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Study shows toothed whales have persisted millions of years without two common antiviral proteins

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Our ability to fend off the flu, HIV and other viruses is enhanced when proteins are produced by two "immune genes," called MX1 and MX2. Other mammals also have these genes, but little is known about the role they play in the immune responses of these animals.

Now a study comparing the genomes and Mx genes of 60 mammal species has revealed a surprising finding: Every species in the study has functioning Mx1 and Mx2 genes except for dolphins, whales and orcas — species from a lineage of toothed whales that's persisted for roughly 33 million years.

Gill Bejerano, PhD, a geneticist and developmental biologist, graduate student Benjamin Braun and their team wanted to know more about the status and function of Mx genes in non-human mammals. To do this, they examined and compared the part of the genome that contains the Mx genes in 60 different species including humans, cows, whales, dolphins and orcas.

I think this will open up very exciting research avenues, either to better protect the compromised whales, or to study their different viral defenses, and someday add them to our own arsenal.

The study, published this week in the Proceedings of National Sciences, showed that the Mx1 and Mx2 genes in the toothed whales (bottlenose dolphin, orca, Yangtze river dolphin and sperm whale) they tested were non-functional, and couldn't produce the proteins that help fight viral infections. Bejerano explained the significance of this finding in our press release:

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.

To find out when in evolutionary history these genes became inactive the researchers compared the genomes of toothed whales to that of their closest ancestors, the baleen whales and hoofed mammals (ungulates). They found that the Mx genes function in baleen whales and hoofed mammals, but not in toothed whales. This means that some — perhaps all — toothed whales likely lost use of their Mx genes when this lineage split off from these ancestors about 33 million years ago (see Fig. 1).

Why these two genes became inactive or how the toothed whales have survived so long without the use of these two viral-fighting genes is not yet understood. In their paper, the authors describe a possible scenario where toothed whales may have suffered from a viral outbreak millions of years ago that exploited the Mx genes. This, they say, may have forced ancestral toothed whales to sacrifice the use of both Mx genes.

The authors also point out that although the toothed whales have persisted for millions of years, they are plagued by viral infections such as the recent mass stranding of about 1,000 bottlenose dolphins that was attributed to cetacean morbillivirus.

"It’s likely that the toothed whales’ immune system is very different from ours," Bejerano said. "I think this will open up very exciting research avenues, either to better protect the compromised whales, or to study their different viral defenses, and someday add them to our own arsenal. We’re putting the genomic discovery out there, and we hope immunologists will follow up on it."

Previously: Study: Chimps teach people a thing or two about HIV resistanceZebrafish: A must-have for biomedical labsEngineering immune cells to resist HIV and Hey guys, sometimes less really is more
Photo by Karen

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