Gene and Genome

Prof. DR. dr. Hadyanto Lim, M.Kes, SpFK, FESC, FIBA, FAHA
Department of Pharmacology and Molecular Sciences, Faculty of Medicine, UMI- Medan Molecular Biology Research, Postgraduate School, USU

Molecular Biology
Day/Date/Time *
Wed /19/9/12 Fri /21/9/12 Wed /26/10/12 Fri /28/10/12

Topic
Gene &Genome Expression of Genetic Information : From Transcription to Translation Control of Gene Expression DNA Replication and Repair

* Class A (9.00-10.00) Class B (800-900) FK UMI * 26-28 September 2012 ; Class A (11.00-12.00) Class B ( 10.00-11.00)

Nobel Laureates Medicine Watson Crick in Double Helix (Molecular Biology in 1962)

Francis Crick, Maurice Wilkins, James Watson

Discoveries on the Nature of the Gene

Discoveries on the Nature of the Gene

Discovery of discrete unit of inheritance Discovery of chromosome Discovery of homologous chromosome Discovery of crossing over Discovery that genes could be mapped in order along length of chromosomes Discovery of DNA as genetic material Discovery of DNA structure Human Genome Project.

Gene as a unit of inheritance

1860s Gregor Mendel crossbred plants through several generations and counted the number of individuals having various characteristics : 1. The characteristics of the plants were governed by distinct factors (or units) of inheritance, later termed genes. An individual plant possessed two copies of a gene that controlled the development of each trait, one derived from each parent. Alternate forms of a gene are called alleles.

Gene as a unit of inheritance

2. One of the alleles that governed each trait in a plant was inherited from female parent, and the other allele was inherited from the male parent.

3. The pair of alleles that governed a trait remained together throughout the life of an individual plant, but they become separated (or segregated) from one another during the formation of the gametes. This finding formed the basis of Mendels law of segregation.

Gene as a unit of inheritance

4. A particular gamete, could receive a paternal gene governing seed color and a maternal gene governing seed shape. This finding formed the basis of Mendels law of independent assortment. Mendels experiments were published in the Brunn societys journal in 1866, where they generated no interest whatsoever until 1900, 16 years after his death.

Discoveries on the Nature of the Gene

Discovery of discrete unit of inheritance Discovery of chromosome Discovery of homologous chromosome Discovery of crossing over Discovery that genes could be mapped in order along length of chromosomes Discovery of DNA as genetic material Discovery of DNA structure Human Genome Project.

Chromosome
1880s Walther Flemming discovered chromosome (colored bodies), visible threads in the nucleus of a eucaryotic cell that become visible by light microscope as the cell begins to divide.

Chromosome
1903, Walter Sutton, a graduate student at Columbia University, pointed that the chromosome as the physical carriers of Mendels genetic factors; the presence in each cell of pairs of chromosomes, or homologous chromosomes (pairs of inheritable factors) uncovered by Mendel (11 pairs chromosomes and 1 sex-determining X chromosome). And genes on the same chromosome should act as if they are linked to one another; linkage group, as observed by Mendels alleles (genes should be passed from parent to offspring in packages, Mendels law of independent assortment).

Chromosome
Chromosome consists of both deoxyribonucleic acid (DNA) and protein. But as the 1950s began, both how proteins could be specified by instructions in the DNA and how this information might be copied for transmission from cell to cell seemed completely mysterious.

Discoveries on the Nature of the Gene

Discovery of discrete unit of inheritance Discovery of chromosome Discovery of homologous chromosome Discovery of crossing over Discovery that genes could be mapped in order along length of chromosomes Discovery of DNA as genetic material Discovery of DNA structure Human Genome Project.

Drosophila Melanogaster (Fruit Fly)

Thomas Hunt Morgan, Columbia University (1915)
Wild Type Mutant

New Era in Genetic Research

Genetic Analysis Of Drosophila

The generation time (from egg to sexually mature adult) of about 10 days and can produce up to 1000 eggs in a lifetime. Easy to house and breed. Very inexpensive to maintain. Wild type strain (normal) the only fly available from the beginning. The altered trait (mutant), occurs within a gene passed from generation to generation.

Genetic Analysis Of Drosophila

Crossing over (or genetic recombination) could account for the appearance of offspring (recombinants) having unexpected combinations of genetic traits (Morgan).

Jansens had proposed that the interaction between maternal and paternal chromosomes resulted in the breakage and exchange of pieces.

Crossing over in Paternal and Maternal Chromosomes

Sites of crossing over

Mutagenesis
Morgan experiment - depends on spontaneous appearance of altered genes. HJ Muller, Indiana University flies subjected to a sublethal dose of X-rays displayed more than 100 times the spontaneous mutation rate exhibited by nonirradiated controls.

Today, mutagenesis in Drosophila are most often generated by adding a chemical mutagen (ethyl methane sulfonate) to the animalss feed.

Discoveries on the Nature of the Gene

Discovery of discrete unit of inheritance Discovery of chromosome Discovery of homologous chromosome Discovery of crossing over Discovery that genes could be mapped in order along length of chromosomes Discovery of DNA as genetic material Discovery of DNA structure Human Genome Project.

DNA as genetic material

Base Composition of DNA

1950 Erwin Chargaff, Columbia University, delivered the final blow to the tetranucleotide theory and provided vital information about DNA structure.

Tetranucleotide theory : the number of purines (Adenine-Guanine) ratio always equaled the number of pyrimidines (Thymine-Cytosine) in a given sample of DNA. More specifically, the number of adenines always equaled the number of thymines, and the number of guanines always equaled the number of cytosines

Base Composition of DNA

Chargaff discovered the following rules of DNA base composition : A = T, G = C, A + T G + C

Discoveries on the Nature of the Gene

Discovery of discrete unit of inheritance Discovery of chromosome Discovery of homologous chromosome Discovery of crossing over Discovery that genes could be mapped in order along length of chromosomes Discovery of DNA as genetic material Discovery of DNA structure Human Genome Project.

Discovery of DNA Structure

February 28, 1953 Crick and Watson, discovered the structure of DNA at Cambridge, England. Crick announced that we had found the secret of life. The DNA structure is a double helix April 14, 2003, the National Human Genome Reserach Institute announced the successful completion of the Human Genome Project

Watson and Crick

Time/CBS News People of the Century p. 301

DNA and its building blocks

DNA is made from simple subunits, called nucleotides, each consisting of a sugar-phosphate molecule with a nitrogen-containing side group, or base, attached it. The bases are of four types (adenine, guanine, cytosine, and thymine), corresponding to four distinct nucleotides, labelled, A,G, C, and T. A single strand of DNA consists of nucleotides joined together by sugar-phosphate linkages.

DNA and its building blocks

Through templated polymerization, the sequence of nucleotides in an existing DNA strand controls the sequence in which nucleotides are joined together in a new DNA strand; T in one strand pairs with A in the other, and G pairs with C. A normal DNA molecule consists of two such complementary strands. The nucleotides within each strand are linked by strong (covalent) chemical bonds; the complementary nucleotides on opposite strands are held together more weakly, by hydrogen bonds.

The DNA Double Helix

The two strands twists around each other to form a double helix a robust structure that can accommodate any sequence of nucleotides without altering its basic structure.

DNA and its building blocks

The DNA Double Helix

Double Helix

Discoveries on the Nature of the Gene

Discovery of discrete unit of inheritance Discovery of chromosome Discovery of homologous chromosome Discovery of crossing over Discovery that genes could be mapped in order along length of chromosomes Discovery of DNA as genetic material Discovery of DNA structure Human Genome Project

Genome
The term genome is the complete set of information in an organisms DNA. Genome carries the information for all the proteins and RNA molecules that the organism will ever synthesize. The term genome is also used to describe the DNA that carries this information. The human genome-approximately 3.2 x 109 nucleotides is distributed over 24 different chromosomes.

The Structure of DNA Provides a Mechanism for Heredity

The organization of genes on a human chromosome

Dark brown = known genes; red, predicted genes

Exon (red), the coding sequence, codes for a portion of protein Intron, (gray) , intervening (noncoding) sequence

Venter's own DNA sequence (September 4, 2007)

The first complete (six-billion-letter) genome of an individual human Founder The Institute of Genomic Research

A New Reprogramming Technology in Stem Cell

References
Profesor Hadyanto Lim, Revolusi Sel Punca Kedokteran Kardiovaskuler. vol 1, PT Sofmedia, October 2010. Profesor Hadyanto Lim, Revolusi Stem Cell Therapy Penyakit Kardiovaskuler, vol 2, PT Sofmedia, 2011 Alberts B. ed. Molecular Biology of the Cell. 5th ed. Garland Science, 2008.