Skip to main content
Premium Trial:

Request an Annual Quote

Giraffe, Okapi Genomes Reveal Clues to Height, Other Differences

NEW YORK (GenomeWeb) – An international research team has sequenced the genomes of two Masai giraffes, Giraffa camelopardalis tippelskirchi, and one okapi, Okapia johnstoni, in order to unravel some of the secrets behind the giraffe's unique features.

"The evolutionary changes required to build the giraffe's imposing structure and to equip it with the necessary modifications for its high-speed sprinting and powerful cardiovascular functions have remained a source of scientific mystery since the 1800s, when Charles Darwin first puzzled over the giraffe's evolutionary origins," senior author Douglas Cavener, a biology professor at the Eberly College of Science at the Pennsylvania State University, said in a statement. 

Cavener's team, which included researchers from Tanzania, Kenya, the US, and the UK, published its findings in Nature Communications this week.

The okapi and the giraffe are the only living members of the family Giraffidae, a group of four-legged mammals that share a common ancestor with deer and bovids, or cloven-hoofed mammals such as domestic cattle. These two animals are related and share some common features, including long dark tongues and horns covered in skin called ossicones. But the giraffe has a unique physiology.

There are seven known subspecies of giraffes, including the Masai giraffe. The animals have evolved a cardiovascular system, musculoskeletal system, and nervous system that can handle the burden their unique body shape demands. Researchers believe that gaining an understanding of how giraffes have evolved to overcome these physiological challenges and structural problems could give insight into new treatments or solutions for cardiovascular disease and hypertension in humans.

They also believe that gaining a better understanding of how these two related animals evolved to have such different features will aid researchers in their understanding of hoofed animal evolution in general, and how to conserve the species.

The team collected DNA samples from two female Masai giraffes and one fetal male okapi and constructed pair-ended libraries with the Illumina TruSeq DNA PCR-Free library preparation kit. They sequenced the samples on an Illumina HiSeq platform, and aligned initial sequence reads to 19,030 cattle reference transcripts in order to predict homologous genes. This approach yielded 17,210 giraffe genes and 17,048 okapi genes.

They performed comparative genome analysis between giraffe, okapi, and cattle genes and found that 19.4 percent of giraffe and okapi proteins are identical. "Okapi's gene sequences are very similar to the giraffe's because the okapi and giraffe diverged from a common ancestor only 11-to-12 million years ago — relatively recently on an evolution timescale," Cavener said in the statement. "In spite of this close evolutionary relationship, the okapi looks more like a zebra and it lacks the giraffe's imposing height and impressive cardiovascular capabilities. For these two reasons, Okapi's genome sequence provides a powerful screen that we have used to identify some of the giraffe's unique genetic changes."

Based on their analysis, the researchers determined that 70 genes displayed multiple signs of adaptation (MSA) in the giraffe genome, including amino-acid sequence substitutions that may alter protein function, protein-sequence divergence, and positive natural selection.

But the researchers also identified genes that specifically regulated both skeletal and cardiovascular development, particularly genes in the HOX, NOTCH, and FGF signaling pathways. One of those genes, HOXB13, regulates angiogenic and posterior axial skeletal development and shows high amino acid sequence divergence in giraffe and okapi genomes compared with other mammals.

"The most intriguing of these genes is FGFRL1, which has a cluster of amino acid substitutions unique to giraffe that are located in the part of the protein that binds fibroblast growth factors — a family of regulators involved in regulating many processes including embryo development," Cavener said.

The team also noted that there were MSA genes in the giraffe genome involved in the catabolism of volatile fatty acids, such as butyrate — MCT1, ACSM3, and ACADS — or downstream oxidative phosphorylation that generates adenosine triphosphate — NDUB2 and SDHB. The researchers believe that these adaptations might explain how the giraffe is able to feed on acacia leaves, which are toxic.

Cavener and his colleague Morris Agaba — a researcher at the Nelson Mandela African Institute for Science and Technology in Tanzania and the paper’s first author — added in the statement that their team is currently testing the potential effect of the unique differences of the giraffe's FGFRL1 gene by introducing these changes into mice using CRISPR gene-editing methods. While they don't expect this substitution to result in a long-necked mouse, the researchers are hoping to see how the giraffe's FGFRL1 gene may affect differential growth of the spine and legs of the mice.

"We hope that the publication of the giraffe genome and clues to its unique biology will draw attention to this species in light of the recent precipitous decline in giraffe populations," Cavener said. "At [the current] rate of decline, the number of giraffes in the wild will fall below 10,000 by the end of this century. Some giraffe subspecies already are teetering on the edge of extinction."