Would it be possible for a recombination event to happen in nature as well? Because I just read that the mice who carry pre-XMRV were used in the US as early as 1930. If I understand correctly you have mice that carry pre-XMRV1 and mice that carry pre-XMRV2. If they breed, couldn't a recombination happen as well? I have no clue (obviously).
Hi Jemal, the short answer to your question is Yes. The long answer is complicated.
My understanding of this was based on a thread on PR mid-late last year. George has studied the history of this. In the early 1930s, at the site of the earliest strongly suspected outbreak of ME in California in 1934, they were investigating a problem called mouse encephalitis. They showed it was transmissible. I ran a search and found a scanned newspaper clipping from the time. It think I might be able to dredge it up, but I would have to rerun a search to find the link.
They also vaccinated some people, I think, but I do not recall well enough to be sure. These people became sick and sued, received a million each in compensation. Could that be how XMRV got into the population?
Pre-XMRV genes seem to be scattered over different mouse species and populations. It could have arisen many times.
However, Coffin et. al. assert that the exact recombination events that gave rise to XMRV are so unlikely that they could not have occurred twice. In addition, the virus appeared in the process of developing a cell line - so it they claim it must have arisen in that cell line. They could be be right about that point.
On the other hand, if contamination is so easy from this virus, and it was pre-existing, it might be that this cell line, which is unusually susceptible to XMRV, might have itself been contaminated.
In addition, the argument that the crossover event could not have happened twice (or three, or a hundred) times is not a strong one in my view. Based purely on math, it does look strong from one perspective - one chance in a very big number that it could happen (I would have to go back to CROI to find that number). However, this calculation presumes a random chance of recombination, which is misleading. It is probably far less than random. This means the probability calculation is flawed, as probability requires equal weight to all possibilities for this kind of calculation.
In my view, recombination events are more likely to occur at specific points in a viral strain genetic sequence. In addition, most recombinations will be flawed and non viable. However, what if there were a dozen recombination events, and those virus recombined several times? What happens to the odds then? Mix and match and genetic drift, together with high viral replication rates and convergent evolution, could have led to XMRV being formed several times in history. There are a lot of mice, and a lot of mammals, in the world. I am not saying this is the case, only that there is room for doubt.
The strongest argument against the lab recombination theory during cell line manufacture causing experiment contamination comes from the data of WPI and other researchers. It should be in all the controls at the same rate. It should be detectable in reagents etc. It has not been found in the reagents, nor in most of the controls.
Bye
Alex