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A little about how DNA works

A little about how DNA works. David Sloane, MD Special Studies, HGSE Brigham and Women’s Hospital Harvard Medical School des770@mail.harvard.edu. Nature and Nurture. What is meant by “Nature”? Is it the same for all human beings regardless of space, time, and context?

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A little about how DNA works

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  1. A little about how DNA works David Sloane, MD Special Studies, HGSE Brigham and Women’s Hospital Harvard Medical School des770@mail.harvard.edu David E. Sloane, MD

  2. Nature and Nurture • What is meant by “Nature”? Is it the same for all human beings regardless of space, time, and context? • What is meant by “Nurture”? Is it the same for all human beings regardless of space, time, and context? • What is epigenetics? David E. Sloane, MD

  3. Overview • What is genetics? • What does DNA have to do with genetics? • What is DNA? • How does DNA copy itself? • How does the information in DNA get expressed? • What are gene regulatory networks? • What is epigenetics and how does it work? • What are some DNA tests germane to mind-brain research? • Let’s have a (nice) fight…. David E. Sloane, MD

  4. References • All colour images and tables are from Watson et al, Recombinant DNA, 3rd Edition, 2007. • Except that some are not: they’re from Korf and Irons Human Genetics and Genomics 4th Edition, 2013. • Original paper quotes and figure are from Watson, JD, and Crick, F; Nature, 1953. David E. Sloane, MD

  5. What is genetics? • What is a trait? • An observable characteristic in an organism, such as seed colour. • What is a gene? • A factor that determines a trait David E. Sloane, MD

  6. What does DNA have to do with genetics? • Deoxyribonucleic Acid (DNA) is the substance that encodes genetic information; “The genotype is the complete genetic composition of an organism.” (Recombinant DNA 2007) • Its physical expression leads to the appearance of traits in an organism, which is called the “phenotype” • Example: a stretch of DNA encodes instructions for the construction of a protein that determines eye colour (say, brown). Those DNA instructions are the genotype. The actual eye colour is the phenotype. • A ridiculously overextended metaphor: the cookbook. David E. Sloane, MD

  7. What is DNA? • An un-branched polymer of Nucleotides What the heck is a polymer? David E. Sloane, MD

  8. What is DNA? The Double Helix (Nature, 1953) 23 Chromosomes 3.08 x 109 base pairs David E. Sloane, MD

  9. How does DNA copy itself? • DNA replication • (50 nucleotides per second) • Exercise 1 • What are mutations? • What are variations? • thedogwasbigandfatandsadandbadbutthecatwasfunandherearwasred • thedogwasbigandfatandsmadandbadbutthecatwasfunandherearwasred • thedogwasbigandfatandmadandbadbutthecatwasfunandherearwasred • thedogwasbigandfatandadandbadbutthecatwasfunandherearwasred David E. Sloane, MD

  10. How does the information in DNA get expressed? • The flow of information: the central dogma of biology • DNA → RNA → Protein • DNA → RNA = “transcription” • RNA → Protein = “translation” • But in HIV: RNA → DNA → RNA → Protein • RNA is ribonucleic acid, moves from nucleus (where DNA is sequestered) to cytoplasm • Proteins are un-branched polymers of amino acids David E. Sloane, MD

  11. Transcription Exercise 2 David E. Sloane, MD

  12. Twenty Amino Acids David E. Sloane, MD

  13. Encoding Amino Acids David E. Sloane, MD

  14. The RNA siblings: m, t, and r David E. Sloane, MD

  15. Translation Exercise 3 David E. Sloane, MD

  16. Exons, Introns, Alternative Splicing Figures from Korf and Irons 2013 David E. Sloane, MD

  17. What are gene regulatory networks? • In a word “epigenetics” • some proteins affect DNA replication, transcription, and translation • So the “end products” of the linear sequence DNA → RNA → Protein feed back on the system. So it’s not really linear at all. Nature vs. Nurture David E. Sloane, MD

  18. A (super) simple gene regulatory network David E. Sloane, MD

  19. Epigenetics • What parts of the genome are expressed, • How much a given gene is expressed, and • In what context the gene is expressed…. are influenced by the environment! Metaphorically speaking, the restaurant customers influence the reading of the cookbook. But how do the genome and the environment interact to result in a given phenotype? David E. Sloane, MD

  20. Mechanisms of Epigenetics • DNA Methylation Figure from Korf and Irons 2013 David E. Sloane, MD

  21. Mechanisms of Epigenetics • microRNAs (miRNAs) Figure from Korf and Irons 2013 David E. Sloane, MD

  22. What are some DNA tests germane to mind-brain research? • rtPCR • The Human Genome Project • Gene Chip Analysis David E. Sloane, MD

  23. Single Nucleotide Polymorphism (SNP) Detection David E. Sloane, MD

  24. MicroArray David E. Sloane, MD

  25. Let’s have a (nice) fight… • One of western medicine’s big problems: • one dose treats all • But let’s extend this (reducto ad absurdum) David E. Sloane, MD

  26. Homeopathy David E. Sloane, MD

  27. Homeopathy David E. Sloane, MD

  28. Thanks! • des770@mail.harvard.edu David E. Sloane, MD

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