लोकहो, काही दिवसांपूर्वी मी या ठिकाणी अधिजनुकशास्त्रावरील लेखावर बरीच प्रदीर्घ चर्चा झाली. या चर्चेत मी डॉ० जगन्नाथ दीक्षितांचा उल्लेख केल्यामुळे या चर्चेचा दूवा डॉ० दीक्षिताना पाठवला होता (ते या समूहाचे सदस्य नाहीत). ही चर्चा वाचल्यावर त्यांच्याकडून आलेले विस्तृत उत्तर मी जसेच्या तसे पुढे देत आहे. मला आणखी काही गैरसोईची सत्ये सांगायची होती पण ती नंतर कधीतरी... -- युयुत्सु ON MY EPIGENETICS POST COMMENTS RECEIVED FROM J.K.Dixit, M.D: Rajeev Upadhye, asked me to look into his write up for this forum on epigenetics. This response could be lengthy and I have to break it up in parts as I do not know limits of length of comments. First, I want to clarify that Rajeev does not make a dime from the sell of our upcoming book in Marathi if you buy this book or not. The whole project is charity funded by Dixitfamily.com His main intention is to spread the state of the art knowledge to 130 million Marathi speaking people all around the world otherwise who have no decent access to such information. Rajeev Upadhye’s intention for this post is to educate and promote healthy feedback and discussion and not argument or attack or confrontation. There has been unfortunate and erroneous use of terms such as “ किडकी प्रजा” “किडकी बीज “ and complete derailed discussion about “mutations,” “adaptations,” etc. which have no connection to “epigenetics.” I also feel sorry for the mudslinging which took place here and criticism received by people like Dr. Subhod Khare ( If I am correct, he is the same fine physician who used to be on Yahoo Chitpavan forum) etc. When India produces one million metric tons of garbage DAILY and industrial waste and this is mostly concentrated in large cities in India, and Mumbai and surrounding population exceeding 30 million human beings his criticism is not totally out of place signaling out cities such as Mumbai. Delhi etc. (Delhi being one of the top worst polluted cities in the entire South East Asia.). India adds currently between 60,000 to 100,00 newborns DAILY and where only 15 to 20,000 or less than one third people die daily. Some statistical numbers showing pollution more in the rural side than urban side is nothing more than delusional fabrication when one considers pollution in the air, water, food, etc. As they say, statistical numbers don’t lie, statisticians and politicians do. Upadhye’s claim has some validity that where population density is less as on rural side as compared to densely populated urban areas net effect of pollution factor could negate or dilute some epigenetic damage on rural side. Mumbai being heavily covered by tar and concrete and at the sea level does not drain waste water and rain promptly and pollution in water and diseases linger longer (as recently happened in Houston). Estuaries contaminate fish, sea food, locally grown produce, etc.etc. Every human being as you will see below more in detail discussion is gifted with a combination of “good” or protective and “bad,” harmful genes in our total genes in humans around 25,000. As he shows effect of congestion, air pollution, water pollution, contamination of drinking water with waste and sewer, water shortage, rampant infectious diseases ( Just for one example,India has over 100 million TB patients and several million are drug resistant and active open cases), lack of adequate nutrition missing key nutrients, lack of sanitation, corruption, lack of opportunity for skilled people due to quota system, longer exposure to traffic congestion and leaded fumes, lawlessness, massive poverty, lack of education and hygiene, religious intolerance, poor health care, lack of morality, ethics, stresses of modern life, job pressures, and dwindling resources have a devastating effect on your genome which results in very damaged “epigenome,” This results in activation of several “bad,” and “mean” genes” for self preservation at any cost This “pre programmed” bad epigenome is handed down by such similar experiences of your grandmother to your mother can bring out worst in you, such as affecting complex behavior such as lying, cheating, lack of ethics, lack of morality, lack of compassion and empathy, low birth weight, obesity, diabetes, making you more prone to harmful inflammatory and neurodegenerative diseases, heart disease, high blood pressure, cancers, arthritis, etc. later in life. (Actual damage to your genome is another story with lethal mutations, etc.) Genetically most important person for you is your maternal grandmother and all previous grandmothers, all the way to about 6000 of them from the birth of humanity with their life’s cumulative effect and SNP’s. Most fascinating issue in medicine currently is NOT genetics, but "epigenetics," Doctors have always wondered about "heredofamilial diseases or the characteristics. What it means, you see certain characters in family members or related members or diseases, but there is no definite identifiable gene or genes in our over 25000 genes in 37.2 trillion body cells. Then how do these characteristic get passed on ? How certain diseases arun in some families. How a son of great musician becomes a great musician when there is no genetic basis or they are separated at birth and there is no parental “acquired” influence? That happens by epigenetics. There are the "switches" to turn your good or bad genes off. The term used in Rajeev Upadhy’s write up "शेपट्या" should be replaced by “खुंट्या” these are the sites directly on DNA where methyl or acetyl groups attach as to turn on or off switch or in the matrix or chromatin material on histones where HAT / HDAC group of enzymes either turn on or off genes. Every second of your life about 1 billion times these are either turned on or off. Some are switched on for few seconds, some for life etc. For example, genes which control your breathing or heartbeat are active all the time from birth. But say when you put “misal pav,” in your mouth saliva secreting glands and genes producing them are active only for a short time. ( Read more in our upcoming book for lay people is coming out in 2018 first in Marathi and in English). Our aim is how to help you by diet, exercise, supplements, Pranayam by “Dixit Protocol,” to turn your good genes on and turn bad off which cause you diseases such as arthritis, Alzheimer's, cancer, etc. so you don't need any treatment. When your mother was born her ovary containing one of the the "ovum," from over 200,000 ova, matured and which eventually became "you" was already formed. So technically your grandmother was your mother who assembled your half or 1.5 billion genetic letters perfectly. . Human females do not produce new eggs after they are born during their entire life. Although some primordial “stem cells” are also found in ovaries, but they are inactive unless ovaries are injured or cut by surgery, etc. (In males this is different - who produce new sperms rest of their lives, and their epigenetic role is limited as you can read here later.). So technically your "genome" was formed by your grandmother. She also turned few genes on or off (like a pre loaded software) and handed down to your mother, genetic autosomal influence from from x chromosome from your father's mother (in case of females) or from powerful SRY gene from Y chromosome for males is less than 10 % and down the road influence is mostly inhibitory,( by the powerful SRY gene on Y chromosome in males is described in the book). It is still significant and many genes may be non dominant and unexpressed, only if they come in contact with some similar recessive genes, then they will be expressed. Your grandmother's life and her experiences matter because just like "karma," these are now shown to be passed on next generations by epigenetic modifications. So if you take about 8 moths from your mother’s age and the year when she was born , you were or half of your genome in the form of the ovum primary oocyte to Primordial follicle was present on this earth. So, until you were born, it grew very little but it did receive the hits and some damage from free radicals, toxins, etc., just like other mothers normal cells and stem cells, etc. until it was fertilized ( but it was not like it was frozen and preserved, so its aging like any other biological tissue is real). If you believe in concept of soul, then your soul also began then - sperm probably has very little contribution to the soul or your cosmic connection to the universe as described later. Your mother's womb is like a "3 D printing machine" once the instructions for you- all 1.5 billion pairs of DNA and countless epigenetic markers fabricated by your grandmother were handed down to your mother ( and other 1.5 B received from your father with a powerful "master switch gene" SRY ), the printer went in action , over the course of next 9 months- your mother printed about 2 to 3 trillion of your cells when you were born from the instructions she received ( over 86 billion were just brain cells ,and other nerve cells totally about 100 billion nerve cells at birth, and another 100 billion were heart cells, reproductive DNA of these cells unlike other cells was sealed tight shut, so it will never open and these cells will only grow, but never will reproduce like other cells). This 3D printer is however, not water tight- some of the mothers "adult" cells escaped from placenta and anchored in your body forever, but never your father's cells are inside you- confusing your immune system for the rest of your life. She also gave from her milk your very specific protective "probiotics" or gut lacto bacteria and other 20 varieties to colonize your inside and outside of the skin once you were born to boost your immune system (Fetal skin and gut is sterile in the womb). Book describes why certain ethnic group likes certain food, or why in the world mostly Indians like Indian food and not others, or why everybody in the world likes- Pizza. An average 70 kg. person has about 37.2 trillion cells in the body, male or female. Each cell has over thousands of life force giving energy producing bodies called "mitochondria," Each and every cell of your body's those mitochondria are marked and has a label as " manufactured by your mother" - MtDNA - your mother's own signature) Markers of your both mother and father like names are inside the nucleus as x and Y chromosomes, again X chromosome is way larger and is in bold type and caries over 3000 genes.) Actually your first starting point and base stock for your body is cytoplasm of the ovum called ooplasm. All your future ribosomes, transfer RNA (tRNA) and messenger RNA (mRNA), mitochondria come from mother only (That superb athletic endurance and performance unlike you or me for say for Sachin Tendulkar comes from the energy producing mitochondria shaped and designed by his maternal grandmother). Ooplasm given by our grandmother contains all the Golgi bodies, endoplasmic reticulum where each and every lipid or protein, or secretion, is formed in your body is shaped by your grandmother. Not to mention compared to the head of a sperm which brings paternal genes into the nucleus ovum is the main component for your body, and ovum is about 30 times larger than the head of the sperm. In fact this is the only human cell which can be seen by the naked eye. This ooplasm plays a central role in forming the paternal pronucleus, and subsequently even in regulating the expression of paternally inherited chromosomes by epigenetic changes. When sperm enters the ovum, all of father’s mitochondrial DNA is destroyed, all paternal mitochondria are killed. 70 % histone or spools on which father's DNA is wound down is destroyed (where epigenetic switches from fathers side are located). After fertilization in the embryo once again all the epigenetic switches from father and mother are removed, but most of the maternal switches are reintroduced mostly by the effect from ooplasm. If there is universe, soul, God, etc., then your existence and connection to it is only through your mother. If there is no mother - you do not exist (At least that is the way it is for now -science can change that in future and your manufacturing label could change). Evolutionary father only adds little genetic variation and sturdiness, but is not necessary for many species and parthenogenesis is widely practiced in the nature. So practically your mother is God, father may be a demi god, and your connection to this universe is only through your mother and your children. So treat all of them well with respect. So, there is some truth in the religion of " ancestral worship" practiced by some Chinese, Vietnamese, and Koreans. They do not have Indian style small shrines ( Devaghar) for worship of the gods; in their homes , but have "Jesa altar" for the veneration of the dead. Curiously, in Vietnam there is no practice of celebrating anybody's birthday, but they celebrate and pay respect to the death anniversary each year for their father and mother, mostly for their mothers. When a teen or adult child is badly hurt- it hurts and upsets mother more than the father - because mothers actually have few of the child's cells in their body (and so does the child) a literally cellular" connection and this may respond to the stress of the child inside the mother as child’s own cells. Recently, children’s brain cells (male as well as female) have been found in some 70 -80 years old mother’s brain in autopsy after death !! Why concept of our self, self awareness, self identity in group ours and others, development of mind, consciousness,/ soul/ - connection to God if there is one or many - or our cosmic connection to universe comes from the ooplasm (cytoplasm) of the ovum given by our mothers - Not from the father is described in the book . The reason we know this is from studying even tiny unicellular organism such as bacteria or amoebas who have very primitive DNA, have no sensory system, or nerves, but they run away from acidic water, heat, light, toxins, etc. They are not alone, they know where other bacteria are. They communicate by sending and receiving molecules from their walls and these walls are made by your grandmothers. The reason you or your fertilized ovum is 30 times larger is that during first about 16 divisions of the ovum (when basic cells of your heart, brain, skin etc. are now finalized) , no new ooplasm is manufactured, All the energy is used to duplicate your genome. So all the basic “juice,” to each and every cell in the body which later is just duplicated in all of your 37.2 trillion cells comes from your grandmother -mother connection. Receptors on the outside of each cell wall are shaped by your grandmother कोनाडे or खुंट्या where molecules dock- - they decide how your body will respond to stress, nutrition, drugs, etc. Their function based on your total genome -epigenome from your father and mother can only go up or down (brake or accelerator) - but the basis cannot be changed ( आडात नाही तर पोहऱ्यात कसे येईल ) Interesting thing is -that this cellular induced and evolved "identity" ( me or self) in the human brain is located at a different center and place in the brain than given identity, such as say your given name " Rajeev" is located at different place in the brain. Bottom line; learn more about your maternal grandmother and events which shaped her life, as emotional part of your brain is mostly inherited. Inconvenient truth which Rajeev barely eludes to is actually- epigenetics supports the concept of “caste,” (not caste system- which is a human creation of unjust discrimination based on caste). Because although all human beings on earth are genetically 99.5 similar - that difference of 0.5 % SNP- single nucleotide polymorphism and epigenetic changes make us all unique. So all human beings are epigenetically different. Since mother and her mother and her mother can pass down non genetic good/or bad characters down the progeny (पूर्व पुण्याई or पूर्वजांची पापे ) this - is the basis of the term “caste,” where a certain ethnic group shares some common good or bad non genetic features. How countries like India will swallow politically and socially such unpalatable truth is a very troubling question. In the book, about 300 pages you will read in Marathi even if you inherited bad “epigenome” - how you can learn to turn on your good genes and turn off bad ones. Book contains What can you do about your diet, exercise, key nutrients, or what are newer advances in simple ancient Indian technique such as by Pranayam which can change your life. Book contains several updated chapters written by (JD) in Ekata in US over the last 10 years , and recently jointly written with Rajeev Upadhye.