Evolution and disease

Evolution and disease

By Niladri Banerjee


Human evolution is a subject of intrigue and fascination for many. How did we originate? Where did we come from? Where are we headed? While the latter question is philosophical in nature and cannot be fully answered by science, we do know some of the answers to the earlier questions.


It is a generally accepted notion in science, thanks to the pioneering work of Charles Darwin in his book The Origin of Species, that all existing life has been derived from pre-existing life. It is a seminal book written in 1859 and is considered the foundation of evolutionary biology. Thus humans or Homo sapiens, in scientific jargon, came into existence due to successive adaptations to environmental pressures across millions of years. Such kind of pressures can cause favourable selection of specific traits or characteristics that provide a survival advantage to the individual. In other words, individuals possessing such a trait will likely survive and thus pass on the trait to their children. If the environmental pressures remain in place for several millennia, only individuals possessing those traits will remain. It is generally understood that present-day tree dwelling apes and humans shared a common ancestor several million years ago. A classic example highlighting the adaptations and subsequent evolution of humans in response to environmental pressures is the nuchal ligament that runs behind the neck. It is present in humans but absent in other great apes. It works to stabilize the neck while running and prevents it from bobbing up and down. It was positively and permanently selected in the human population about 2 million years ago.


However, an intriguing aspect of evolution that has not been explained satisfactorily by Darwin’s work is the emergence of diseases; genetic and neuropsychiatric diseases especially. Why should there be genetic diseases at all? Diseases are negative traits and reduce the likelihood of offspring. So shouldn’t evolution have removed them? While common sense suggests so, this is not always the case. For example, the disease ‘sickle cell anaemia’ is a disease ‘favourably’ selected by evolution – it provides resistance to malaria at the expense of the oxygen carrying capacity of our red blood cells. Basically, in this disease, the disc shaped red blood cells become misshapen and crooked. This reduces the ability to carry oxygen. However, the malaria pathogen is unable to attach to such misshapen blood cells. Thus in areas where malaria is endemic, people with misshapen blood cells will survive.


This aspect of evolution has begun to attract the attention of researchers worldwide. Thanks to the growth and development of advanced genomics technologies, it is now possible to tease out some of the reasons for the emergence of diseases from an evolutionary point of view. To those who are unfamiliar with the term ‘genomics’, it refers to the study of the ‘genome’ of an organism. The ‘genome’ is the net sum of information coded in the DNA of the organism, in other words, studying the complete DNA sequence of an organism can be termed ‘genomics’.


One may ask how can we answer evolutionary questions via genomics? After all, the traditional method of understanding human evolution  was anthropology, which involved amongst others, excavation of ancient human fossilized bones, ancient settlements etc. to piece together the trajectory of human evolution. The answer lies in the fact that our genome holds ‘snapshots’ of evolution preserved for all eternity in all members of a species. Since nature weeds away that which is not needed, it is possible to compare genomes of progressively older organisms, such that we can see those specific portions of the genome that have not changed (and are thus important) across all the organisms surveyed. In this way, we can figure out those genomic regions which are essential for life itself and also, for a particular group of organisms (e.g. mammals v/s reptiles) as well as individual species in an organism group (e.g. dogs v/s cats v/s chimpanzees v/s humans)


One particular disease this method is being employed to study is schizophrenia.   It is a severe mental disorder characterized by auditory hallucinations, reality distortions, apathy and extreme paranoia with social withdrawal, amongst others.  In the public domain, movies like ‘A Beautiful Mind’ and ‘Fight club’ provide some ‘glamourized’ depictions of the disease. It is one of the oldest known diseases to man, with descriptions of the disease dating back to Ancient Greek times. How and why this disease originated is unknown. It is also not known why the disease persists in the human population at a rate of 1 in every 100 individuals. After all, a person afflicted with this disorder is less likely to reproduce. Yet, the disease persists.


About 20 years ago, some researchers postulated that schizophrenia may be the price for becoming human. In other words, the very act of transforming into Homo sapiens may have led to the emergence of the disease. At the time this idea came into being, it was nothing more than a theory to some and speculation to others. However, rapid progress has been made since the turn of the millennium.  Researchers have begun to unravel tell-tale genomic signatures which point to a fact : genetic variants leading to susceptibility to schizophrenia seem to have piggy-backed on genetic variants leading to superior/creative intellectual abilities and/or genomic regions ‘selected’ for evolving into humans.  Research for example has shown higher than normal occurrence of schizophrenia amongst creative and artistic peoples.


Our group has now begun to look at an additional aspect of these genomic signatures. We are looking into the ‘epigenetics  ‘of disease origins. Epigenetics can be understood as the bridge connecting environmental influences to genes. While mostly temporary, some epigenetic effects (chemical modifications on the DNA sequence) are long lasting and can be inherited . One may wonder what extra information could we gleam with evolutionary epigenetics? For starters, we can pinpoint the precise regions of the genome that likely changed due to environmental influences. With this knowledge, it can be possible to determine a) Why these specific regions were influenced, b) Why these regions were important for the evolution of our species, and c) What kind of environmental influences would have been required to produce such changes. With our research, we hope to elucidate the role epigenetics may have played in the growth and emergence of various complex disorders.