By EurekAlert
Wednesday, September 2, 2009
The first genetic link in the evolution of the heart from
three-chambered to four-chambered has been found, illuminating part
of the puzzle of how birds and mammals became warm-blooded.
Frogs have a three-chambered heart. It consists of two atria and
one ventricle. As the right side of a frog's heart receives
deoxygenated blood from the body, and the left side receives
freshly oxygenated blood from the lungs, the two streams of blood
mix together in the ventricle, sending out a concoction that is not
fully oxygenated to the rest of the frog's body.
Turtles are a curious transition--they still have three
chambers, but a wall, or septum is beginning to form in the single
ventricle. This change affords the turtle's body blood that is
slightly richer in oxygen than the frog's.
Birds and mammals, however, have a fully septated ventricle--a
bona fide four-chambered heart. This configuration ensures the
separation of low-pressure circulation to the lungs, and
high-pressure pumping into the rest of the body.
As warm-blooded animals, we use a lot of energy and therefore
need a great supply of oxygen for our activities. Thanks to our
four-chambered heart, we are at an evolutionary advantage: we're
able to roam, hunt and hide even in the cold of night, or the chill
of winter.
But not all humans are so lucky to have an intact,
four-chambered heart. At one or two percent, congenital heart
disease is the most common birth defect. And a large portion of
that is due to VSD, or ventricular septum defects. The condition is
frequently correctable with surgery.
Benoit Bruneau of the Gladstone Institute of Cardiovascular
Disease has honed into the molecular forces at work. In particular,
he studies the transcription factor, Tbx5, in early stages of
embryological development. He calls Tbx5 "a master regulator of the
heart."
Scott Gilbert of Swarthmore College and Juli Wade of Michigan
State University study evolutionary developmental biology of
turtles and anole lizards respectively. When Bruneau teamed up with
them, he was able to examine a wide evolutionary spectrum of
animals. He found that in the cold-blooded, Tbx5 is expressed
uniformly throughout the forming heart's wall. In contrast,
warm-blooded embryos show the protein very clearly restricted to
the left side of the ventricle. It is this restriction that allows
for the separation between right and left ventricle.
Interestingly, in the turtle, a transitional animal
anatomically--with a three-chambered, incompletely septated heart,
the molecular signature is transitional as well. A higher
concentration of Tbx5 is found on the left side of the heart,
gradually dissipating towards the right.
Bruneau concludes: "The great thing about looking backwards like
we've done with reptilian evolution is that it gives us a really
good handle on how we can now look forward and try to understand
how a protein like Tbx5 is involved in forming the heart and how in
the case of congenital heart disease its function is impaired."
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