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

Abstract

Crescent-shaped red blood cells, the hallmark of sickle cell disease, present a striking departure from the biconcave disc shape normally found in mammals. Characterized by increased mechanical fragility, sickled cells promote haemolytic anaemia and vaso-occlusions and contribute directly to disease in humans. Remarkably, a similar sickle-shaped morphology has been observed in erythrocytes from several deer species, without obvious pathological consequences. The genetic basis of erythrocyte sickling in deer, however, remains unknown. Here, we determine the sequences of human β-globin orthologs in 15 deer species and use protein structural modelling to identify a sickling mechanism distinct from the human disease, coordinated by a derived valine (E22V) that is unique to sickling deer. Evidence for long-term maintenance of a trans-species sickling/non-sickling polymorphism suggests that sickling in deer is adaptive. Our results have implications for understanding the ecological regimes and molecular architectures that have promoted convergent evolution of sickling erythrocytes across vertebrates.

Natural History of Plasmodium odocoilei Malaria Infection in Farmed White-Tailed Deer

“…Precise calculation of the EIR for P. odocoilei in Florida will rely on future studies of local mosquito sampling and calculation of the (likely substantial) mosquito biting rate for O. virginianus , but existing evidence suggests the EIR is comparable to that of human malaria in sub-Saharan Africa. Intriguingly, several deer species possess globin polymorphisms that cause erythrocyte sickling, and recent evolutionary studies suggest that these genetic changes may be undergoing positive selection ( 27 ). Human sickle cell heterozygosity confers protection against severe malaria ( 28 ).…”

Infinite Assembly of Folded Proteins in Evolution, Disease, and Engineering

“…Although the agglomeration of hemoglobin is associated with pathologies in humans, red blood cells in some species of deer naturally exhibit a sickle shape. The sickling mechanism was recently also attributed to a glutamate‐to‐valine change, albeit in a different part of the structure . In contrast to the human case, deer hemoglobin also agglomerates in the oxygenated form.…”

Infinite Ansammlungen gefalteter Proteine im Kontext von Evolution, Krankheiten und Proteinentwicklung

“…Während die Agglomeration von Hämoglobin beim Menschen pathogenetisch wirkt, zeigen die roten Blutkörperchen in einigen Hirscharten eine natürliche Sichelform. Als dafür verantwortlicher Mechanismus wurde ebenfalls ein Austausch von Glutamin gegen Valin identifiziert, jedoch an einer anderen Stelle der Struktur . Im Unterschied zum Hämoglobin des Menschen agglomeriert das der Hirsche auch in der oxygenierten Form.…”