The evolutionary origins of multiple sclerosis

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.