Keeping up with the Red Queen: Co-evolution of hosts and pathogens

While most micro-organisms are harmless to humans, and in some cases even beneficial, there are those that are not welcome. These are known as pathogens, from the Greek for ‘producer of suffering’. For us, pathogens can be very damaging and even deadly, and so we have evolved ways to resist their attacks. For the pathogen, infecting a human might be the only chance to survive and reproduce. The potential reward is so great that pathogens will develop ways around our defences. This becomes an ongoing battle and means that neither side can stop evolving in case the opponent becomes too dominant; in the words of the Red Queen from Lewis Carroll’s Through the Looking-Glass: “It takes all the running you can do, to keep in the same place.” This interplay between host and pathogen is known as co-evolution and can lead to very different strategies being used on both sides.

The Red Queen (not to be confused with the Queen of Hearts) and Alice

All-out war

Aggressive strategies, like that used by the malarial parasite Plasmodium falciparum, can drive co-evolution rapidly. Once it has infected a person, the pathogen replicates as quickly as possible. This is risky because it seriously affects the infected human and can even cause death, and if the host dies, the pathogen die with it. This strategy works because P. falciparum spreads between humans via mosquitoes. High concentration of the parasite in the bloodstream is the best way to ensure that they are taken up by a mosquito and passed on to a new host. However, the severity of malaria and the high likelihood of death means there is a strong evolutionary pressure for humans to develop resistance, even if that comes at a price.

Indeed resistance has developed, via a specific mutation in the gene coding for the blood protein haemoglobin. Everyone has two copies of the haemoglobin gene – one from each parent. A mutation in both copies of the gene provides malarial resistance but causes sickle cell anaemia. This causes blood flow to be restricted and eventually leads to premature death, which obviously outweigh any benefits. Fortunately, having just one copy of the mutation maintains some resistance and avoids sickle cell anaemia. However it can never be guaranteed that a child will inherit exactly one copy of the mutated gene, so there is always a risk of children being born with sickle cell anaemia. This means that the level of the mutation present in the population is determined by the balance between the risk of malaria and the risk of sickle cell anaemia. There is little risk of malaria in the UK and so the mutation is rare. In sub-Saharan Africa, where malaria causes a quarter of all deaths in children under five, the balance shifts. The mutated gene is present in up to 40% of the population, meaning that approximately 2% of children are born with sickle cell anaemia.

When a specific glutamic acid residue (highlighted in magenta on the far right) is mutated to a valine it causes haemoglobin molecules to aggregate, which distorts the shape of red blood cells

Under the radar

Evolving against every new infectious disease that we encounter is not possible. Humans, with our relatively slow reproductive rate, take a long time to develop new, beneficial mutations. This is why many infections, such as the common cold caused by the rhinovirus, have evolved to avoid affecting humans severely. Catching a cold will not affect the ability to reproduce, which is the main driving force behind evolution. Without this evolutionary pressure, humans do not appear to have developed mutations to specifically deal with the rhinovirus. Keeping the host able and mobile also has the benefit of boosting the spread of the disease. If the host feels well enough to leave bed and go to work, then the rhinovirus is presented with a wide range of potential hosts with every sneeze.

The immune system provides a flexible defence against a huge variety of diseases, lessening the need to evolve in response to new infections. The system learns to recognise a part of the pathogen known as the antigen, which allows the pathogen to be targeted. This means that a strain of rhinovirus, or any pathogen, that has mutated its antigen can evade detection by the immune system for longer. Unfortunately for us, this happens very often as the rhinovirus mutates very easily and reproduces incredibly quickly, allowing a huge number of mutations to accumulate within a population rapidly.

Gaining ground

Today the risk of dying from an infectious disease is lower than at any point in human history. After thousands of years locked in an impasse with diseases, we have finally developed an advantage through modern medicine. Although it seemed that we have surpassed the power of evolution, pathogens are still working towards breaking through our defences. Whether it is a new strain of flu or an antibiotic-resistant superbug, if we want to maintain our advantage it will take all the running we can do.

Note: this post was updated 16:53 GMT 21/10/2012 to remove any suggestions that Plasmodium falciparum is a bacterium