The giraffe is the tallest extant terrestrial animal, and its iconic long neck (6 feet) provides advantages for foraging for food and detecting predators on the veldt over long distances. As a consequence, however, the giraffe has a blood pressure two-fold higher than other ruminant animals needed to bring blood to the brain that is so far away from the animal's heart.

An earlier (2016) study of giraffe genome and genome of the related okapi (Okapia johnstoni) was not optimal, being restricted to 17,210 genes identified by comparison to cattle (Bos taurus) genome. Last Wednesday, a team of Chinese and Norse scientists published a paper entitled "A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe," in Science Advances. In this paper, the authors described their work on Rothschild's giraffe (Giraffa camelopardalis rothschildi), which provided a higher "completeness" for this genome than previous studies. The analysis provided the sequence of a 2.44 Gb assembly covering about 98% of giraffe genomic DNA. Using comparisons with genomic DNA of cattle, goat, and okapi (with sperm whale as "outgroup"), the authors reported an assemblage of a putative common ancestor between giraffe and cattle; this resulted in a prediction of an evolutionary history of 4 chromosome fissions and 17 fusions that has resulted in the 15 haploid chromosome complement of modern giraffes (albeit admitting the need for further analysis to understand the significance of this result).

In this chromosomal complement these researchers discerned 101 genes under positive selection and 359 undergoing "rapid evolution," related to growth and development, nervous and visual systems, circadian rhythm, and blood pressure regulation. One gene in particular was the focus this research: the giraffe fibroblast growth factor receptor-like protein 1 (FGFRL1) gene was found to have seven non-synonymous mutations affecting the FGF binding domain, the most in any genetic sequence comparison to other ruminant mammals. This gene was known to be involved in bone mineral density and hypertension resistance (thought to permit blood flow to the heights the giraffe's neck requires). To investigate the relevance of these mutations to giraffe physiology, the researchers used CRISPR-Cas9 to introduce these mutations into the mouse FGFRL1 gene. The resulting phenotype in these mice was found to be resistant to treatment with a high blood pressure-inducing drug (angiotensin II) while showing no developmental changes in cardiac structure; wildtype mice showed "significantly increased blood pressure" as a result of drug treatment. These genetically altered mice also displayed significantly higher bone density as adults, with skeletal hypoplasia immediately postnatally. Otherwise no deleterious effects were noted in these mice. Together these results suggested these mutations could be responsible, at least in part, for the giraffe's characteristic long-necked phenotype.

This genetic research also detected differences in genes involving cardiac development, blood vessel characteristics and increased glomerular filtration rate in giraffe kidney, as well as genes involved in platelet function (including the phosphatidylinositol metabolism genes PIP4K2A, ISYNA1, MTMR3, CDS1, and INPP1) and ion transport related to cardiac contraction.

With regard to genetic adaptation of sensory genes (important for an herbivorous ungulate subject to predation by, inter alia, lions), these researchers found differences in genes related to eye development, vision, hearing, and balance. Like other ruminants, giraffes have only two opsin genes, suggesting the absence of trichromatic color vision. Perhaps curiously, the giraffe genome has lost 53 olfactory-related genes compared with the opaki, due to segmental deletion of sets of genes spatially clustered in the opaki genome, which these researchers speculated was a sensory "tradeoff" with their increased visual acuity.

Giraffes are known to have sleep durations among the lowest of all mammals. Consistent with this phenotype circadian rhythm genes are altered in giraffes, particularly having a translation stop codon in the PER1 gene involved in circadian rhythm maintenance.

These researchers conclude their paper saying:

Overall, these results show that pleiotropy is a plausible mechanism for contributing to the suite of co-adaptations necessary in the evolution of the giraffe's towering stature. However, because of the complexity of cardiovascular and sensory systems, more research on the functional consequences of giraffe-specific genetic variants is needed.

* School of Ecology and Environment, Northwestern Polytechnical University, Xi'an, China; Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, China; College of Animal Science and Technology, Jilin Agricultural University, Changchun, China. BGI-Qingdao, BGI-Shenzhen, Qingdao, China; Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Xi'an, China; Jiaxing SynBioLab. Co. Ltd., Jiaxing, China; Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China; Center for Evolutionary Hologenomics, GLOBE Institute, University of Copenhagen, Øster Voldgade, Copenhagen, Denmark; Norwegian University of Science and Technology, University Museum, 7491 Trondheim, Norway; Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.

Image of Rothschild's giraffe (Giraffa camelopardalis rothschildi) at Murchison Falls NP, UGANDA by Bernard DUPONT, from the Wikimedia Commons under the Creative Commons Attribution-ShareAlike 2.0 Generic license.