Giraffe has long neck thanks to a set of genes that helped it adapt

Why does the giraffe have such a long neck while its cousin, the okapi, does not? Scientists who sequenced the genomes of the two species say it is down to a small set of genes in the giraffe that showed multiple signs of adaptation, including a long neck and legs so that it could get at those leaves high up in the trees.

Douglas R. Cavener, Professor and Verne M. Willaman Dean, Eberly College of Science at Penn State University, and colleagues from the US, Tansania and the UK, explained in the journal Nature Communications (citation below) that they have, for the first time, sequenced the genomes of the giraffe and the reclusive okapi, its closest living relative.

The sequencing revealed the first clues regarding the genetic changes that led to the evolution of the giraffe’s exceptional height and long neck – the giraffe is the tallest land species in the world.

Giraffe and OkapiAlthough the okapi is the giraffe’s closest living relative, the giraffe has a very different cardiovascular, musculoskeletal and nervous system because of its exceptionally long legs and neck. The okapi looks more like a zebra than a giraffe.

The giraffe – our tallest land animal

Prof. Cavener said:

“The giraffe’s stature, dominated by its long neck and legs and an overall height that can reach 19 feet (~ 6 m), is an extraordinary feat of evolution that has inspired awe and wonder for at least 8,000 years – as far back as the famous rock carvings at Dabous in the Republic of Niger.”

“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.”

The giraffe, for example, has a specially-adapted heart so that it can pump blood two metres straight up to make sure the animal’s brain gets an adequate blood supply. Its heart has an unusually large left ventricle – it also has blood pressure more than double that of other mammals.

To identify the genetic changes that were responsible for the giraffe’s unique features, including sprints that can reach 60 km/h (37 mph), Prof. Cavener and Morris Agaba, of the Nelson Mandela African Institute for Science and Technology in Tanzania, compared the gene-coding sequences of the okapi and the giraffe to over forty other mammals including the goat, sheep, cow, camel and human.

Giraffes vs OkapiThe two genetically-related animals – giraffes and okapi – have some features in common, and many which are unique to each animal.

Okapi and giraffe share relatively recent ancestor

The okapi’s and giraffe’s gene sequence are very similar because they both diverged from a common ancestor approximately 11 to 12 million years ago – which on an evolution timescale is relatively recently.

Despite having a close evolutionary relationship, the okapi has more zebra-like features, and lacks the giraffe’s towering height and amazing cardiovascular abilities.

Precisely for these two reasons, the okapi’s genome sequence provides a powerful screen that the scientists have used to identify some of the unique genetic changes that took place in the giraffe.

Using a series of comparative tests to study the genome sequences of the okapi and the giraffe, the authors discovered seventy genes that showed multiple signs of adaptations.

Prof. Cavener said:

“These adaptations include unique amino-acid-sequence substitutions that are predicted to alter protein function, protein-sequence divergence, and positive natural selection.”

More than half of the seventy genes code for proteins that we know regulate the development and physiology of the cardiovascular, skeletal and nervous systems – exactly the type of genes predicted to be required for driving the development of the giraffe’s unique features.

The co-leaders(Left) Douglas R. Cavener, Professor of Biology, Verne M. Willaman Dean, Eberly College of Science, Pennsylvania State University. (Right) Morris Agaba, Research Chair in Genetics and Genomics, Nelson Mandela African Institution of Science and Technology. (Image:

Many of the genes known to regulate either blood pressure or the cardiovascular system showed multiple signs of adaptation in the giraffe.

Giraffe’s unique features linked to just a few genes

Some of these genes control the development of both the animal’s skeleton and cardiovascular system, suggesting the intriguing possibility that just a small number of genes drove the evolution of the giraffe’s turbocharged cardiovascular system and stature.

Genetic clues to the evolution of the giraffe’s long legs and neck were also discovered. The legs and neck of giraffes have the same number of bones as those of other mammals.

Prof. Cavener said:

“To achieve their extraordinary length, giraffe cervical vertebrae and leg bones have evolved to be greatly extended. At least two genes are required – one gene to specify the region of the skeleton to grow more and another gene to stimulate increased growth.”

Giraffe and Okapi feedingA first impression may make you wonder how the giraffe and okapi could be related. However, when you watch them feeding, the similarity becomes evident.

Among the seventy genes that the study revealed are quite different in the giraffe, they identified genes that are known to regulate the development of the legs and neck.

Prof. Caverner added:

“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.”

This fibroblast-growth-factor pathway plays a key role in regulating development, starting in early development at the embryo stage, and extending through the bond-growth phase after the baby giraffe is born.

In mice, and also in humans, severe cardiovascular and skeletal defects are linked to debilitating mutations in this gene.

The authors said they also identified four homeobox genes – the type involved in the development of body structures. These are known to specify the regions of the legs and spine.

Prof. Cavener speculates:

“The combination of changes in these homeobox genes and the FGFRL1 gene might provide two of the required ingredients for the evolution of the giraffe’s long neck and legs.”

Dr. Agaba first noticed a set of genes regulating growth and metabolism that were diverged in the giraffe as compared to the okapi. One of these genes encodes the folic acid receptor. Folic acid is an essential B vitamin required for normal growth and development.

Among other metabolic genes found to be considerably changed in the giraffe are those involved in the metabolism of the volatile fatty acids that are generated by the fermentation of ingested plants – a major source of energy for ruminants, including cattle, goats and giraffes.

Part of giraffe’s diet toxic to other animals

The giraffe has a unique diet consisting of seedpods and acacia leaves, which are very nutritious but toxic to other animals. The authors speculate that the genes responsible for metabolizing acacia leaves may have evolved in the giraffe in order to overcome this toxicity.

Dr. Agaba and Prof. Cavener, both experimental geneticists, would like to test the function of some of the genes that they think could be responsible for the giraffe’s unique features.

They and their colleagues are currently testing the potential effect of the unique differences of the giraffe’s FGFRL 1 gene by introducing these changes into laboratory mice, using state-of-the-art CRISPR gene-editing methods.

By substituting the giraffe’s FGFRL1 gene into a mouse, they do not expect to end up with a long-necked mouse. They are hoping to determine how the giraffe’s FGFRL1 gene may affect differential growth of the legs and spine of a mouse that is predictive of the giraffe’s unique characteristics.

Prof. Cavener said:

“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.”

“While the plight of the elephant — giraffe’s shorter companion in the African savannah — has received the lions share of attention, giraffe populations have declined by 40 percent over the past 15 years due to poaching and habitat loss.”

“At this 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.”

The study was funded by Penn State, the Nelson Mandela African Institute for Science and Technology, and Penn State’s Huck Institutes of the Life Sciences.

In an Abstract in the journal, the scientists wrote:

“Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions.”

Citation: Giraffe genome sequence reveals clues to its unique morphology and physiology,” Brendan Wood, Heather Robertson, Morris Agaba, Edson Ishengoma, Webb C. Miller, Craig A. Praul, Lan Wu-Cavener, Barbara C. McGrath, Chelsea N. Hudson, Oscar C. Bedoya Reina, Rayan Chikhi, Paul Medvedev, Aakrosh Ratan, Rico Burhans, Linda Penfold & Douglas R. Cavener. Nature Communications 7, Article number: 11519. 17 May 2016. DOI: 10.1038/ncomms11519.

Video – Giraffe’s long neck thanks to a few genes

The only thing that separates the towering giraffe from its smaller cousin – the okapi – is a handful of genes.