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

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...

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Autores principales: Esin, Alexander, Bergendahl, L. Therese, Savolainen, Vincent, Marsh, Joseph A., Warnecke, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777626/
https://www.ncbi.nlm.nih.gov/pubmed/29255300
http://dx.doi.org/10.1038/s41559-017-0420-3
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author Esin, Alexander
Bergendahl, L. Therese
Savolainen, Vincent
Marsh, Joseph A.
Warnecke, Tobias
author_facet Esin, Alexander
Bergendahl, L. Therese
Savolainen, Vincent
Marsh, Joseph A.
Warnecke, Tobias
author_sort Esin, Alexander
collection PubMed
description 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.
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spelling pubmed-57776262018-06-18 The genetic basis and evolution of red blood cell sickling in deer Esin, Alexander Bergendahl, L. Therese Savolainen, Vincent Marsh, Joseph A. Warnecke, Tobias Nat Ecol Evol Article 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. 2017-12-18 2018-02 /pmc/articles/PMC5777626/ /pubmed/29255300 http://dx.doi.org/10.1038/s41559-017-0420-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Esin, Alexander
Bergendahl, L. Therese
Savolainen, Vincent
Marsh, Joseph A.
Warnecke, Tobias
The genetic basis and evolution of red blood cell sickling in deer
title The genetic basis and evolution of red blood cell sickling in deer
title_full The genetic basis and evolution of red blood cell sickling in deer
title_fullStr The genetic basis and evolution of red blood cell sickling in deer
title_full_unstemmed The genetic basis and evolution of red blood cell sickling in deer
title_short The genetic basis and evolution of red blood cell sickling in deer
title_sort genetic basis and evolution of red blood cell sickling in deer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777626/
https://www.ncbi.nlm.nih.gov/pubmed/29255300
http://dx.doi.org/10.1038/s41559-017-0420-3
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