Comparing the hemoglobins of animals including the mouse and the elephant shows that these proteins have evolved specific characteristics to meet the oxygen demands of creatures of various sizes. Image credit: Public domain
In humans and other mammals, a protein in the blood called hemoglobin carries oxygen from the lungs to other parts of the body. This protein contains four subunits that can each bind to one molecule of oxygen, so a single hemoglobin can carry up to four oxygen molecules at the same time. Previous studies have found that, although each subunit can potentially bind oxygen on its own, the subunits actually work together to help each other bind to oxygen in the body.
Two biochemical properties of hemoglobin affect how it carries oxygen molecules. First, oxygen-binding affinity, or how tightly the protein can bind to oxygen; and secondly cooperativity, or the degree to which the subunits interact with each other to bind oxygen more tightly. Mammals of different shapes and sizes have different requirements for transporting oxygen from the lungs to organ tissues, which have shaped their hemoglobin proteins over evolutionary timescales. While the contribution of affinity to hemoglobin evolution in animals of different sizes has been addressed in the past, the role of cooperativity in hemoglobin adapting to body size has remained unclear.
Here, Rapp and Yifrach used a mathematical approach to analyze existing data from 14 different mammals – including mice, sheep, humans and elephants – on how oxygen binds to hemoglobin. Using this approach, they were able to explain why different mammalian hemoglobins present different oxygen-binding affinity and cooperativity values. Furthermore, they demonstrated that the cooperativity values were very close to the maximum they could be for each version of hemoglobin.
These findings suggest that, as mammals evolved, genetic mutations that altered the oxygen-binding affinity or the ability of hemoglobin subunits to cooperate may have allowed hemoglobin proteins to adapt to meet the oxygen needs of mammals of different sizes and shapes. In the future, the approach used by Rapp and Yifrach could be adapted to study how other proteins that bind molecules in a cooperative manner have evolved.
