Comparative Similarities Between Indo-European Languages Reflect Ultraconservation

As I was watching the James Bond film Specter a couple of months ago, I spotted the Spanish for "The Day of The Dead", "Dia de Muertos" flash across the screen. The scene was when Daniel Craig was visiting Mexico City on an unofficial purpose. 

I was overawed once more! How could there be so much semblance between languages, given that they are spoken by people separated some several thousands miles apart? Here in this case for example, dia stands for day in English and din in Bengali; while muertos (dead) is phonetically and alphabetically related to mrityu (death, in Bangla). Not only do they retain their meanings across languages/dialects/cultures so disparate geographically but also the phonetic pronunciation remain almost intact. I have been, for a long time, amazed at the astounding similarities between English and other European languages with that of Bengali and Hindi. Please note that these similarities existed way before the British came to India: some 15,000 years ago! (see references below). More recently, "in the 16th century, European visitors to the Indian subcontinent began to notice similarities among Indo-Aryan, Iranian, and European languages." Here are only a few examples. More examples can be found here, here and here.

Phonetic Bengali [(IPA) symbols NOT adhered to]	English/other European terms with same meaning	Hindi or other ANI   Ancestral North Indians (ANI)
POOROপুরো	PURE, Full, 100%	POOREY, पूरे दशम
MRITYU মৃত্যু	MUERTOS (SPANISH)	MURDA/MURDER मुर्दा
PATH পথ	PATH	पथ
ADOR আদর	ADORE
OLI (=LANE)-GOLI অলি	ALLEY
AAGRAASON আগ্রাসন	AGGRESSION
NAAM নাম	NAME, NOM	नाम
BAWD বদ	BAD	बद
DWOR দোর	DOOR	दौर
KUTTA কুত্তা	KUTYA (HUNGARY), Dog	KUTTA कुत्ता
BHRAATAA ভ্রাতা	BRAT (RUSSIA, POLAND, UKRAINE, CROATIA), Brother	भ्राता
BAARF বরফ	[BRITISH SLANG FOR SICK]	SNOW IN FARSI, URDU, HINDI बर्फ
BOWMI বমি	VOMIT
NAWBOW নব	NEW, NUEVO	नया
	BETTER	BEHTER बेहतर
BYABOHAAR ব্যবহার	BEHAVIOUR	ब्याबोहर
আহ্নিক	DI-URNAL
সায়া কায়া ট্রিক	PSYCHIATRIC [SAYA-KAYA (BODY-MIND)]	साया _काया
ONDOR অন্দর	INDOOR	अंदर
BAAG বাগ	BURG/BURGH/Borough [E.G. KAROLBAAG, HAMBURG]	BAAG बाघ
GEET/ GITA গীত, গীতা	GUITAR [Song, E.G. BHAGWAT GITA]
OSTHI অস্থি	OSTEO (BONE)	अस्थि
SHAWTOW শত	CENTUM (HUNDRED)	शत
PAWD পদ	PEDIS	पद
BAKYO বাক্য	VOX, Voice, Word	BAKSH बाक्या
DOSHOM দশম	DECEM, TEN	दशम
বার্চ	BIRCH	BHURJYA भुर्ज्य (SANSKRIT)
AAMI আমি	ME, MYSELF	मुझे
DIN দিন	DAY, DIEM	दिन
NAASAAA, নাসা, নাসিকা	NASION, NOSE	नासा, नासिका
DEVAH দেব	DIO (GOD)	देवा
SARPA, SERPE সর্প	SERPENT	सर्प
ASTAA অষ্ট	EIGHT, OCTO (LATIN)	अष्ट
NAVA নবম	NINE, NOVE (ITALIAN)	न
SAAT সাত	SEPTEM, SEVEN, SETTE	सात
DWO দু	TWO	दो
SARKARA শর্করা	SUGAR/CANDY	SUKKAR (ARABIC) शक्कर
আদমি	ADAM	ADMI (PERSON) HINDI) आदमी
DANT দাঁত	DENTAL, TOOTH	दांत
BANDHAN বন্ধন	BONDAGE	बंधन

Well, then how are these languages so intricately related? How likely is it that the "cognates" are just coincidences? 

[Cognates are words which have the same linguistic lineage. When you do a voice search on Google Assistant or Apple's Siri, the server breaks-up your voice command into 'phonemes' and they then try to match the word that appears most likely to be spoken by comparing with its database. Cognates are thus likely to be confused by the computer since they are so phonetically similar. Generally, most cognates have a linguistic half-life of about 2000-4000 years. This means that there is 50% chance that a cognate will be replaced by a non-cognate (not similar sounding) one. But it has been seen that pronouns, numerals and some other words tend to persist much longer, and are less prone to erosion.] 

The semblance unequivocally points to a common origin; and that these words did not originate 'separately' on the planet!

However, the linguistic similarities are noticed between European and North Indian languages only. 

It has been proved by genetic analysis that most of the ethno-linguistic groups in India (and South Asia in general) originated from two separate ancestral populations: Ancestral North Indians (ANI) and Ancestral South Indians (ASI). While the ANI ancestry is strongly related genetically to Central Asians, Caucasians and Europeans, the ASI ancestry derived from within the subcontinent. This finding in genome analysis corroborates with the evidences from archaeology and linguistics, that there was a mixture between ANI and people from the said regions. 

[There happened mixtures between ASI and ANI as well, but endogamous marriages became the order of the day when the caste system came into vogue precluding any further admixtures.]

Clearly, the etymological similarities between the said language families strongly suggest a single single linguistic superfamily (Proto-Indo-European superfamily) from which civilizations diverged. So it is certain that there were some ancient populace who migrated and somehow some of the words still managed to survive the language erosion. 

[The term Indo-European was first used by none other than Thomas Young, the British Polymath, famous for his double-slit experiment that foxes our ordinary minds!] 

The most accepted opinion is that the early linguistic ancestors migrated from the Pontic Caspian steppe, somewhere near Ukraine, to populate more southwards. There is another postulate that the early migration took a northward route, towards Europe.

But is there any proof that these ancient people really traveled or migrated? There is, indeed! Not only the similarities in language, there are also other clues that prove that this migration really happened. It is bolstered by archaeological, ecological, genetic and anthropological evidences. Though it is innate human nature to forage and advance just for the sake of adventure, the early migration may have arisen out of necessity. The early hunter-gatherers may have moved to a favorable place where farming and agriculture was prevalent, so that they could feed themselves and their cattle and horses. Perhaps a harsher winter in Europe forced these population to leave their original homeland (Urheimat hypothesis or the primary homeland hypothesis).

Consider the Gundestrup Cauldron (below) adored as a beautiful example of Celtic art, discovered in Denmark in 1891 and was thought to date back to about 100 BC. 

The horned god, sculpted in the cauldron, looks very much like the seal of Shiva/ Pasupati icon of  early Indus Valley Civilization (below), which dates back to about 2000 BC. 

There are other artefacts of proto-Indian-European (PIE) religion that suggest the linkage of ancient Indian items to that found in Europe.

Of all the possible theories that explain our common ancestry, the most interesting perhaps is the Genetic theory. 

There are 46 chromosomes in humans. 22 pairs of autosomes and two sex chromosomes: XX in females and XY in males. In addition to these strands of DNA that these chromosomes contain, there are mitochondrial DNA (mtDNA) that also contains the 'four letters' (ATGC) of the nucleotide alphabetic lexicon. What's interesting about these mtDNA strands is that they are inherited "exclusively" from the maternal side.

So it's certain that migration of population did take place but in which direction? The Aryans migrated from Europe or the other way? I'm sure that if you have seen the 2 pictures above and noted their dates as well, you've already drawn your conclusion!

We will next discuss about the faint 'possibility' of a plaussible "Aryan Invasion Theory" in our next blog post. Till then hang on! 

Special Reference:
https://www.rbth.com/blogs/2014/11/01/sanskrit_and_russian_ancient_kinship_39451

["The Sanskrit language, whatever be its antiquity, is of a wonderful structure; more perfect than the Greek, more copious than the Latin, and more exquisitely refined than either":  (William Jones, Philologist)]

Published on 30/06/2018, last updated on 02/03/2025

tags: aryan invasion theory, genetics, evolution, DNA, archaeology, cognates, James Bond, Specter

A Tale of a Microprocessor, RISC and a Few Loops of miRNA

The word ‘microprocessor’ is generally used to designate VLSI and SLSI (Very/Super Large Scale Integrated circuits) devices which accept, decode and execute instructions presented in binary coded forms. They may be called the heart of the computer. RISC (Reduced Instruction Set Computer), on the other hand, is a type of microprocessor architecture that uses a simplified, yet highly-optimized set of instructions to deliver good performance. However, like ‘cell’ and ‘nucleus’, they too have been adopted in biology, and not without reason!

Proteins are essential for cells as they perform various functions as enzymes, ion channels, receptors and so on. They are manufactured in the ribosomes, organelles present in the cytoplasm, under the instruction of messenger RNA (mRNA). This instruction code is encoded in the sequence of nucleotides that make the mRNA molecule. However, the sequence of nucleotides in mRNA is dictated in turn by the DNA that is present in the nucleus. Messenger RNA carries this message from the nucleus into the protein production units. But what would happen if we interfered with the ‘message’?

RNA interference (RNAi) would occur affecting the regulation of gene expression. Micro RNAs (miRNA) are one of the small RNAs that regulate the expression of protein-encoding-genes, after the mRNA strand has formed. miRNAs have partly or fully complementary sequence to one or more mRNAs. This enables them to latch on to the mRNA molecule masking the ‘instruction codes’ in the mRNA strand, interfering with protein formation (translation). In other words, the gene has been silenced!

miRNAs are first transcribed from DNA by the enzyme RNA polymerase II into primary miRNA (pri-miRNA). pri miRNA is then cleaved by another enzyme, RNAse III, called Drosha, into precursor miRNA (pre miRNA) (see the picture on the left). However, Drosha (an RNAase III endonuclease) is assisted by Pasha (partner of Drosha), another enzyme, in this task. Later, it was found out that these two resided in a 500 kilo Dalton complex, called the microprocessor (micro RNA processor). So far, all these have been happening in the nucleus of the cell. The pre miRNA then moves into the cytoplasm through the exportin 5 pathway. Next, Dicer, another RNase III endonuclease, makes a mature miRNA duplex, which is then ‘uploaded’ into a complex called RISC (RNA induced silencing complex). RISC then prevents translation of the mRNA strand, as the ‘partially’ complementary miRNA strand interferes with the translation of the mRNA molecule into specified amino acid sequences can not occur. We can compare complementarity of nucleotide bases in terms of a pair of gloves and its corresponding fingers. The information of the gloves' coordinates gets obliterated by the occupying fingers. This RISC dependent mechanism occurs in parts of the cytoplasm, called P bodies (‘p’ for processing).

RNAi is very important for plants as they lack an immune system. Invading organisms can not dictate foreign protein formations as their RNAs are destroyed, not merely inhibited, as is usually seen in higher animals (animal miRNAs exhibit only imperfect homology to the mRNA in contrast to plants, and thus they only inhibit translation). Some of the tumor suppressor genes inhibit tumor formation by the action of miRNAs and not through protein formation. In humans, exploiting RNAi may be a useful tool in combating diseases such as cancer, AIDS etc. So it remains to be seen whether the microprocessor can bring a revolution in medicine and research as its counterpart in electronics did in the field of computing.

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Reference: Saumet, A., & Lecellier, C. (2006). Anti-viral RNA silencing: do we look like plants ? Retrovirology, 3 (1) DOI: 10.1186/1742-4690-3-3
Processing of primary microRNAs by the Microprocessor complex. doi:10.1038/nature03049
Wikipedia
The Macro World of MicroRNA (pdf)

An Overview of Gene Therapy

Ashanthi, a four year old girl, was suffering from an immune deficiency disorder called SCID (Severe Combined Immune Deficiency). Due to the lack of a healthy immune system, she was susceptible to infections even from germs which otherwise would not affect healthy persons. She was confined to her room, met no one outside her family, and had to take heavy doses of antibiotics to fight the microbes on behalf of her dilapidated immune system. A team of doctors from the National Institutes of Health, in the United States, drew blood from the patient’s body, and separated the WBCs (white blood cells; cells which fight infections). They then cultured the WBCs, inserted the missing gene and then infused the blood back into Ashanthi’s bloodstream. The girl survived, she no longer lived a recluse life and antibiotics were no longer a ritual. That was the first approved gene therapy (ex vivo, as the engineering was done outside the body) procedure carried out in a human.

Gene therapy is the procedure of replacement of faulty genes (nucleic acid sequences) by healthy ones. Frequently, a normal gene is added to an existing faulty allele, rather than a replacement of the gene at fault. Genes consist of stretches of deoxy-ribonucleic acids (DNA). The nucleic acid sequences in the DNA dictate the formation of proteins via the mediation of ribonucleic acids (RNA). Information contained in the DNA is passed on to the RNA by a process called ‘transcription’, which occur in the nucleus of the cell. RNA then goes to the cytoplasm of the cell where it forms a protein, in a process called ‘translation’; the functional product of that gene, its spokesman! The DNA sequence determines the sequence of amino acids in the protein, which is important in that any mistake in having the right amino acid in the right place may yield a non-functional protein with an abnormal configuration. Thus, an abnormal DNA sequence might (not always) produce a non functioning enzyme (a protein), causing diseases of immunity, metabolism and cancer.

We can ‘insert’ a normal functional gene into the genome containing an abnormal one; exchange an abnormal gene for its normal counterpart by homologous recombination; we could even ‘regulate’ the ‘expression’ of a particular gene. Inherited genetic diseases like thalassaemia, sickle cell anemia and cystic fibrosis could best be tackled by manipulating the ‘germ cells’ (sperms and ova) and this not only would ensure that the progeny was healthy but would also be passed (this new gene) onto the next progeny. Such heritable ‘germ line therapy’ despite sounding promising, is prohibited due to ethical concerns and the lack of expert technical knowhow. ‘Somatic cell gene therapy’, the gene therapy practiced these days, however, is not heritable.

Now that we know the basics, we should find a suitable carrier (vector) to deliver the goods inside the cell. Viral vectors are the most commonly used. Retroviruses, for example, take with them 2 identical copies of single stranded RNA (ssRNA); an enzyme called ‘reverse transcriptase’ and ‘integrase’, another enzyme, when it enters a cell. Reverse transcriptase or RNA dependent DNA polymerase converts the RNA sequences into DNA. The double stranded DNA then integrates with the host genome by the mediation of ‘integrase’. A therapeutic gene could now express itself in the form of a usable protein, via the integrated viral genome. Since viruses may cause disease, researchers must ensure that the disease causing genes of the virus are deleted. For example, AIDS is caused by a retrovirus (HIV). Another cause for concern is that retroviruses integrate randomly in the human genome. If they sat close to a proto-oncogene, or in the middle of a tumor suppressor gene (this might disable the suppressor gene), it might cause cancer.

Adenovirus is another option. A double stranded DNA (dsDNA) virus, adenovirus, does NOT integrate with the host cell, hangs free in the nucleus and just carries out transcription. Frequent administration is necessary, as the gene does not replicate with the host cell. Adeno-associated virus (AAV), an ssDNA virus, may also be used as a vector. The recombinant type (rAAV) carries NO viral gene & does NOT integrate. But they can infect quiescent (non-dividing) cells, hence may prove useful in neural/neurodegenerative diseases.

Non viral vectors include:
Naked DNA: Transfection (using phosphate-DNA mixture), Electroporation (use of electrical pulse for better membrane permeability), Sonoporation (using ultrasound for facilitation of DNA delivery), gene gun (DNA coated gold nanoparticles ejecting out along with high velocity gas) are some techniques for delivering DNA fragments.
Oligonucleotides: Antisense nucleotide sequences for the target gene. Being antisense, the nucleotides will latch onto the sense strand, just like the opposite poles of a magnet, thus preventing its translation. Fomivirsen is one such drug which is used in cytomegalo virus (CMV) retinitis. 
Short interfering RNA (siRNA); Small nucleotide sequences which tell the cell to cleave faulty mRNA.
DNA-lipid complexes (lipoplexes): here the DNA molecule is covered with an arrangement of lipids in the form of a micelle. Using a nonionic surfactant such as Tween 80 in addition, gave a better yield.

The challenges are still great. Our immune system and the genome do not take these pieces of DNA easily. For example, the gene transfer frequency (in hematopoietic stem cells of dogs and monkeys) for adenosine deaminase, the deficiency of which causes SCID, was only 3%. Still scientists hoped that the healthy cells would outgrow diseased cells as they had distinct survival advantages. But the efficacy of delivery didn't improve.
As of today, most major trials on gene therapy are on pluripotent hematopoietic stem cells (PHSC) and cancer cells. It is only natural to assume that genetic manipulations on blood stem cells (PHSC) would cure a variety of diseases affecting the blood cell lineages. And the quest goes on.

1. Mark A. Kay*,, 2. Dexi Liu, and, 3. Peter M. Hoogerbrugge (1997). Gene therapy PNAS , 94
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References: Gene therapy
Gene therapy PNAS November 25, 1997 vol. 94 no. 24 12744-12746

The Unsung Hero (ine) of Genetics

We all credit Watson and Crick for their discovery that the DNA molecule was arranged in a double helix pattern. But how many of us know about this charming and intelligent lady, Rosalind Franklin, who made their discoveries much easier, by 'providing' them with the distinctive diffraction X-ray photograph, termed 'Photograph 51'?

Working in scientific arena was traditionally a man's domain then, and women were frowned upon. Naturally, as expected, she also had been subject to much harassment by her male colleagues. At the same time, she also used to make fun of her male colleagues.

While working on Signer DNA (DNA molecules, extracted from the thymus gland of calf; used for their distinctive X-ray diffraction pattern ), at King's College, London, she found out that there were two forms of DNA; a 'wet' form (B-DNA), that was longer and a 'dry' form, that was shorter. They continued with working on the wet forms.

Watson and Crick were also behind the same trail of determining the nature of DNA, but they were far behind any possible breakthrough. They did not even know about Chargaff's Rule, that stated that for every Adenine molecule, there was an equal number of Thymine molecule, and the number of Cytosine molecules were equal to that of the Guanine molecule (A=T, G=C). By sheer luck, Watson chanced upon Photograph 51 (picture shown here), 9 months after it was kept in a vault by Rosalind. He was quick enough to deduce the 'double helical' structure by intuition and reasoning. The 'x' like speckled banding had enough tell-tale signs.

Watson, Crick and Wilkins were awarded the Nobel Prize in Physiology or Medicine, in 1962, for their discovery about nucleic acids (not exclusively for DNA). Rosalind was long dead by then. She died of ovarian carcinoma in 1958, possibly due to extreme radiation exposure. It is also true that some of her own family members also died of cancer and that cancer incidences were particularly high in Ashkenazi Jews, which she was. Whatever the cause of her death were, the contribution she made toward the understanding of DNA structure, have certainly paved the way for modern genetics. In our minds, she will continue to dwell forever.

Hayflick limit, Telomere and Aging

We keep our pens capped so that the pen tips don't get damaged and the ink doesn't dry. Similarly, the DNA in the chromosomal ends are 'capped' by protective molecules, called the telomeres. Telomeres consist of about 1000 repeats of 'TTAGGG" sequence, where T stands for Thymine, A for Adenine and G for Guanine. All these are nitrogen containing molecules (nitrogenous bases).

During replication, the double helical DNA molecule is first unwound by an enzyme called helicase, it is then split by another enzyme, gyrase (=type 2 topoisomerase: it does it by un-twisting the DNA helix in the opposite direction, by introducing negative supercoils, and then makes a nick in one DNA strand, so that it can be copied), and only after all this can DNA polymerase copy the DNA template.

But after each replication, some of this telomere, the so called 'non functional strand' of DNA, is lost. This occurs, since DNA polymerase can not copy one end of the DNA (the 5' end). Thus it has been seen that after about 50 cell divisions, the cell dies (Hayflick limit). When the telomeres are shortened up to a certain limit, the cell sends a signal to p53 protein (known as the guardian of the genome), and the cell then stops dividing and goes into 'replicative senescence'. Stem cells, germ cells and cancerous cells can bypass this limit by the help of telomerase, an enzyme capable of replenishing lost telomeres. Telomerase is actually a reverse transcriptase (normally DNA generates RNA and this process is called transcription. When RNA generates DNA it is thus reverse transcription. In AIDS, another reverse transcriptase wrecks havoc). Telomerase (hTERT= human telomerase reverse transcriptase) and a RNA template (template=dice, just like webpage templates) is enough for telomere reconstruction. However, the idea of restoring telomerase for cellular 'immortality' is not assuring enough as immortality in cells other than stem cells or germ cells means malignancy.

Some substances like alpha hydroxy acids (AHA) glycolic acids, when applied on the skin (face) promotes cell division, thus prompting the growth of new cells, the facial skin gets a cosmetic lift; but due to enhanced cell division, after a certain stage, cells approach the Hayflick limit, and the skin gets aged and wrinkled.

Thus telomerase manipulation should be cautiously weighted against its accompanying risks.

Related article: Aging: From a General and Evolutionary Perspective
Aging, Mitochondria and Free Radicals

Chasing The Evanescent Electron

Come April 2008, I will become older by one year. My physiology will age and decline. There may be photoaging of the skin, formation of cancers and many more. All the above and more can be attributed to the formation of free radicals, pyrimidine dimers etc.. They in turn are caused by wayward and unpaired electrons impinging on other molecules. But spotting these electrons, in real time, had proved elusive. Now the time has come to catch 'em red-handed, though for a very very minute period.

The strong electrical field of a potent Laser, can make electrons in an atom, jerk off briefly. We know that light is a electro-magnetic wave. This phenomenon, called tunneling, is akin to bobbing of a float in water, up and down, due to the propagating wave (laser or light is electromagnetic wave), when an object is thrown in it.

Formation of 'holes' and electrons in semiconductor chips, photoelectricity, pyrimidine dimers, free radicals may be explained; even new hypotheses in vision physiology may be put forward, when the technique is mastered. The electron transport chain in the mitochondria may reveal new light, and many other vistas stand to be explored, as a byproduct of this phenomenon.