struggled mightily to slay the nine-headed Hydra in the swamps of Lernea,
contending with two new heads that sprouted whenever he dispatched one.
What he didn't know was that he needed only to knock
out a gene.
Daniel Martinez, an assistant professor of biology at
Pomona, has helped uncover a molecular switch that appears to have a role
in the making of a head in the hydra, a tiny, tubular invertebrate with
a mouth encircled by tentacles, giving it more than a passing resemblance
to its mythical namesake. It's too late to be of use to Hercules, but
the discovery of this gene operating in a primitive creature like the
hydra is important in advancing our understanding of the history and diversity
of life on Earth.
The hydra familiar to biologists is in the phylum Cnidaria,
which includes jellyfish and corals. On the evolutionary tree, this phylum
consists of the lowest forms of animals that exhibit a recognizable body
plan. Under evolutionary theory, Cnidarians and all the animals higher
on the tree, including humans, shared a common ancestor. Martinez is among
scientists who are probing the biological mechanisms at work in some of
nature's humblest animals to help shed light on the makeup of much more
complex metazoans, such as people.
In the hydra's simplicity lies its allure, says Martinez,
whose office in Seaver South is adorned with colorful, artfully molded
jellyfish floating on filaments from the ceiling.
"Let's imagine that we want to study the basics of how
cars function," he says. "Would you study a Model T or a Lexus? If you
open a Lexus hood, there are computers, there are emissions controls,
there are all kinds of things that are not essential for a car to function.
So if you want to study the basics of the car, you go for a Model T. And
if you want to study what makes an animal an animal, the basic genes that
control development, you cannot study humans, because we are like a Lexus.
We have all kinds of complications that are basic for us as a human, but
are not basic for us as an animal. By studying a primitive creature, the
hydra, we can look at the genes that regulate development—some of the
same genes that are in you and me—and see what they were doing at the
The life of a hydra, as for other metazoans, begins
with a cell that starts to divide. One of the first steps is the formation
of a sort of hollow ball, which then develops into a saclike structure
with a mouth at one end and an anus at the other: a primitive gut. This
early stage of embryonic development is called gastrulation, and scientists
have found that a particular region of the embryo is essential in driving
the process: If this region, called the organizer, is removed, gastrulation
cannot occur. If it is removed from one embryo and transplanted into another,
it creates a tandem pair of connected creatures, with two organizers driving
Certain genes in the organizer region have been identified
as having critical roles in the development of an animal. One such gene,
found to operate in the organizers of frogs, is called pintallavis. Martinez
and his research associates have found a homologous gene operating in
the hydra. In the hydra, Martinez calls it budhead. How it works would
have been of intense interest to Hercules.
"If you take a piece from the head of one hydra and
transplant it into the body column of another hydra, the transplanted
tissue organizes the tissue around it to form a head, resulting in a two-headed
hydra," says Martinez. "The gene that we found, that I called budhead,
is expressed in a region that we can call the organizer of hydra. This
is the same gene that is expressed in the organizer of frogs, and this
gene also exists in humans. So humans and hydra seem to share a gene that
has something to do with the organizer in embryos."
Another gene also has been found to be associated with
the organizer in both the frog and the more primitive hydra, and Martinez
says he and other researchers are seeking to establish how these genes
work together. "We know that if we knock out these genes, the organizer
loses some of its properties in the frog, and we have found these same
two genes together in hydra," he says. "We are starting to build a network
of genes that we find are involved in the organizer of frogs that also
seem to be involved in the organizer of hydra, and what this suggests
is that these genes were really working together early on in animal evolution."
The discovery of such homologous genes operating in
very similar ways in diverse forms of life is just one of the remarkable
developments in a new field known as the evolution of development, a fusion
of two distinct subdisciplines of biology. For centuries, scientists studying
development have focused on the ontogeny of a species; that is, on the
process that transforms a single-celled zygote into a complete (albeit
little) animal. Since Darwin, evolutionists have studied changes that
occur in a plant or animal species through a historical line of descent,
or phylogeny. The new approach combines elements of both, and is called
evo-devo for short.
"When we're talking about development, we're talking
about how genes switch on and off in different cells to control the transformation
of a fertilized egg into a complete organism," says Martinez. "Students
of evo-devo want to determine how animal development has changed though
evolutionary time to generate all the different kinds of animals that
we see today. We want to understand how the molecular machinery has been
built up to produce animals as complex as flies or humans."
One of the nascent field's most astonishing findings
has been that the same molecular machinery is used to make animals as
seemingly incongruous as an elephant and a butterfly.
"If you had asked an embryologist 20 years ago about
whether the same genes were going to be involved in creating something
so different as a grasshopper or a sea urchin or a human, they would have
said no, no way. The embryos are too different," says Martinez. But it
was found that both in humans and in Drosophila, the fruit fly, sets of
molecular switches known as homeobox genes not only are homologous in
structure, but are also very similar in function: In fruit flies and in
people, and in other organisms as well, they help guide the development
of embryos by specifying aspects of the body axis.
"That discovery gave us the chance to start studying
development from an evolutionary point of view," says Martinez, who is
an evo-devo specialist. "Now we want to say: Okay, these animals are using
the same genes, but they obviously are used in different ways, because
you either get a fruit fly or a mouse or a human. So, what is the difference?"
That is where Martinez's work with the hydra comes in.
Because genes can acquire new functions through evolutionary time, a finding
such as the one he and his associates made with the hydra is important
in helping to pinpoint alterations, or the lack of them, in patterns of
gene expression over the course of time. Martinez's findings suggest that
the function of some genes associated with the organizer seems to have
been maintained through many layers of phylogeny.
"We have found that humans and fruit flies share genes
that control development," Martinez says. "So we can go farther down the
evolutionary tree and ask: Do hydras have the same genes that control
development? And if so, how have they changed over time? By studying a
simple creature, we have a better chance of understanding what makes an
animal an animal, from a developmental point of view. Then, once we have
that basic element determined, we can study evolution. We can say: How
now, from this basic plan, can we make a human? What are the things we
need to add to a Model T to make it a Lexus? And then we can see what
is primitive, and what is derived. We can see what was there at the beginning,
and we can see all of the complexities that have been added through time
to make your body plan different from that of the simpler creatures."
The complexities that account for nature's grandeur--so
much of it still a mystery--helped draw Martinez to evo-devo studies.
A graduate of Universidad Nacional del Sur in Argentina and the State
University of New York at Stony Brook, he expected to become an ecologist.
"But when I learned more about evolution, I became fascinated by it,"
he says. "To look at the process of development from an evolutionary point
of view is fascinating. Today we are tackling one of the most significant
questions in biology: Why do animals look the way they do? What molecular
processes make a snail different from a bird?
"We are trying to elucidate the basic instructions to
build a snail and a bird, and then compare those instructions to determine
similarities and differences. The diversity of animals that we see today
is created through development. But development, like all the other features
of an organism, has evolved. Trying to figure out the changes required
to make a Lexus out of a Model T is not only an incredibly enlightening
exercise, but also a lot of fun." --Michael Balchunas