Dying Dolphins and Dead Genes

The Atlantic bottlenose dolphin is one of several toothed whale species which have suffered in recent outbreaks of viral diseases. Can their susceptibility to novel diseases be explained by ancient mutations in two important genes?

Marine environments tend to be the hardest places to study disease outbreaks: The ocean is immense and deep, animals are dispersed few and far between, not to mention the expensive equipment you’d need just to get to your study site. But with human activity having literal downstream effects on the health of organisms and ecosystems in the open ocean, encouraging the emergence of novel diseases like sea star wasting disease, aspergillosis on sea-fans, and toxoplasmosis in sea otters, it is now just as imperative to understand the susceptibility of marine organisms to disease as their terrestrial counterparts.

One recent outbreak of an emerging disease in the mid-Atlantic is caused by cetacean morbilliviruses (CMVs), a collection of paramyxoviruses implicated in mass die-offs of dolphins, porpoises, and other toothed whales. The disease is characterized by open wounds in the skin and lungs, as well as brain infections and suppressed immune function, and can be transmitted via direct contact between animals or aerosolization and inhalation of virus particles. Morbilliviruses are causes of well-known diseases in humans and other terrestrial mammals, such as measles, rinderpest, and canine distemper. To combat these diseases, two mammalian genes, Mx1 and Mx2, encode proteins involved in defense against paramyxoviruses and other virus strains. Mutations in certain regions of these genes can render those proteins nonfunctional and open an animal to infection.

To predict how whales might deal with exposure to these viruses, Benjamin A. Braun and his colleagues at Stanford University set out to compare the Mx1 and Mx2 gene sequences of five whales with those of cows and humans. Extant whale species are classified into two groups that shared a common ancestor: the Mysticeti, the baleen whales, and the Odontoceti, the toothed whales, porpoises, and dolphins. They found that Mx1 and Mx2 in the minke whale, a baleen whale, were intact and comparable to those of humans and cows, as would be expected for genes maintained under selective pressure to protect an animal from viral infection. However, all four toothed whales they tested (sperm whale, baiji, orca, and bottlenose dolphin) displayed extensive mutations throughout both Mx1 and Mx2, including in regions that, when mutated in humans and mice, cause the genes to lose their function. And not only have the genes lost their function, but the whales have also completely stopped making the proteins from these genes altogether. Because some of these loss-of-function mutations were shared by all four toothed whales, Braun and colleagues concluded that all of the toothed whales may have lost their functional Mx1 and Mx2 as far back as their common ancestor, 33-37 million years ago.

Mx1 and Mx2 genes in toothed whales show extensive areas that have been deleted, cut short, or code for entirely different amino acid residues (red areas) compared to humans and even baleen whales. For comparison, other mutations in the Mx1 gene in humans and mice lead to the loss of function of Mx1, suggesting that the Mx1 genes of all toothed whales have also lost their original functions during the course of evolution. From Braun et al. (2015).

What might have been the evolutionary impetus for this unprecedented loss of function for such important genes? The researchers speculate that such a mutation could not have occurred and persisted for millions of years without some important advantage being conferred by not having these genes, such as protection from a hypothetical pathogen that, rather than being warded off by Mx1 & Mx2, might have used those proteins to facilitate infection. But could this also render toothed whales and dolphins susceptible to novel viruses like CMVs in a changing ocean? An interesting direction in which this finding may be taken might be to understand how, or if, toothed whales fend off CMVs and other viruses compared to other marine mammals. With many ocean species continuing to face new as well as old challenges to their survival, understanding the ecological, evolutionary, and physiological bases of disease in marine environments will allow us to incorporate a better understanding of marine disease dynamics into conservation.

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