By Margaret Evans

Recently, an international team of scientists decoded the genome of the domestic horse Equus caballus and the results, published in the journal Science, showed a genome structure remarkably similar to humans. The research was led by scientists at the Broad Institute of MIT and Harvard, a collaboration of Massachusetts Institute of Technology and Harvard University, in conjunction with an international group from 11 countries that all came together on the Horse Genome Project, which actually began in 1995.

The researchers analyzed DNA from an adult Thoroughbred mare called Twilight from Cornell University in Ithaca, New York. The subsequent genome revealed a sequence that is roughly 2.7 billion letters, or nucleotides, in size, larger than the dog genome but smaller than the human or cow genomes.

In addition to Twilight, they also analyzed DNA from other breeds including the Quarter Horse, Andalusian, Arabian, Belgian draft horse, Hanoverian, Hokkaido, Icelandic, Norwegian Fjord, and Standardbred, as well as the wild Przewalski’s horse.

“Basically you could not separate the Przewalski’s horse from any other breed,” said Dr. Claire Wade, formerly with the Broad Institute and now with the Faculty of Veterinary Sciences, University of Sydney, Australia. “We (also) used three horse breeds from Japan and the Akhal-Teke breed from the Middle East, which was the most diverged. We sampled a donkey (which) has its own variants. Ancestrally the donkey has its own branch of the (equid) family tree whereas the Przewalski’s horse does not.”

The team examined genetic variations both within breeds and across different breeds to create a catalogue of more than one million tiny single-letter genetic differences. These slight changes are known as “single nucleotide polymorphisms” or SNPs. The team then isolated specific gene mutations and mapped the horse’s DNA profile to show exactly where these certain traits were centered.

This promises to be significant for both humans and horses because of another discovery. During evolution, parts of chromosomes can change location; or, like beads on a string, they can remain in their ancestral order, a structure called “synteny.”

Humans and horses are much closer than we previously thought, according to our genes. Photo: Robin Duncan Photography

According to the Broad Institute’s Research News by Nicole Davis, the fascinating thing about the horse genome is the small number of chromosomal rearrangements that have occurred in horses relative to humans. In fact, the researchers discovered that 53 percent of horse chromosome pairs showed synteny with a human chromosome. By comparison, only 29 percent of dog chromosomes show the same synteny. This indicates that there are fewer chromosomal rearrangements separating horses from humans than separating humans from dogs.

Perhaps it is this genetic similarity that explains why horses suffer from more than 90 hereditary diseases similar to those in humans, including conditions such as infertility, inflammatory diseases, respiratory and allergic diseases, and muscle disorders.

“Horses and humans suffer from similar illnesses, so identifying the genetic culprits in horses promises to deepen our knowledge of diseases in both (horse and human) organisms,” said senior author Kerstin Lindblad-Toh with the Broad Institute and a professor of comparative genomics at Uppsala University, Sweden.

For instance, the researchers used the SNP catalogue to localize the gene mutation in the leopard complex or the unique spots on Appaloosa horses. Horses with a specific colour trait variation may suffer from a form of night blindness which is also a human disorder. They narrowed the genetic suspects for night blindness to 42 associated SNPs including two mutations located near a gene involved in skin pigmentation.

The genome results may also help with respiratory issues such as airway obstructions in horses and asthma in humans as well as osteochondrosis, a joint disorder that can affect horses, dogs, and children.

If the similarity between the chromosomes of horses and humans wasn’t exciting enough, researchers became really curious about a little understood thing on a chromosome called a “centromere.” A chromosome is shaped like a wavy X. The centromere is located where the arms cross and it is a key structural feature necessary for the movement of a chromosome when cells divide. Not much is known about centromeres except that they contain highly repetitive DNA sequences. When cells divide, centromeres ensure that the “daughter” cells inherit exact copies of each chromosome and the DNA sequences. So imagine how surprised scientists were to find that on chromosome 11 in the horse, there was a developing centromere, frozen in time, with no repetitive DNA. It answered one enduring question (for folks who do this stuff): centromeres appear on a chromosome before the DNA sequencing. But it also begged answers to a fascinating question: just what does this new centromere without any DNA sequencing mean to the evolutionary future of the horse?

“The centromere on chromosome 11 is located differently,” said Wade. “We always thought that a centromere had to have DNA around it. But on this chromosome of the horse it did not have the satellite.”

Does this shift from the status quo show an evolutionary process in action in the horse that has not been seen before?

Access to multiple genome sequences makes it easier for scientists from many disciplines to understand all genomes. By looking at the horse genome there will be better understanding of human biology and human diseases, and of our evolutionary connectedness.

Horses were first domesticated some 5000 to 6000 years ago and from the genome study it was clear that the passage to domestication was smooth. From mitochondrial DNA studies done at Uppsala University, Sweden, it was discovered that the first domesticated horses were all mares. From separate studies done by the University of Exeter, UK, there is clear evidence from pottery shards that the horses were also milked, a practice that continues today in Kazakhstan.

Clearly our companionship with the horse has been enjoyed for millennia. And as illustrated by the newly revealed genome, we’re much closer to our horses than we think.

Main photo: Doug Antczak, College of Veterinary Medicine, Cornell University, New York - Researchers have sequenced the equine genome using DNA from Twilight (shown), a Thoroughbred mare from Cornell University in Ithaca, New York.