Adult Tibetan antelope have overcome oxygen deprivation on the high-altitude Tibetan Plateau through an unusual adaptation in which they permanently express a form of hemoglobin (the iron-containing oxygen transport protein in red blood cells) that other members of the cattle family only express as juveniles or when under extreme oxygen deprivation, according to a new study. Through a comparative genomic analysis with other bovids, Anthony Signore and Jay Storz found that a 45-kilobase region of the β-globin gene cluster - the region that encodes for the adult form of hemoglobin - was deleted in the Tibetan antelope's ancestor, causing the juvenile form (which has a higher oxygen affinity) to take its place in adult red blood cells. The findings reveal how a reversible response to oxygen deprivation that has been previously documented in adult goats and sheep became a permanent genetic fixture in a mammal that is native to a region that ranges between 3,600 to 5,500 meters above sea level. Most bovids express a fetal hemoglobin isoform with higher oxygen affinity than the adult isoform, which maintains a difference in oxygen affinity that facilitates oxygen transfer across the placenta from mother to fetus. To investigate whether and how the Tibetan antelope evolved to express this early hemoglobin isoform into adulthood, Signore and Storz characterized the genomic organization of globin genes in Tibetan antelope and other bovids using published genome assemblies, observing that the Tibetan antelope appeared to have inherited gene blocks containing the same forms of the β-globin gene as cows. Next, the researchers estimated how different forms of the β-globin gene influenced bovid evolutionary history, finding that the Tibetan antelope inherited the same three-part β-globin genes as goats and sheep, with the middle gene block containing βA (which corresponds to juvenile hemoglobin) later deleted. Through in vitro experiments, Signore and Storz confirmed that Tibetan antelope hemoglobin does, in fact, have a much higher oxygen affinity than that of all other bovids, helping to explain how Tibetan antelope can sustain running speeds of more than 70 kilometers per hour over distances of greater than 100 kilometers, at altitudes where the partial pressure of oxygen is roughly half that at sea level.
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Journal
Science Advances