Editorial 1: Somatic mutations: a genomic revolution hiding inside our cells
Context
- Scientists have known of somatic variants and their role in diseases for many years now, but there has been an explosion in the amount of data and knowledge only recently due to our ability to sequence the genetic material in individual cells
Human chromosomes
- The human genome has 23 pairs of chromosomes, one inherited from each of our parents.
- The genome is the blueprint of our genetic makeup. The ovum and the sperm carry these blueprints from our parents.
- After fertilisation, the combined single cell, with the 23 chromosomes, starts to divide, copying the genetic material over and over to nearly a trillion cells – which make up the human body.
- As the cells divide, the DNA is copied with extremely high accuracy thanks to proteins that proofread and correct errors in the DNA.
- But despite this mechanism, various studies have estimated that there is still an error rate of 0.64-0.78 mutations per billion base pairs per division. But this rate is also minuscule given the large size of the human genome.
‘Copy-paste’ mistakes
- An error that occurs in the DNA after birth but during development is called a somatic genetic mutation.
- Their occurrence is driven by the repeated ‘copy-pasting’ of the genome – which means there will be more somatic genetic mutations the older an individual is and the higher the turnover of the tissue.
- Turnover is the replacement of old cells with new ones.
- Sometimes, a somatic genetic mutation can render a cell fitter than others, which leads to the formation of tumours. So these mutations are called driver mutations.
- In their genomic composition, these cells are similar to each other, but still different enough thanks to a handful of genetic variants.
Knowledge explosion
- Somatic genetic variants are important for a number of normal physiological processes.
- For example, the immune cells in our body, which produce antibodies, undergo an enormous amount of somatic changes to create diverse proteins. These proteins recognise and bind to specific pathogens, forming a ‘library’ of cells, each with a specific protein.
- During an infection, the body selects cells from this library, depending on which can bind to a pathogen better, and uses them to make antibodies.
- Specifically, using advanced microfluidics and high-throughput sequencers, we can now sequence tens of thousands of cells from a tissue at the same time, opening big windows into genes and the functional diversity of cells in the human body.
Cancer’s signatures
- Somatic genetic variants play an important role in the development of cancers.
- We now know that somatic changes can cause a cancer to develop and that cancers can accelerate the development of somatic changes. So they can help with early detection, diagnosis, and prognosis.
- Early detection and diagnosis of cancers rely on the fact that certain patterns – called mutational signatures – of genetic variations are characteristic of specific cancers.
- There are technologies to detect DNA from tumour cells that has ‘escaped’ the cells into blood or fluids, to spot a cancer early.
Under-recognised cause
- The other major application for somatic changes is in the development of genetic diseases.
- Many genetic conditions arise from somatic genetic variants. Obviously, these conditions are not inherited from either parent but are due to new genetic variations that have arisen during development.
- In some instances, somatic changes can be beneficial in a genetic disease – by changing a deleterious change to a normal one, a phenomenon known as revertant mosaicism.
- For example, around 10% of cases of Wiskott-Aldrich syndrome, a rare genetic immunodeficiency, have been found to have revertant mosaicism, as a result alleviating the severity of the disease in many individuals.
SMaHT Network
- The U.S. National Institutes of Health recently launched a programme focused on understanding the breadth of somatic mosaicism Called the ‘Somatic Mosaicism across Human Tissues’ (SMaHT) Network.
- it aims to catalyse our study of the field by discovering somatic variants, developing tools and resources with which to study them, and improving our ability to analyse, interpret, and organise them in different biological and clinical contexts.
Conclusion
- As we plumb more intricate depths of the cells that we are made of, and their wondrous diversity, we also take strides on the road to usher in innovative approaches to understand and manage the diseases that assail us. The ability to scrutinise our genes at the level of single cells also empowers us to reshape our understanding of the fundamental aspects of evolution.
Editorial 2: Himalayan blunders that are ravaging the Himalayas
Introduction
- Wonder-struck by the beauty and the magnificence of the Himalaya, the snow-covered peaks, though increasingly diminishing, may still awaken the poet in us, but the barrenness of the hills below tell us the real story — that of steady environmental depredation.
About
- Today, the repeated tragedies of bridges, roads and buildings being swept by raging rivers in the hill States of Uttarakhand and Himachal Pradesh, epitomise a flawed developmental paradigm institutionalised in an eco-fragile region.
- Blocked roads after a landslide at Chamoli and sinking in Joshimath in Uttarakhand, road caving in Chamba in Himachal, accidents on the Char Dham routes, and deaths on the all-weather road are reports that have become everyday news from “Devbhoomi” (land of the gods).
Road project, bypassing the rules
- In 2016, the Chardham Mahamarg Vikas Pariyojna, a massive infrastructure project of road widening to double-laning with a paved shoulder (DLPS) design was implemented in the Garhwal region and a short stretch of Kumaon in Uttarakhand.
- The project has claimed lakhs of trees and acres of forest land, many human and animal lives, and also the fertile topsoil of the fragile Himalaya.
- By law, a project of more than 100 km needs environmental clearance. But ambitious projects for tourism and plans that are the result of election agendas are time bound.
- All laws of land are bypassed. In this case, this massive project was broken up into 53 small projects, each less than 100 km long, thus by-passing environmental impact assessment (EIA) requirements.
- The dense forests around Chamba, Agrakhal Maletha, Shivpuri, Rudraprayag, Chamoli, Agustmuni, Karnaprayag and Kund (all Uttarakhand) and other such lush green sites are vanishing.
- Amid the rapacious nature of the Chardham Mahamarg Vikas Pariyojna, only one pristine patch, i.e., the Bhagirathi Eco Sensitive Zone (BESZ), remains.
- BESZ has the only natural free flow that is left of the Ganga river and was declared a protected site in December 2012 under the Environment Protection Act, 1986.
The underlying issue
- BESZ stretch is of approximately 100 km could not be touched by the Chardham Mahamarg Vikas Pariyojna project without an approved zonal master plan (ZMP) and a detailed EIA.
- To facilitate the Chardham Mahamarg Vikas Pariyojna, the ZMP was given hasty approval, negating the directions of even the Supreme Court of India.
- The mandatory and detailed EIA was not done. And, finally, the BESZ monitoring committee’s approval was overseen by most of the State officials on the committee without any discussion or suggestions being made.
- While experts have repeatedly pointed out that the Chardham shrines of Uttarakhand are already overburdened, their carrying capacities have been increased ignoring all scientific rationale to blindly boost the tourism sector and perhaps to justify the excessively road widening that the government is pursuing in the most vulnerable section of Himalaya.
- However, after the recent warning signals by mother nature, the State governments of Uttarakhand and Himachal Pradesh propose a reassessment of carrying capacity.
- The Supreme Court too is setting a committee for the same, but the larger question is whether the recommendations will be implemented or not.
Saving the Gangotri, need for regulation
- One of the most challenging issues for the Ganga’s rejuvenation is conservation of the Gangotri glacier, which is also the fastest receding glacier.
- With an increase in vehicular movement and episodes of forest fires, black carbon deposits (carbon plus soot) are rising on the glacier, escalating its melting.
- Black carbon absorbs more light and emits infra-red radiation that increases the temperature. Therefore, an increase in black carbon in the high Himalaya contributes to the faster melting of glaciers.
- In the persistent debate of environment versus development of the hills, there is a very simple solution to all the chronic and acute problems that the hills face — regulation.
- In BESZ, the upgradation of roads to an intermediate road width, that will have minimal environmental impact, is the only possible and sustainable solution.
Way forward
- If reducing a few metres of road width helps ensure the conservation of the only pristine stretch of the Ganga and protection of the Himalaya, then we must make sincere efforts to amend the plan.
- Most importantly, no development can be sustained if it ends up destroying the main lifeline for millions of people and future generations.
