A Darwinian Trade Off: New Study Shows That Some Genes Responsible For Cognitive Ability And Immunity Also Cause Mental Diseases Later In Life

Have you ever noticed that when people get older their personalities change? That often mental diseases start surfacing during the old age? Why is it so?

There may be an evolutionary answer to these quirks of human life.

Scientists from two distinct disciplines, namely, cognitive science and genomics, have uncovered an interesting connection. Clinicians at NIMHANS, Bengaluru and geneticists from the Institute of Genomics at University of Tartu, Estonia, have conducted a study that points to an evolutionary basis to the manifestation of what are called severe mental illness (SMI), such as schizophrenia, bipolar disorder, dementia, obsessive compulsive disorder and addiction.

One important aspect that the scientists noted is that the uniform prevalence of the diseases across populations shows that there seemed to have been ‘little impact on selection for fitness.’ But what actually could have happened, as the research suggests, is that earlier selection could have created ‘a bias towards certain kinds of variation, that may cause disease later in life.’ So, the same processes which ‘may protect against inflammation or infection when young, only to predispose towards disease when one is older.’

The study compared the genetic sequences of exomes (the gene sequence regions that are translated into proteins) from individuals of 80 unique individuals from India coming from families with two or more individuals with severe mental illness and compared them against the African and the South Asian population.

Through a method called Population Branch Statistics (PBS) they identified 74 genes as candidates for positive selection. Positive selection or Darwinian selection is that process where a manifestation of a particular gene sequence gets selected because of the advantage it confers and starts to dominate in the gene pool of a species.

The genes thus identified for positive selection are those involved in ‘immunological and defense responses, including activation and regulation of interferon-gamma, cytokine and immune system, and different signaling pathways’ explains Dr. Ajai K. Pathak, the lead author of the study who is with the Institute of Genomics at University of Tartu.

Of these 74 genes identified for positive selection, almost 20 genes – that is 1/4^th – have been found to be implicated in in the risks of schizophrenia, dementia, Parkinson’s disease etc and also general attributes such as intelligence and cognitive abilities. Dr.Pathak explained to Swarajya, ‘It is seen that genetic variants that cause mental illness or schizophrenia, many times are significant to cognitive ability and immunity of individuals.. And probably that's why these variants go through positively selection as they provide fitness in other cases.’

That is a very interesting Darwinian trade-off he points out, ‘Cognitive ability and immunity are more important and useful for survival than the diseases they bring along with.’

Another senior author of the paper, Dr. Mayukh Mondal said, ‘We also looked for evidence of Neanderthal genes in the sample, as the persistence of these ancient genomes in modern humans seems to correspond to some traits, as well as risk of disease.’

Dr. Pathak pointed out that while a few papers have already brought out the presence of Neanderthal elements in the South Asian population, in this study the team discovered Neanderthal derived genome in one of the genes - AHNAK2 gene. But while usually Neanderthal-derived elements have significance for adaptive value, this particular Neanderthal SNP has no such value in the context of the problem studied.

Dr. Meera Purushottam of NIMHANS, one of the authors, pointed out to the complex relations between neuro-immunological dynamics and the gene expression in the press release related to the paper:

Dr. Jayant Mahadevan, also of the Department of Psychiatry of NIMHANS, a lead author of the paper pointed out how the study ‘adds to the growing evidence that the risk of psychiatric disease may be linked to variations in the shared gene pool, which in turn depends on the evolutionary history of the species.’

With rapid increase in human population as well as increase in human longevity, the selection forces acting on our genomes are changing fast. The long evolutionary history has accumulated changes and that genomic reservoir is now getting challenged and churned by these new developments we have imposed on ourselves. What is a good trade-off that has successfully helped our species develop immunity and cognitive abilities, may now also be found to be involved in the old age life-cycle related miseries.

Studies like the above which explore the complex interconnections between the evolutionary history of our genome and its relations to our neuro-dynamics help a great deal in that direction.

So, can there be an epigenetic dimension to this?

Dr. Pathak pauses. This is right now purely in the realm of speculation. Nevertheless, he answers:

The research was conducted as part of a project funded by the Dept. of Biotechnology, Govt of India, and the Pratiksha Trust: Accelerator program for Discovery in the Brain using Stem cells [ADBS]; and is a collaboration between NIMHANS, NCBS (TIFR) and InStem. The ADBS program is an umbrella effort, that integrates many aspects of in-depth study of mental illness; from clinical assessments, to imaging and physiology, to genetics, genomics and stem cell biology. Dr Jayant Mahadevan and Dr Ajai K. Pathak are the lead authors; while Dr Meera Purushottam and Dr Mayukh Mondal led the scientific analysis. Dr Pathak and Dr Mondal are at the Estonian Biocentre, Institute of Genomics, Tartu, Estonia; and the other collaborating clinicians and scientists are from NIMHANS, NCBS and InStem.

-Journal Reference.