DURHAM, N.C. -- Science's understanding of the evolution and role of hemoglobin, considered one of the most studied and best-understood molecules in nature, is being rewritten with the help of a common intestinal parasite that infects more than 1 billion people worldwide.
A team led by Dr. Jonathan Stamler, a Howard Hughes Medical Institute investigator at Duke University Medical Center, believes that the hemoglobin molecule found in the gut of Ascaris lumbriocoides is a remnant of a crucial evolutionary junction in which anaerobic life forms, like bacteria, separated from newly emerging aerobic organisms, such as humans. The worm, in short, reveals that hemoglobin evolved first and foremost to handle the molecule nitric oxide (NO) rather than oxygen, as scientists thought, and tells the tale of when hemoglobin ceased being a "consumer" of oxygen and became a "carrier" of oxygen, Stamler said.
In a report published in the Sept. 30 issue of the journal Nature, Stamler and collaborators from Washington University in St. Louis provide biochemical proof to support this conclusion. They show that the worm actually consumes oxygen -- which it finds toxic -- with the help of NO. The discovery may yield new therapies for diseases such as cancer, in which starving tumors of oxygen is a major therapeutic focus, the researchers said.
The research was supported by grants from the National Institutes of Health and the Howard Hughes Medical Institute (HHMI).
"Both structurally and functionally, Ascaris hemoglobin is a link between bacterial hemoglobin and mammalian hemoglobin," said Washington University cell biologist Dena Minning, who, along with Duke's Andrew Gow, are co-first authors of the paper.
"Hemoglobin in bacteria is used as an enzyme to destroy NO -- the
'primordial gas' which evolved before there was oxygen and is toxic in high
amounts -- while in mammals, hemoglobin carries both oxygen and NO
Contact: Richard Merritt
Duke University Medical Center