What is the origin of MS?
A couple of years ago we had the suggestion that the main gene associated with MS was HLA-DR*1501 was selected in sheep herders possible because it protected them from infections in the animals (Zoonosis) and these people from the Steppes migrated Northward and Eastward and this is why this gene is common in Northern Europeans.
Was it the protection from infection that kept the gene common and this was exploited by something that triggered MS?
Or was it that the immune response to infections such as parasitic worm infection lead to overactive responses when the the worm infections dropped.
I guess evidence is one of the features that help shape your ideas is fact and the “Hygiene hypothesis” (Old friends) whereby the fact that we are infectiously cleaner now rather than yester year leaves us vulnerable to autoimmunity. The old friends idea was tested and has largely been put to the sword when people were infected with parasitic worms and their MS didn’t go away. So the old friends idea takes a dent. However was this the right experiment to show this? I doubt it because if you do studies in MS what is important has already happened.
If we bring EBV into the equation it is not that simple. EBV has co-evolved with humans for many many years and what we know is that it is not infection that is important in MS it is when when is key and infection early in life is less associated with autoimmunity than later life autoimmunity. EBV has evolved to get into B cells and the presence of HLA-DR*1501 makes that easier. This makes B cells becomes memory B cells and therefore they can act against targets quickly without every seeing their intended target. This is advantagous for fighting new infections but at the consequence of autoimmunity. These are often later in life events after childbirth and perhaps the advantages outweigh the disadvantages of autoimmunity and in some cases cancer when B cells are activated to be immortal.
In the concept of evolution we have parallell evolution where you get to the same feature via a different evolutionary route. Mammals learned to fly i.e. bats and reptiles learned to fly pterdydactls and created birds. I know this is not the best example…Maybe Gene Simmons and a Giraffe both have enormous toungues:-) Why?.
However, there is alot of MS in the South and this is in Sardinia there there is MS and type I diabetes and here the genetic association is not HLA-DRB115:01 but DRB1 04:05-DQB1*03:01 and the drivers have not suggested to be sheep but mosquitos and malaria.
However infections shape our evolution and response to plague was a good example, it killed a large part of the population, it selected a gene that was later exploited by HIV. All good stuff but very hard to prove
Barrie W. The evolutionary origins of multiple sclerosis. Rev Neurol (Paris). 2026 Apr 1:S0035-3787(26)00496-0. doi: 10.1016/j.neurol.2026.03.004.
There are two main evolutionary theories for why modern humans develop multiple sclerosis (MS). The first, antagonistic pleiotropy, argues that genetic variants that predispose people to MS are protective against infections; this explains why these genetic variants persist at high frequency. The second, the Old Friends hypothesis, argues that reduced exposure to ancient, co-evolved micro-organisms like helminths results in immune dysregulation and overreactions to harmless infections and substances; this explains why MS prevalence increases with sanitation. Here, I assess these theories in the light of recent ancient DNA (aDNA) studies. These suggest that populations from the Pontic-Caspian Steppe which migrated across Eurasia in the Bronze Age evolved a strong pro-inflammatory immune response due to increased zoonotic infections resulting from their pastoralist lifestyle. It is possible that this may have occurred in a context of high levels of anti-inflammatory helminth infections, which resulted in a balanced pro- and anti- inflammatory response. In the modern sanitary world, with a lower helminth burden, the immune system ‘overshoots’ the level of inflammation required. This explains why genetic risk for MS is higher in northern Europe where people have higher genetic ancestry from the ancient Steppe population, and why disease penetrance is increasing.
Source: multiple-sclerosis-research.org