Researchers at the Stanford University School of Medicine have determined that toothed whales lack functional Mx genes — a surprising discovery, since all 56 other sequenced mammals in the study possess these genes to fight off viruses like HIV, measles and flu.

Modern toothed whales, including dolphins, orcas and sperm whales, have inherited defunct copies of the Mx1 and Mx2 genes, profoundly altering their immune systems. The basic role of these Mx genes is to make proteins that fight viral infections. The researchers hope that understanding this newly discovered mysterious genetic anomaly will help preserve these cetaceans as they face extensive die-offs.

“Given how important the Mx genes seem to be in fighting off disease in humans and other mammals, it’s striking to see a species lose them both and go about its business for millions of years,” said Gill Bejerano, PhD, associate professor of developmental biology, of computer science and of pediatrics. “It’s hard to determine if this is related to the die-offs. We hope that our observations will provide particular targets to go after when carcasses wash ashore, so we can better understand what is happening.”

Bejerano is the senior author of a paper, published online June 15 in the Proceedings of the National Academy of Sciences, that describes the work. The lead author is graduate student Benjamin Braun.

Double-pronged strategy

Bejerano said his lab team began investigating Mx genes because, in primates, they are engaged in an arms race against rapidly evolving viral proteins. In order to determine the state of the Mx genes in mammals, he and his colleagues compared the genomes of 60 mammals.

“We compared the whole-genome sequence of four toothed whales, a baleen whale and dozens of related mammals like cows and humans,” said Bejerano. “When we looked carefully at the genome sequences, it was very clear that the Mx genes are completely messed up only in the toothed whales.”