Down (Under) The Rabbit Hole

Maybe it’s a wild guess, but most of us have probably learned a little more about viruses lately than we thought we ever would. Little did I know, before this article, that I’d also learn quite a bit about a 3,256 km long network of fences constructed in the early 1900’s and why you can bring it up in the same breath as…(did you guess?)….viruses.  

Let’s start with rabbits and their favorite continent: Australia. Rabbits were first brought to Australia for meat in the late 1700’s and were generally contained on farms. However, European rabbits were released in 1859 to be hunted for sport. It took them no time flat to do what they do best, and they quickly became well established (more info here). Within ~10 years they reached astronomical numbers and completely devastated crops and pastures, leading to soil erosion and threatening native plants with extinction. In just 50 years they colonized 2/3 of Australia… wow and yikes at the same time.

To control the rabbits, fences were constructed. The most famous of which was the Rabbit Proof Fence (RPF), now called the State Barrier Fence, which helps control other critters including kangaroos, emus and wild dogs in addition to rabbits. While the RPF was actually a series of three fences connected, when RPF No. 1 was completed in 1907, it stretched 1,824 km, and was the longest unbroken fence in the world. By the way, Australia has a lot of fences, if you want more info on the incredibly long (5,614 km) rabbit-turned Dingo (or Dog) Fence, here you go. Even with the fences, by the late 1940’s there were an estimated 600 million rabbits running wild in Australia.

The damage the rabbits inflicted required drastic measures be taken, so in 1950 the myxoma virus was released to control the rabbit population, which it did…until it didn’t. This virus was initially discovered in Uruguay in a lab in 1896 and ended up killing over 99% of infected rabbits when first introduced. The rabbits managed to evade extermination, and the initial lethality did not last forever, especially in areas without mosquitos (the main route of transmission). As Peter Kerr stated in this article: “Thus, inadvertently, began one of the great experiments in natural selection, conducted on a continental scale”. As a side note, Kerr and colleagues actually collected virus samples over multiple decades and tested how the virus impact differed on rabbits over time.

While the myxoma virus was still deadly (just not as effective) in the 1990s, Australia tested another way to control rabbits: rabbit hemorrhagic disease (RHD). RHD is caused by an RNA virus and that is the virus studied in the article for today, whew we finally got there. RHD has hit a different equilibrium among rabbit populations than the myxoma virus, probably partly because it benefits from killing the host as there is a lot of virus present at death, which can then be transmitted via flies to other rabbits. 

This study revolving around the arms race between virus and rabbit, was led by Nina Schwensow.  The authors looked at genetic adaptations in rabbits that might have led to increased resistance to the RHD virus. Previous research suggested that…it’s complicated. Schwensow and colleagues point out some studies where this type of evolution is researched in lab models, but note that in the lab you’re removing a lot of what might be going on in the environment. 

Emerging infectious diseases, as well as what they call “biocontrol” – defined as pest biological control programs – both provide ways to study this so called “arms race”. In this study, the authors looked at genome-wide single nucleotide polymorphisms (SNPs) to assess allele frequency changes in a rabbit population that was first sampled in 1996 and then 16 years later in 2012, which they estimate to be something like 15 to 16 rabbit generations.

They found 19 thousand SNPs in total, with 46 with allele/genotype frequencies that were notably different. The majority of SNPs were located near 57 known genes, that include functions that you might expect, like those involved in antiviral immune responses, apoptosis and other disease responses. They did simulations of what would happen in the population given drift alone, and it wasn’t enough to explain the results. They also incorporated previous data from another study on a different rabbit population, and found a group of significant SNPs were shared, lending some insight into population differentiation.

Ultimately, the authors identified multiple genes likely under RHD virus driven selection, some of which were previously thought to be involved in resistance. There are a lot of variables in this study system, the authors note that a previous virus was introduced decades before RHD, and other natural disasters (like droughts) have also impacted rabbit populations. They emphasize that their results could be linked to the myxoma-rabbit coevolution or genes broadly involved in generic resistance to pathogens.

This is a very unique study system, in which an experiment that could provide continually different insight to understanding the coevolution of both rabbit and virus is being carried out on a continental scale. Schwensow et al. also noted that a new serotype of the RHD virus was identified in 2014, which seems to infect younger rabbits and have unique properties, so it sounds like there is yet more work to be done. Time for another rabbit hole.

Study Reference:

Schwensow, N., Pederson, S., Peacock, D., Cooke, B. and Cassey, P., 2020. Adaptive changes in the genomes of wild rabbits after 16 years of viral epidemics. Molecular Ecology. https://doi.org/10.1111/mec.15498

Assorted additional articles:

About Kelle Freel

I'm currently a postdoc working at the Hawai'i Institute of Marine Biology with Dr. Mike Rappé. I'm interested in the biogeography and ecology of microbes, especially of the marine variety. After studying a unique genus of marine bacteria at Scripps Oceanography in grad school, I moved to France, where I worked with a group studying yeast population genomics. In my free time, I like to do outdoorsy stuff, travel, and cook.
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