure. So if scientists can genetically engineer the
chicken hip to give it a more upright posture, it might automatically cause
the rest of the leg to become more dinosaur-like. "The body may be doing
a lot of adapting to a few genetic changes," Biewener says.

If dino engineers do someday manage to turn back the clock, though, even
the most optimistic experts say the best that might emerge from the egg
would be a sort of generic dinosaur. Too many details have been lost along
the way to faithfully recreate a particular species. And soft details such as
skin colour and behaviour, long lost in the fossil record, would essentially
have to be invented. But perhaps with enough tinkering-to stretch out
claws, elongate necks or increase body size-it may eventually be possible to
create "dinosaurs" realistic enough for anyone's dream or nightmare.

The real barriers to the JCP may in fact be ethical rather than scientific. If
we can revive dinosaurs, why not turn back the clock on human evolution
too, turning a chimp into a facsimile of an australopithecine, say? "If
something is possible then someone is going to try it," says Stern. "We
have 50 to 100 years before this happens, and we need that much time to
think about the ethical implications."

Other questions will crop up, too. Should we try to atone for centuries of
environmental damage by restoring species that humans have wiped out?
What would be the environmental impact if these animals escaped or were
released? Some of these issues are already being raised by the controversy
over genetically modified food and plans to clone rare or extinct species.
The JCP pushes the boundaries much further.

But because of its practical importance, the revolution in evo-devo and
genomics doesn't depend on there being a Tyrannosaurus at the end of the
rainbow. "Looking back on the Wright brothers' plane, it was clear there
would be jets someday," says Rudolph Raff of Indiana University. Right
now, he admits we have only a dim view of what the future holds. "But I
think that the amount of engineering that is possible will match anything in
any science fiction imagination."

Evolution lends a hand
THE melding of evo-devo and comparative genomics offers vast
possibilities. Once we learn how evolution has manipulated the genetic
switches that control development, we may be able to borrow the
techniques to redesign livestock and crops to make much more profound
changes than we can achieve with today's limited tinkering.

Likewise, medical researchers who know how to elongate a limb, make a
head smaller or alter the shape of a heart may someday use that knowledge
to diagnose and correct birth defects that result when the same genes go
awry. And armed with a deeper understanding of how genes and cells
collaborate to create the parts of the body, doctors will have a better
chance of regrowing missing or damaged limbs, rejuvenating arthritic
knees, replumbing clogged arteries, or coaxing human cells to grow into
transplant organs in the lab.

"We'd like to learn from the way evolution solved those problems," says
Cheng-Ming Chuong of the University of Southern California in Los
Angeles. "We want to learn how to grow an arm. We know nature learned
how over millions of years of trial and error, so that's what we study."
Some evolutionary biologists go even further. The really interesting
questions, they say, lie much further back in the history of life. Jeremy
Gibson-Brown of Washington University in St Louis and his colleague Ilya
Ruvinsky at Harvard University, for instance, are studying genetic events at
the evolutionary branching that led to vertebrates. They want to answer
such basic questions as why vertebrates developed limbs at all.

The people with the money are starting to take notice. The US National
Science Foundation has begun a special evo-devo programme to fund this
type of work, and universities are beginning to establish new research
positions in the subject. What's more, the revolution in genomics is giving
the whole field new tools to work with. Expect evo-devo to become one of
the hottest research areas of the 21st century.

Philip Cohen

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