Variola virus evolution

Why do some people get severely ill with an infection while others catch the same virus but don’t get sick? There are many factors that can influence the progression and outcome of disease, but they can be lumped into four basic categories: host, agent, transmission and environment. For example, infection with Variola virus results in smallpox, but case fatality rates in different outbreaks range from very low to as high as 30%. Its likely that many factors contribute to this variability, but it’s likely that differences in viral strains is one of them.

Summers are quiet here at Vassar. There are no summer classes but we do have a program to support undergraduate research (“URSI”) so that students can gain some research experience and professors can get cheap labor. This summer I had a student working with me who is a Biochemistry major and Computer Science minor (called a “correlate” here). She can write code and I cant, so I had her working on a bioinformatics project. We were interested in investigating the difference between poxviruses that cause high mortality rates in humans (like some strains of Monkeypox virus and most strains of Variola virus) and those that dont. I recently published a paper along with another undergraduate student showing that certain genes in poxviruses are under Darwinian selective pressure. We wanted to test the hypothesis that the selective pressure differs between virulent and avirulent strains. She used several approaches involving analysis of synonymous and non-synonymous mutation rates to see if amino acid altering mutations were fixed at different rates in virulent and avirulent viruses.

As she crunched away at code writing and data analysis and discovered one of the joys(?) of science: failing to support your hypothesis. We could not find evidence that selective pressure differed between virulent and avirulent strains. Although no Vassar student wants to fail, failing to support a hypothesis is not actually failure. Rather, its an integral part of the scientific process, something that comes from the successful execution of an experiment that tests your hypothesis. The scientific method is actually quite humbling: you set up experiments that will tell you if you are wrong, and as a scientist, you have to get used to proving yourself wrong.

So now we must ask a new question: since some poxvirus genes show evidence of selective pressure, and that selection is not related to virulence, what is the cause of that pressure?