From the Desk of Coordinator, Bioinformatics Centre


Nature Vs Nurture –

                      The Dancing Genes


       Elucidation of DNA structure as right handed double helix by Watson and Crick in 1953, who were awarded Nobel Prize in 1962, was a mile stone in the era of modern biology.  Human Genome Project was conceived in 1984, started in 1990 and completed in 2003.  Two teams were involved namely

1.         International Human Genome Sequencing consortium (IHGSC) headed by Francis Collins involving research groups from USA, UK, France, Germany, Japan and China and

2.          Celera Genomics - private company at Maryland led by Craig Venter. Human Genome has 3 billion base pairs with 34000 genes coding for proteins (less than 3% of total DNA).  More than 97% of DNA is non coding (so called Junk DNA) involved in regulating gene expression during development, differentiation and adaptation to environment.

                   Gene is DNA, carries genetic information from one cell to the offspring.  It determines morphological, chemical and metabolic characteristics of individual cell or organism.  Mammalian cell possesses about 1000 times more genetic information than does the bacterium E. coli. Humans have same DNA to the extent of 99.9%. Fraction of a percent gives individuality (intelligent, dullard, aggressive, mild, normal, disabled etc.).  Further Humans share 98% DNA sequence with monkeys, 57% with cabbage.  Only 300 genes of humans had no recognisable counter part in the mouse. Humble weed plant, Thale cross (Arabidopsis thaliana) carries 30% of its genes with notable similarities to humans.  The commonness of some genes shows subtle connection between all living systems.

            After decoding Human Genome, there is considerable awareness and expectation in the public.   It is not a surprise to see the scientists, scientific journals and magazines with sensational news on Genes.  Geneticists, Psychologists, Psychoneuroendocrinologists are excited and actively involved in Genomic Research. Number of Genes associating with behaviour, emotions and feelings have been often reported.  To name a few Gene NeuroD2 with dare devil behaviour, CYP2A6 with addiction, ISIG2 with obesity, DRD4 with sexual desire & performance, Variants of DRD2 with anorexia, AVPRIA and SLC6A4 with creative / dance performance.  God Gene - VMAT2 with human spirituality, GCH1 with chronic pain, TREK – 1 with happiness, BDNF with depression,  gpr 54 with puberty, and 10 Genetic mutations in SIR3, SIRT1, IGF - 1, Lamin A (Pr) etc with longevity (life span).  Presence of a particular Gene is not sufficient.  Its expression is important.  Genes may be Constitutive Genes (house keeping genes) for synthesis of proteins required for the cell, expressed at more or less constant rate in all the cells.  Some genes are regulated (induction or repression) by various molecular signals.

            Gene Regulation in Eukaryotes is more complicated and is brought out by several mechanisms like gene amplification, gene rearrangement (light chain and heavy chain Ig), small RNAs as enhancers / silencers and deacetylation of histone protein, methylation of DNA in inactivation of genes.

            Although > 99% of human DNA sequences are the same across the population, difference between individuals are largely due to SNPs (Single Nucleotide Polymorphisms). About 3 million SNPs are believed to be present in the Genome.  It involves the replacement of one nitrogen base by another (C→T or A→G etc).  Sickle cell anemia is due to a single nucleotide change (A→T) in the β-globin gene of hemoglobin. SNP maps of human genome can help in determining the likelihood of some one developing a particular disease (cancer, diabetes etc.).  SNP map project is of interest in pharmocogenomic studies (effect of drugs in individuals) and hence number of drug companies have funded to find new SNPs. Studies at University of Pennsylvania on Gene activity of 4197 genes in white cell lymphoblostoid, showed Europeans and Chinese expressed 939 at significantly different levels while Europeans and Japanese expressing 756 differently.  This is due to SNPs showing how tiny changes in the basic DNA code can significantly affect the expression of whole genes.   Populations that differ in their susceptibility to diseases such as type 2 diabetes and high BP carry different SNPs and the specific genes may be targeted with drugs.  Gene sequences alone do not tell the whole story.  Svante Pääbo (Director of Evolutionary Genetics, Germany) observed differences in gene expression by measuring mRNA in autopsied brains, possibly playing a role in creating the gap between the chimp and human brains.  Pääbo recently began a project to breed mice laced with human – specific genes involved with brain growth and development.  The first of these humanized mice are now being born in Germany (Discover Dec, 2006).

            Epigenetics is the Study of heritable changes in gene function that occur without a change in the DNA sequence.  Epigenetic mechanisms such as DNA methylation, histone acetylation, RNA interference, Gene imprinting and silencing play important role in gene activation and inactivation and in phenotype transmission and development, the so called epigenetic inheritance.   A simple environmental effect could switch genes on or off – and this change could be inherited. The idea that inheritance is not just about which genes you inherit but whether these are switched on or off is a whole new frontier in Biology. Genes and the environment are not mutually exclusive but are inextricably interwined, one affecting the other.  ‘Incorrect’ epigenetic changes to tumor suppressor genes and oncogenes are some of the first steps in cancer initiation.  Studies at Mount Sinai School of Medicine on the effect of stress on pregnant women who were inside or near the World Trade Center during tragic events on September 11, 2023 suggest that stress effects can pass down generations.  Another study at Washington State University points to toxic effects, causing biological changes in rats exposed to pesticides persist for at least four generations. 

            Different studies brought a paradigm shift in scientific thinking how life style and family relationships affect individuals and also their children and grand children in decades to come.  If you liken the genome to the hardware of a computer, the epigenetics is the software. There are number of research studies using Holistic Medicine for prevention and management of cancer.  Studies at McGill University showed that nutrients and supplements changed genetics by switching on or off certain genes in rodents.  L-methionine, a common amino acid and food supplement, when injected into the brains, the amino acid methylated the glucocorticoid gene, and the animal’s behaviour changed.  Green tea helps in silencing HER-2 genes that fuels breast cancer in some women. Turmeric suppresses genes (COX-2) that ratchet up inflammation.   Nutrition and Genetics is catching up.  Within a decade, doctors will be able to take genetic profiles of their patients, identify specific diseases for which they are at risk and create customized nutrition plans accordingly.

             Nature Vs Nurture has been debated often.  DNA is not destiny.  “Gene as fate” has been conventional wisdom.  Through the study of epigenetics, that notion may be proved outdated. Unlike genetic mutations, epigenetic changes are potentially reversible by switch on and off mechanisms (methylation or demethylation).  One epigenetic drug, 5-azacytidine has been approved by FDA for treating myelodysplastic syndrome (pre leukemia). Similarly studies on development of drugs for other cancers are under testing.

            Epigenetics introduces the concept of ‘free will’ into our idea of genetics.  Epigenome can change in response to the environment through out an individual’s lifetime.  Now everything we do – everything we eat or smoke can affect our gene expression and that of future generations. The environment (diet, behaviour, family relationship, lifestyle and surroundings) has a role to play in changing our genome, bridging the gap between social processes and biological processes.

            In this scenario definition of Holistic Living in the recent Symposium held at Sevagram may be of interest. Holistic Living is defined as Simple, spiritual, purposeful, peaceful and productive living with moderation in food intake, adequate exercise and positive thinking and attitude to life.  Holistic Living is an art of living in harmony with nature and concern to the whole universe.

March 15, 2007

Prof. B. C. Harinath