Migraine and evolution: why do the ‘migraine genes’ defy selection?

Migraine and evolution: why do the ‘migraine genes’ defy selection?

Our genes are subject to the laws of evolution. Since the beginnings of humanity, they have undergone constant change, and still do to this day. We know that the course of evolution intends for traits which only cause disadvantages for their owners to disappear from the genetic material of the species sooner or later. This is also the case for us humans.

Migraine – or rather, the predisposition to fall ill with migraine – is influenced by a range of genes in the human genetic make-up, among other things. These genes are also subject to the laws of evolution. People suffering from migraine know that this illness causes significant disadvantages for those affected. How then can we explain the fact that the genes which are partly responsible for migraine have not been removed from our genetic material over time through selection, but continue to be passed on to our descendants?

Why do the migraine genes persist?

Elizabeth Loder, a headache expert at Harvard Medical School in Boston, USA, has given this topic some consideration. Her central question is: why do genes which cause susceptibility to severe headaches continue to exist? In this context, it is particularly interesting to note that not only has migraine not disappeared over the centuries, but its prevalence is in fact increasing.

In the search for possible reasons, Loder uses explanatory models from so-called “Darwinian medicine” – an approach which was developed at the beginning of the 1990s by Randolph Nesse (American doctor and evolutionary biologist) and George Williams (American evolutionary biologist). Among other things, this branch of research examines the possible adaptive value of genetically determined vulnerability with regard to illnesses. The question is: are there situations in which genes with clear negative effects could provide an advantage through their effect on the individual’s other characteristics? When applied to migraine, this means: if it can be shown that the very genes which are responsible for a susceptibility to migraine in their carriers also come with advantages which outweigh this drawback from an evolutionary perspective, then we could explain why, to this day, these genes have not been removed from human genetic material.

A ‘cost benefit analysis’: looking after the brain effectively vs. migraine suffering

In the first explanatory approach, the so-called trigeminovascular system plays a decisive role. This meshwork of nerves and blood vessels stretches to the outer areas of the cerebrum with its processes and also innervates the meninges and their blood supply. If there is a potentially life-threatening situation, the nerve cells instantly release vasodilators, including the so-called “Calcitonin Gene-Related Peptide (CGRP)”. This substance is a potent vasodilator which causes the large cranial blood vessels to widen. This ensures an adequate blood supply. However, CGRP is also suspected of playing a causal (pathogenetic) role in the development of migraine.

The particular ability to dilate the brain’s blood vessels quickly and particularly effectively can be valuable because, in an emergency, it can prevent supply shortfalls in the brain and therefore ensure survival. Migraine would then develop as a kind of ‘side effect’ to this very effective type of regulation of the brain’s blood supply. One explanatory approach would then be: evolution accepts the development of migraine as the “price” of the organism having this kind of rescue mechanism. In a cost benefit analysis, a considerable advantage (surviving a circulation crisis) is gained in exchange for a – from an evolutionary perspective – small disadvantage (the migraine). This is why the responsible gene loci have not yet been removed from the genetic material through selection.

Sensitivity to smell as an evolutionary advantage?

Migraine patients frequently exhibit a particular sensitivity, sometimes even an outright aversion, to smells. This observation prompted scientists to speculate the following: in the early days of human development, this trait may have proven useful because it also hinders or even completely prevents poisons or other harmful substances which are ingested through the nose from entering the olfactory organ and therefore the organism. The olfactory nerve is the only sensory nerve which is directly connected to the brain, without any interposing neural connections, specifically to the so-called olfactory bulb in the telencephalon (“endbrain”). Hazardous substances which enter through the nose therefore have immediate access to our central nervous system, which potentially poses a major risk for the organism. A distinct aversion to certain odorous substances may have been very advantageous to human development because it kept the affected person’s brain from becoming damaged – undoubtedly a clear benefit in terms of the survival of the species.

A decisive factor: evolution never rushes

The central nervous system of people with migraine has several specific characteristics. It is particularly sensitive to all kinds of input from its environment, especially when the sensory area of the trigeminal system is stimulated. Affected people therefore often have a lower stimulus threshold not only for odours, but also for other sensory stimuli such as light or noise, and their pain threshold is also reduced. Additionally, the so-called chronological tolerance is lower, meaning that things like skipping meals or an irregular sleep rhythm have a particularly severe effect on affected people. General resistance to stress is also reduced.

However, the following always applies: the central nervous system of people with a predisposition to migraine is characterised by a fast processing speed for all types of signals.

Now, our modern living environment seems to present a particular challenge for people with these predispositions: overstimulation, the hectic pace of everyday life, sleeping problems, and irregular eating are classic migraine triggers, and we are confronted with them far more frequently today than was ever the case during the vast majority of our ancestral development so far. This is consistent with the observation that the prevalence of migraine is generally increasing. It is possible that the effects of the predisposition to migraine that has already existed in humans for a very long time are simply greater today because the triggers are more widespread. Perhaps we have always had migraine in our genes, but have only realised in the last few centuries that it can manifest in such painful ways. The mechanisms of evolution could not yet have any effect on this newly developed form of suffering because evolution is – from our perspective – a lengthy process. We must remember: the last few centuries of human history are merely the blink of an eye compared to the temporal dimensions in which the evolution of our species takes place.

In conclusion: the evolutionary bill (still) adds up

As an illness, migraine could be the result of a ‘deal’ made by evolution. Potentially, but not permanently or severely, harmful genes such as the migraine gene could therefore continue to exist and remain in the genome because they come with several advantages which are great enough to be of overriding benefit. Ensuring blood flow to the brain or protection from toxins, for example, can keep the individual safe from dangers which could, in the worst case, lead to their death. The ‘side effect’, the migraine, then seems less significant by comparison. From an evolutionary perspective, suffering from migraine is therefore a reasonable ‘price’ in light of these advantages. With everything that we currently know, it can be said that the genetic predisposition to migraine exists to this day because it continues to be acceptable in the evolutionary ‘cost benefit analysis’. It comes with selective advantages which were beneficial for other important aspects of human development, and potentially still are to this day.