Editorial 1 : ‘Zombies’ in our genes helped us evolve, and could help fight cancers
Introduction
Viruses are ubiquitous entities that have long plagued humans, often presenting in pesky, self-limiting infections, like a bout of the common cold. However, this battle between host and pathogen churns up a fascinating question: could viral infections have reshaped the human genome in the process?
A unique enzyme
- Most viruses can’t really affect the genome. However, retroviruses buck this trend: they are a group of viruses that can integrate and reshape the genomes of the hosts they infect.
- Retroviruses have an RNA genome; can reverse-transcribe it to DNA and thus insert it into the host’s genome.
- Their name comes from a unique enzyme they possess, called reverse transcriptase.
- It’s the one with the ability to convert the virus’s RNA into a corresponding DNA sequence.
- The knowledge that these viruses could cause cancer was even then well-known, even if the mechanism wasn’t clear until the 1971 teams’ reports.
The discovery of HIV
- But it wasn’t until 1980 that researchers — Robert C. Gallo & co. — found the first human retrovirus.
- Dr. Gallo had extensively worked on the human T lymphotropic virus (HTLV) and his group isolated it from a patient with cutaneous T-cell lymphoma.
- French researchers initially called the virus the lymphadenopathy-associated virus (LAV) while American researchers called it HTLV-3.
- Both these names were superseded by the name ‘human immunodeficiency virus’ (HIV) in 1986.
- For their discovery, Dr. Barré-Sinoussi and Dr. Montagnier were awarded the medicine Nobel Prize in 2008.
Genomic elements left behind
- In the life cycle of a retrovirus, the reverse-transcribed DNA is integrated into the host’s DNA along with another enzyme called integrase, which acts like glue to bind the two DNA genomes.
- Once bound, the viral DNA is called a provirus, and is complete with all the ingredients it needs to be functional.
- At the end of this process, the virus practically hijacks human cells and turns them into virus-making factories.
- It’s typically not possible for a person to inherit retrovirus infections or even the provirus because these integrations usually damage only a subset of cells.
- However, such genome invasions can sometimes mess up the integration process, causing ‘zombie’ regions in the host’s genome.
- These parts are called endogenous retroviruses (ERVs).
- ERVs usually can’t replicate and produce functional proteins since they lack their regulatory regions.
- If the abortive integrations involve the germ cells — i.e. those that produce the gametes, sperm cells and ova — the host will be able to transmit its ERVs to its offspring. This happens in rare instances.
- This said, over the tens of thousands of years of mammalian evolution, many retroviruses have left a number of genomic elements in the genome, sort of the genetic fossils of early infections.
- These elements have long lost the potential to produce viruses but researchers believe they have played a big hand in the evolution of their hosts.
- In fact, research strongly suggests around 8% of the human genome is composed of ERVs.
Biomarker for preeclampsia?
- A good example of their influence are the syncytins, a class of genes thought to be descended from an ERV.
- That is, these genes originally came from viruses and were acquired by chance as the mammalian host evolved.
- But at some point they became essential for the host because they helped create the placenta, an organ that became crucial to support a growing baby.
- This change is thought to have been important for the evolution of mammals with placentas from their egg-laying ancestors.
- Over time, the original ERV’s envelope gene (env) was thought to be modified or replaced by new versions, forming the syncytin genes as we see today in different mammal species.
- Syncytins are important genes involved in placental development; many ERVs are also highly expressed in the placenta.
- In a recent paper in China reported that a particular RNA was dysregulated in early-onset preeclampsia — a condition during pregnancy where the blood pressure shoots up.
- This RNA was derived from an ERV. The study also suggested that the presence of this RNA could be used as a biomarker for the condition.
Tumours in colorectal cancer
- ERVs are also involved in cell-type differentiation. In the early stages of embryo development, cells transition from totipotency (the ability to become any cell type) to pluripotency (the ability to become the three primary germ cell types).
- This transition is important because it produces pluripotent stem cells that can form different cell types.
- Scientists recently discovered a protein called MERVL-gag derived from an ERV.
- They found MERVL-gag plays a key role in controlling some other proteins during this transition.
- They also found MERVL-gag works closely with another protein called URI, which helps the embryo transition from totipotency to pluripotency.
Way forward
In future, as research techniques continue to advance, scientists may uncover more wonderful insights into the evolutionary significance of ERVs and their contribution to human biology. Such knowledge will undoubtedly lead to breakthroughs in regenerative medicine, cancer therapies, and personalised medicine, ultimately enhancing our understanding of human health and evolution.
Editorial 2 : On discarding indexation for LTCG
Context
Finance Minister Nirmala Sitharaman’s proposal that long-term gains on all financial and non-financial assets would now be taxed at 12.5% instead of a tiered structure, albeit abandoning indexation.
What purpose does indexation serve?
- Imagine, an individual buys a house for ₹10 lakh in 2001. For reasons such as inflation and/or a vibrant property market, they are able to sell the same property in 2021 at ₹75 lakh. Here, it may appear that they gained ₹65 lakh and should be taxed accordingly.
- However, the figure does not consider the price levels prevailing at the time of sale with that of purchase. This is where the Cost Inflation Index (CII) comes in.
- Indexation ensures that taxpayers are taxed on real gains than gains at prevailing prices, which are a result of general increase in prices, and not economic growth, during the course.
- In the stated example, the CII for 2021 (that is, 317) would be divided by that for the base year 2001 (100) to derive a number.
- It would then be multiplied with the purchase price (that is, ₹10 lakh). Thus, the indexed cost becomes ₹31.7 lakhs and the individual’s taxable gain is revised downwards to ₹43.3 lakhs.
- At the erstwhile 20% rate, they would now be required to pay a long-term capital gains tax of approximately ₹8.7 lakhs.
- With the new system however, the ₹65 lakh would be taxed at a lower 12.5%. Thus, a tax liability of ₹8.13 lakh.
What is the issue?
- Economists say that the eventual tax liability is broadly determined by two factors, that is, the rate on return and the subjected time-period.
- In this light, it is essential to note that not all assets may experience the same exponential growth as in the example above. This could be because of a flat market or a temporary period of slump.
- This is primarily where the indexation turns out to be more favourable.
- To illustrate, let us say that in 2021 instead of ₹75 lakh, the house is sold for ₹40 lakh. When adjusted with indexation, the tax liability is ₹1.66 lakh against ₹3.75 lakh without indexation.
- Furthermore, a study, basing an assessment from the RBI’s House Price Index, observed that without indexation, LTCG tax went up about three times on properties purchased after 2010.
- From zero tax liability across the board, we see significant liabilities arising for these years (since 2016-17), the study found.
- The Income Tax department, however, estimates that real estate returns (12-16% per annum) are much higher than indexation for inflation (4-5%), depending on the period of holding.
- Therefore, it predicts “substantial tax savings” to a “vast majority” of taxpayers.
- According to economists, an individual stands to benefit more from the revised provisions if they sell the assets expeditiously (say, 3-4 years) instead of holding it for a longer-time period (say, 10 years or more).
- Furthermore, he explained that with the change, real-estate investment trusts (REITs) and infrastructure funds stand to suffer because they do not have the same high rate of returns as an equity market.
What does this mean for assets?
- Removal of indexation is adding dampness to the overall sentiment, the reduction of the base rate of tax was providing balance to the dampness.
- A lot depends on the nature of the asset, the time when the asset was purchased .
- Based on this, it would continue to lead to different reactions from various sections of the society.
- For real estate, those looking to buy a second house for the purpose of investment may potentially refrain from doing so. They would have to sell if off quickly to profit from the revised provisions
- The paradigm however is potentially minimised, according to him, for those who intend to buy a house to reside themselves.
- Pertinent to note here, the Income Tax department clarified that for assets acquired before April 1, 2001, the individual would have the option to choose between fair market value as on that date (April 1, 2001) and the actual cost of acquiring the asset as the basis to compute the capital gain on sale.
- This paves the way for an indexation cushion for pre-2001 acquisitions.
Conclusion
- The other set of concerns entail potential sale of properties at circle rates (minimum price at which a real estate is to be sold) only.
- Undervaluing the real estate helps furbish lower capital gains, thus, lesser taxation.
- Further, Mr Chadha also warned about increased black money transactions in the sector — another means to hide gains.
