Haemoglobin (abbreviation Hb), is the iron-containing protein complex that is contained as a blood pigment in the red blood cells of vertebrates, binds oxygen and thus transports it in the bloodstream. The haemoglobin of mammals is a tetramer, consisting of 4 globins as subunits.
In adult humans, these are 2 Hb α and 2 Hb β in haemoglobin A (Hb A0), the most common form. The four proteins forming the complex are amino acid chains (α-chain 141 AAs; β-chain 146 AAs) in the fold typical of globins, each with a pocket in which an iron-II complex, haem, is bound. Its iron ion is able to bind 1 oxygen molecule. The colour of the haem changes from dark to light red.
The binding strength depends sensitively on the conformation of the protein environment of the haem. Interactions between the four globins favour the two extreme states in which the total complex is either saturated with four molecules of oxygen (in the lung) or has given up all oxygen. Interactions with other molecules support both loading and unloading.
The bee hummingbird, zunzuncito or Helena hummingbird (Mellisuga helenae) is considered the smallest hummingbird species and the smallest bird in the world. It also lays the smallest bird eggs ever, about the size of a pea. These hummingbirds weigh less than three grams, about the mass of three paper clips! The hummingbird, is endemic to Cuba. Such a hummingbird buzzes like a bumblebee in front of a hibiscus flower on the spot, like a mini helicopter in the hotel park in Cuba's capital Havana.
It breathes, even at rest, 250 times a minute. Its oxygen consumption per gram of muscle tissue is 10 times higher than that of a human athlete! Hummingbirds in the Andes survive at high altitudes and in thin air. How does this work biochemically? It's because of the red blood pigment, the iron-containing haemoglobin!
Since 2013, evolutionary biologist Jay Storz from the University of Nebraska in Lincoln has been studying the haemoglobins of 63 different hummingbird species that are native to different altitudes in the Andes. He found a correlation between the functional properties of the birds' haemoglobin and the altitude of their native habitat. Hummingbird species that live at high altitudes independently evolved haemoglobins that have stronger abilities (affinities) to bind oxygen. This was also expected.
Most surprisingly, these parallel changes in protein function involve parallel mutations on exactly the same amino acids of haemoglobin. The repetitive pattern is intriguing, Storz writes. It suggests that the molecular basis of adaptive evolution may be more predictable than previously thought.
"In principle, the repeated changes in protein function could be caused by a number of different mutations. And each time the high-altitude species evolved increasing haemoglobin oxygen affinity, it was produced by parallel changes in amino acids at the same two sites in haemoglobin. It seems that natural selection arrives at exactly the same solution every time."
Jay Storz
To determine the functional effects of the observed mutations, Storz and his colleagues use genetic engineering, which they used to synthesise the hummingbird haemoglobins for in vitro studies of protein function. They then created different mutations in the "gene-manipulated" haemoglobins to measure their effects. In addition to synthesising the haemoglobins of modern hummingbird species, the research team also reconstructed gene sequences from their ancestors to resurrect their ancestral haemoglobins.
Storz and his colleagues are now extending their scientific studies to other bird species.
"We will see if the same pattern of parallel evolution holds over larger taxonomic scales. The evolution of haemoglobin function in species living at high altitudes is a really good system for looking at questions about the predictability of evolutionary change."