Sunday, September 06, 2009

Evolution of the 4-Chambered Heart

Reptilian heart development and the molecular basis of cardiac chamber evolution. 2009. K. Koshiba-Takeuch, et al. Nature 461: 95-98.

The cold-blooded reptilian heart in action.
Young Romance #1 (1947) by Simon & Kirby
Scientists have traced the evolution of the four-chambered human heart to a common genetic factor linked to the development of hearts in turtles and other reptiles.
"This is the first genetic link to the evolution of two, rather than one, pumping chamber in the heart, which is a key event in the evolution of becoming warm-blooded," said Benoit Bruneau. "The gene involved, Tbx5, is also implicated in human congenital heart disease, so our results also bring insight into human disease."

With four chambers—two atria and two ventricles—humans and all other mammals have completely separate blood flows to the lungs and to the rest of the body, which is essential for us to be warm-blooded. The different reptiles offer a sort of continuum from three to four chambers.

To better understand reptile heart evolution, the scientists examined the transcription factor Tbx5. Mutations in the human gene that encodes Tbx5 result in congenital heart disease and, in particular, defects in the ventricular septum, the muscular wall that separates the ventricle into two sections. Levels of Tbx5 is a key player in the evolution of septum development between the left and right ventricles.

The team looked at Tbx5 distribution in the turtle and the green anole lizard. During the early stages of heart formation in both reptiles, Tbx5 activity is found throughout the embryonic ventricular chamber. In the lizard, which forms only one ventricle, this pattern stays the same as the heart develops. However, in the turtle, which has a primitive septum that partially separates the ventricles into left and right sides, distribution of Tbx5 is later gradually restricted to the area of the left ventricle, resulting in a left-right gradient of Tbx5 activity. This meant that the gradient of Tbx5 forms later and less sharply in the turtle than in species with a clear septum, such as mammals, providing a tantalizing clue about how septation evolved.

Further evidence from mice conclusively showed that a sharp line delineating an area of high level of Tbx5 is critical to induce formation of a septum between the two ventricles. link