Geographic Distribution of Hemoglobin Variants in the White-Tailed Deer

The genetic basis and evolution of red blood cell sickling in deer

“…Balanced polymorphisms shared between human and chimp are principally related to immune function and parasite pressure ( 46 , 47 ), so it is tempting to speculate that similar selection pressures might operate in deer, which host a number of intra-erythrocytic parasites including Babesia ( 48 ) and Plasmodium ( 49 ). Unlike in humans, however, the maintenance of two distinct alleles cannot be attributed to heterozygote advantage: Sickling homozygotes are the norm in white-tailed deer ( 20 , 22 , 50 ) and not associated with an outward clinical phenotype, indicating that the cost of bearing two sickling alleles must be comparatively low. Why, then, is the non-sickling allele being maintained?…”

“…Moreover, as in humans, sickling is reversible through modulation of oxygen supply or pH ( 9 , 17 ). As in humans, deer sickling is mediated by specific β-globin alleles ( 18 , 19 ), with both sickling and non-sickling alleles segregating in wild populations of white-tailed deer ( 20 ). As in humans, foetal haemoglobin does not sickle under the same conditions ( 19 ) and α-globin – two copies of which join two β-globin proteins to form the haemoglobin tetramer - is not directly implicated in sickling etiology ( 18 , 21 ).…”

“…At the same time, a suit of striking differences emerged: whereas human sickling occurs when oxygen tension is low, deer erythrocytes sickle under high pO 2 and at alkaline pH ( 17 ). Unlike in humans, the sickling allele (previously labelled β III ) in white-tailed deer – the only species where allelic diversity has been explored systematically – is the major allele, with a large fraction of individuals (≥60%) homozygous for β III ( 20 , 22 ). Finally, partial peptide digests suggested that sickling white-tailed deer did not carry the E6V mutation that causes sickling in humans ( 22 ), leaving the genetic basis of sickling in deer unresolved.…”

The genetic basis and evolution of red blood cell sickling in deer

“…Sickling deer erythrocytes are similar to human HbS cells with regard to their gross morphology and the tubular ultrastructure of haemoglobin polymers13–16. Moreover, as in humans, sickling is reversible through modulation of oxygen supply or pH9,17 and mediated by specific β-globin alleles18,19, with both sickling and non-sickling alleles segregating in wild populations of white-tailed deer20. As in humans, α-globin – two copies of which join two β-globin proteins to form the haemoglobin tetramer – is not directly implicated in sickling etiology18,21.…”