Giraffe genes that cope with long necks

Giraffe genes that cope with long necks

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.


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.


  1. Aalkjær, C. and Wang, T. (2021). The remarkable cardiovascular system of giraffes. Annu. Rev. Physiol. 83, 1–15.
  2. Østergaard, K. H., Baandrup, U. T., Wang, T., Bertelsen, M. F., Andersen, J. B., Smerup, M. and Nyengaard, J. R. (2013). Left Ventricular Morphology of the Giraffe Heart Examined by Stereological Methods: Left Ventricular Morphology of the Giraffe Heart. Anat. Rec. 296(4), 611–621.
  3. Smerup, M., Damkjær, M., Brøndum, E., Baandrup, U. T., Kristiansen, S. B., Nygaard, H., Funder, J., Aalkjær, C., Sauer, C., Buchanan, R., et al. (2016). The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output. J Exp Biol 219(Pt 3), 457–463.
  4. Stenvinkel, P., Shiels, P. G., Painer, J., Miranda, J. J., Natterson-Horowitz, B., Johnson, R. J. (2020) A planetary health perspective for kidney disease. Kidney International, 98(2), 261-5.
  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.
  7. Devinsky, O., Boesch, J., Cerda-Gonzalez, S., Coffey, B., Davis, K., Friedman, D., Hainline, B., Houpt, K., Lieberman, D., Perry, P., Pruss, H., Samuels, M., Small, G., Holger, V., Summerfield, A., Vite, C., Wisniewski, T., and Natterson-Horowitz, B. (2018) Veterinary and Human Disorders Affecting Brain and Behavior. Nature Reviews Neurology, 14(11),  677-86.
  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.
Special Issue of J. Mol. Med on Evolutionary Medicine

Special Issue of J. Mol. Med on Evolutionary Medicine

A special issue of the Journal of Molecular Medicine on Evolutionary Medicine has ten articles of special interest

The editor, Konstantinos Voskarides, says in the overview “Evolutionary Medicine is a fast-growing research field providing biomedical scientists with valuable information on molecular and pathophysiological mechanisms of disease. This is the reason that Journal of Molecular Evolution has devoted this issue to Evolutionary Medicine. Nine detailed review papers are included in this issue, analyzing topics that are among the “hottest” subjects of Evolutionary Medicine. All information is up to date and highly valuable for scientists that would like to start their career or get updated on this field.”

Voskarides, K. (2020). Editorial: A New Bright Era for Evolutionary Medicine. Journal of Molecular Evolution, 88(1), 1–2.

Stearns, S. C. (2020). Frontiers in Molecular Evolutionary Medicine. Journal of Molecular Evolution, 88(1), 3–11.

Byars, S. G., & Voskarides, K. (2020). Antagonistic Pleiotropy in Human Disease. Journal of Molecular Evolution, 88(1), 12–25.

Christaki, E., Marcou, M., & Tofarides, A. (2020). Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence. Journal of Molecular Evolution, 88(1), 26–40.

Daschner, A., & González Fernández, J. (2020). Allergy in an Evolutionary Framework. Journal of Molecular Evolution, 88(1), 66–76.

Kaján, G. L., Doszpoly, A., Tarján, Z. L., Vidovszky, M. Z., & Papp, T. (2020). Virus–Host Coevolution with a Focus on Animal and Human DNA Viruses. Journal of Molecular Evolution, 88(1), 41–56.

Kyriazis, M. (2020). Ageing Throughout History: The Evolution of Human Lifespan. Journal of Molecular Evolution, 88(1), 57–65.

Mourouzis, I., Lavecchia, A. M., & Xinaris, C. (2020). Thyroid Hormone Signalling: From the Dawn of Life to the Bedside. Journal of Molecular Evolution, 88(1), 88–103.

Rocha, J. (2020). The Evolutionary History of Human Skin Pigmentation. Journal of Molecular Evolution, 88(1), 77–87.

Saitou, M., & Gokcumen, O. (2020). An Evolutionary Perspective on the Impact of Genomic Copy Number Variation on Human Health. Journal of Molecular Evolution, 88(1), 104–119.

Club EvMed January: Cancer and Aging

Sign up now for two great Club EvMed discussions in January

Club EvMed: Integrating evolutionary dynamics into clinical cancer treatment

Monday, January 11th at 12pm EST

Join us for a conversation with Robert Gatenby, Co-Director of the Center of Excellence for Evolutionary Therapy and Chair of the Department of Diagnostic Imaging at the Moffitt Cancer Center. In the talk, Dr. Gatenby will outline basic evolutionary principles and mathematical models used to design clinical therapies with the goal of both control and cure of metastatic cancers. He will summarize the results of the first evolution-based clinical trial in metastatic, castrate-resistant prostate cancer. Attendees are encouraged to read Zhang et al. 2017 “Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer,” Stanková et al. 2019 “Optimizing cancer treatment using game theory,” Gatenby and Brown 2020 “Integrating evolutionary dynamics into cancer therapy,” and Gatenby et al. 2019 “First strike-second strike strategies in metastatic cancer: lessons from the evolutionary dynamics of extinction.”

After the talk, perspectives on how the research applies in a clinical setting will be presented by Shelley Hwang, Mary and Deryl Hart Distinguished Professor of Surgery and Chief of Breast Surgery at Duke. Sign up here for the meeting link:–rrjMpG9Nn2VYkmDZAUQgyQmz339QG.

Club EvMed: Successful Aging in the Forest: How wild chimpanzees can help us understand the evolution of human aging

Thursday, January 28th at 12pm EST

Join us for a conversation with Melissa Emery Thompson, Associate Professor of Anthropology at the University of New Mexico. Recent research has revealed that despite shorter life expectancies, humans in small-scale subsistence populations exhibit surprisingly good health, suggesting that some debilitating diseases of aging may be novel products of industrialized environments. This research highlights an urgency to look deeper in our evolutionary past to understand how we age today. I will discuss emerging findings from the first longitudinal study to examine aging in our closest evolutionary relatives, chimpanzees, in their natural environment. Attendees may be interested in reading articles in a recent theme issue on primate agingSign up here for the meeting link:

Maladaptation: Special Issue of Evolutionary Applications

Maladaptation: Special Issue of Evolutionary Applications

Evolutionary Medicine focuses on maladaptation. A special Issue of Evolutionary Applications offers a series of useful papers on the latest thinking. The overview article is likely to be of special interest.

Causes of maladaptation

Steven P. BradyDaniel I. BolnickAmy L. AngertAndrew GonzalezRowan D.H. BarrettErika CrispoAlison M. DerryChristopher G. EckertDylan J. FraserGregor F. Fussmann… See all authors First published: 23 July 2019

Evolutionary biologists tend to approach the study of the natural world within a framework of adaptation, inspired perhaps by the power of natural selection to produce fitness advantages that drive population persistence and biological diversity. In contrast, evolution has rarely been studied through the lens of adaptation’s complement, maladaptation. This contrast is surprising because maladaptation is a prevalent feature of evolution: population trait values are rarely distributed optimally; local populations often have lower fitness than imported ones; populations decline; and local and global extinctions are common. Yet we lack a general framework for understanding maladaptation; for instance in terms of distribution, severity, and dynamics. Similar uncertainties apply to the causes of maladaptation. We suggest that incorporating maladaptation‐based perspectives into evolutionary biology would facilitate better understanding of the natural world. Approaches within a maladaptation framework might be especially profitable in applied evolution contexts – where reductions in fitness are common. Toward advancing a more balanced study of evolution, here we present a conceptual framework describing causes of maladaptation. As the introductory article for a Special Feature on maladaptation, we also summarize the studies in this Issue, highlighting the causes of maladaptation in each study. We hope that our framework and the papers in this Special Issue will help catalyze the study of maladaptation in applied evolution, supporting greater understanding of evolutionary dynamics in our rapidly changing world.

Call for Papers: Evolutionary Medicine & Palaeopathology

Call for Papers: Evolutionary Medicine & Palaeopathology

Evolution Medicine and Public Health will publish a special issue on Paleopathology in 2021. Submissions are invited. See below and this link for details

Bioarchaeology and its sub-discipline palaeopathology provide direct insight into the appearance, prevalence,  manifestations, and impact of particular health problems through thousands of years of human history and  prehistory. As such, these disciplines help to explain how and why certain diseases have emerged and evolved in humans. Additionally, the information gained from these archaeological contexts has the potential to identify possible aetiological factors that can be difficult to see in smaller, more locally confined clinical studies.

Currently, palaeopathology is under-represented in evolutionary medicine. With this in mind, we are launching a Virtual Issue of Evolution, Medicine and Public Health (EMPH) that will address questions in evolutionary medicine from the unique perspective of paleopathological research. 

For this Virtual Issue, we welcome and encourage the submission of data-driven research papers from scholars who use bioarchaeology and evolutionary theory to answer questions about medical issues affecting humans. If you or your lab are conducting such research, please consider submitting a paper to EMPH for consideration.  

Paper submissions will be accepted for consideration for this virutal issue from now until the target date of August 31, 2021.

Please contact the organizers for more information: Kimberly Plomp at,  Gillian Bentley at, or Frank Rühli at