Editorial 1 : X chromosome revival in older women increases risk of autoimmune disease
Introduction
In mammals, the females have two copies of the X chromosome, while the males carry a single copy. The X chromosome is more significant for its role in determining sex. Recent genomic studies suggests that it plays a part in a variety of biological functions as well as controlling the sex-specific susceptibility to certain diseases.
The X chromosome
- The human X chromosome encodes around 800 genes, which in turn code for proteins. A loss of function for these genes could thus lead to a variety of genetic diseases.
- Broadly, the diseases whose onset and/or progression the X chromosome influences can be grouped into three types: (i) X-linked genetic diseases, (ii) diseases influenced by XCI escape, and (iii) those linked to X-chromosome aneuploidy.
- There are more than 500 X-linked genetic diseases, and they mostly affect males.
- Many of the X-linked traits and diseases are not uncommon in the general population. For example, red-green colour blindness is X-linked, and affects around 8% of males.
- Duchenne muscular dystrophy, caused by mutations in the dystrophin gene and affecting 1 in every 3,500–5,000 boys born in India and agammaglobulinemia, an immunodeficiency disorder that affects around 1 in 200,000 live births, are also X-linked.
- Scientists are also aware of numerical abnormalities — or aneuploidies — of the X chromosome. For example, Klinefelter syndrome is characterised by an extra X chromosome (XXY) and Turner’s syndrome by a loss of one X chromosome in females (X instead of XX).
Inactivation of X chromosome
- In 1961, an English geneticist argued that since females have two copies of the X chromosome, one of the X chromosomes is randomly inactivated during early embryonic development, in a process called X chromosome inactivation (XCI), to prevent the overexpression of X-linked genes in females.
- In this process, epigenetic changes silence most genes on one X chromosome (epigenetics refers to the processes by which genes are influenced by the environment in which they operate).
- XCI ensures a balance in gene expression, but scientists are also learning that it plays a role in various genetic disorders.
- Issues such as incomplete inactivation (a.k.a. escape) or skewed inactivation can lead to the abnormal expression of genes, which contributes to diseases including X-linked disorders, certain cancers, and autoimmune conditions.
- Three decades after Dr. Lyon’s hypothesis, researchers unravelled the molecular mechanisms of X inactivation when they discovered Xist, a non-protein-coding RNA.
- The body deactivates the X chromosome with the help of Xist and another non-protein-coding RNA, called Tsix (reverse of Xist).
- The differential regulation of these two genes means that in the X chromosome that is to be deactivated, the Xist RNA is overexpressed such that it coats or covers the chromosome.
- However, inactivation of the X chromosome is not absolute. As many as a fourth of all genes encoded by the X chromosome could escape inactivation and express themselves.
Autoimmune diseases
- Researchers have suggested for a while that a number of immune diseases — including systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome — are more common in females than males. Of particular note are autoimmune diseases, in which antibodies act against specific proteins
- Researchers perturbed the expression of Xist — which triggers XCI — in female mice, and found that previously inactive genes on the inactive X chromosome were reactivated.
- This was particularly true of genes involved in the Toll-like receptor 7 signalling pathway in immune cells.
- The result was the spontaneous development of lupus-like inflammatory signs in the female mice, including an increased level of autoantibodies and altered immune cell populations.
- The resulting effects in autoimmune diseases are likely due to a combination of reactivation events in different cell types and global changes in gene expression. The findings reinforce the molecular link between altered XCI and autoimmune diseases, and pave the way for possible new drugs to treat them in the future.
X and Alzheimer’s disease
- Another disease with a sex bias and linked to the X chromosome is Alzheimer’s disease. Women seem to have a higher risk of getting it; worldwide, almost twice as many women have Alzheimer’s as men.
- In a study it was found that a gene called ubiquitin-specific peptidase 11 (USP11), involved in a protein-modifying process, encourages tau protein to accumulate in the brain.
- Based on studies of mice brains, the researchers suggested the gene escapes X inactivation and is expressed more in females.
Way forward
In humans, the Y chromosome has been shrinking over time, so the X chromosome is possibly evolution’s best bet and thus plays a pivotal role in human health and disease. Its evolutionary genomics and emerging insights into its participation in biological processes illuminate the complex interplay between genetic inheritance, epigenetic modifications, and disease manifestation. Cracking all this to get the full picture could also lead us to new drugs and therapies.
Editorial 2 : Analysing local environmental footprints
Context
While climate change is a global concern, issues such as water scarcity and air pollution are often localised or regionalised. Focusing on local environmental issues is crucial; and herein comes the importance of understanding household environmental footprints.
Distribution of household environmental footprints in India
- A recent study highlights the environmental impact of affluent individuals, particularly those who engage in consumption beyond basic needs.
- This study specifically examines the CO2, water, and particulate matter (PM2.5) footprints associated with luxury consumption choices among households in India across different economic classes.
- The analysis contrasts these luxury consumption footprints with those associated with non-luxury consumption. The luxury consumption basket includes various categories such as dining out, vacations, furniture, social events etc.
Key findings
- The study reveals that all three environmental footprints increase as households move from poorer to richer economic classes.
- Specifically, the footprints of the richest 10% of households are approximately double the overall average across the population.
- A notable surge in footprints is observed from the ninth to the 10th decile, with the air pollution footprint experiencing the highest increase at 68% in the 10th decile compared to the ninth.
- Conversely, the rise in the water footprint is the lowest at 39%, while CO2 emissions stand at 55%.
- This suggests that Indian consumers, particularly those in the top decile, are still in the ‘take-off’ stage, with only the wealthiest segment exhibiting substantial increases in consumption-related environmental footprints.
- The heightened footprints in the 10th decile are primarily attributed to increased expenditure on luxury consumption items.
The key contributors
- The study identifies eating out/restaurants as a significant contributor to the rise in environmental footprints, particularly in the top decile households, across all three footprints.
- Additionally, the consumption of fruits and nuts is highlighted as a factor driving the increase in water footprint in the 10th decile.
- Luxury consumption items such as personal goods, jewellery, and eating out contribute to the rise in CO2 and air pollution footprints.
- While transitioning from biomass to LPG reduces direct footprints, the lifestyle choices associated with affluence lead to a rise in PM2.5 footprints (and subsequently, the CO2 footprint).
- The average per capita CO2 footprint of the top decile in India, at 6.7 tonnes per capita per year, is noted to be higher than the global average of 4.7 tonnes in 2010 and the annual average of 1.9 tonnes CO2eq/cap required to achieve the Paris agreement target of 1.5°C.
- While still below the levels of the average citizen in the U.S. or U.K., this disparity underscores the need for urgent attention from policymakers.
- Given the influence of elite lifestyles on broader societal aspirations, policymakers should prioritise efforts to nudge consumption levels of affluent households downwards to align with sustainability goals.
Conclusion
- The study emphasises that while sustainability efforts often focus on global climate change, global environmental footprints do not necessarily align with local and regional scale footprints.
- However, local and regional environmental issues exacerbated by luxury consumption disproportionately affect marginalised communities.
- For instance, water scarcity and air pollution disproportionately impact marginalised groups, further marginalising them, while affluent sections can afford protective measures such as air-conditioned cars and air purifiers.
- This underscores the importance of multi-footprint analysis in addressing environmental justice concerns and ensuring equitable sustainability efforts.