A new article in Science reports on the genes that help giraffes reduce the costs of long necks

Liu, C., Gao, J., Cui, X., Li, Z., Chen, L., Yuan, Y., … & Qiu, Q. (2021). A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe. Science Advances7(12), eabe9459.

Abstract

The suite of adaptations associated with the extreme stature of the giraffe has long interested biologists and physiologists. By generating a high-quality chromosome-level giraffe genome and a comprehensive comparison with other ruminant genomes, we identified a robust catalog of giraffe-specific mutations. These are primarily related to cardiovascular, bone growth, vision, hearing, and circadian functions. Among them, the giraffe FGFRL1 gene is an outlier with seven unique amino acid substitutions not found in any other ruminant. Gene-edited mice with the giraffe-type FGFRL1 show exceptional hypertension resistance and higher bone mineral density, both of which are tightly connected with giraffe adaptations to high stature. Our results facilitate a deeper understanding of the molecular mechanism underpinning distinct giraffe traits, and may provide insights into the study of hypertension in humans.

Commentary by Barbara N. Horowitz, MD

The unique anatomic and physiologic characteristics of other species is increasingly recognized as a source of bioinspired solutions for human pathology. For centuries, the modern giraffe’s iconic neck has been the subject of fascination with much interest in understanding its functional and adaptive benefits. Giraffes have recently become the focus of biomedical investigation because, compared with other mammals, their long necks present a unique physiologic challenge for their hearts: to adequately perfuse brains which may be up to three vertical meters from the left ventricle. The increased pressure (afterload) on the left ventricle underlies the significantly elevated (when allometrically scaled and compared with other mammals) systemic blood pressures measured in giraffe (1-3). Systemic hypertension in humans and other mammals is associated with a multitude of end-organ effects and co-morbidities. Given the absence of these pathologies in healthy adult giraffes, the species and its physiology have been proposed as a natural animal model for resistance to end-organ damage common in humans with systemic hypertension.

How the kidneys, retina, cardiovascular and other systems in the giraffe are protected from the adverse effects of systemic hypertension is highly salient to human health (4-6). These evolved adaptations in giraffe may provide a blueprint for innovating solutions to intractable problems in human health. Fully characterizing the mechanisms and associated genomes which underlie these resistances is an exciting and emerging area of research in evolutionary medicine (6-8). Building on other studies of the giraffe genome (8), the Lui et al. have produced a high-quality genome assembly which advances our understanding of the pleiotropic genes associated with complex co-evolved adaptations resulting in the giraffe’s unique morphological and physiological characteristics. The authors call for more research correlating function with their genomic findings. In doing so they have pinpointed an exciting new research agenda for evolutionary medicine: to integrate broader macroevolutionary and life history perspectives with the impressive and important genomic work this paper presents.

References

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  5. Liu, C., Gao, J., Cui, X., Li, Z., Chen, L., Yuan, Y., … & Qiu, Q. (2021). A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe. Science Advances7(12), eabe9459.
  6. Horowitz, B. N., Kutinsky, I. B., Linde, A. (2020) Species-Spanning Echocardiography: Cardiovascular Insights from Across the Animal Kingdom. Curr Cardiol Rep, 22(12), 165. doi: 10.1007/s11886-020-01417-8.
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  8. Agaba, M., Ishengoma, E., Miller, W. C., McGrath, B. C., Hudson, C. N. Bedoya Reina, O. C., Ratan, A., Burhans, R. Chikhi, R., Medvedev, P., Praul, C. A., Wu-Cavener, L., Wood, B., Robertson, H., Penfold, L., Canever, D. R. (2016) Giraffe genome sequence reveals clues to its unique morphology and physiology. Nat Commun, 7, 11519.