Classical Genetics

The Genome Contains The Entirety Of An Organism's Hereditary Information. If the DNA from a single (diploid) human cell were connected end-to-end and straightened, it would have a length of ~2 m and a width of ~2.4 nanometers Challenge In humans the entire stretch of DNA polymer is made of ~ 3·10 9 monomer units

IF YOU HAD A REALLY LONG STRING HOW WOULD YOU ORGANIZE IT? Question:

WHAT IF FROM TIME TO TIME YOU HAD TO ACCESS PART OF THE STRING? Another Question

The DNA is compacted into Chromosomes. highly condensed nuclear structures histone proteins

The DNA is compacted into Chromosomes. highly condensed nuclear structures histone proteins

Humans Have 23 Pairs of Chromosomes in (Diploid) Cells

Gene Gene is a stretch of DNA that contains the instructions for making a protein

With Better Understanding of Genomics, The Definition Of A Gene Has Changed DNA segment that encodes for a protein when and where it is made new definition of a Gene

This small subset of atoms provides an extensive molecular diversity 6 Atomic Constituents: C, H, N, O, P, S Build 99.6% Of All Living Matter

DNA, RNA: 4 nucleic bases Proteins: 20 amino acids 3 essential biomolecules for existence and continuation of life: variable units All life is based on complex structures (DNA, RNA, Proteins) which are made of these 6 elements

Adenine Guanine Thymine Cytosine 4 Nucleic Bases: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C) Genetic code for DNA 2 strands of backbone locked by base pairs double helix

Adenine Guanine Thymine Cytosine 4 Nucleic Bases: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C) Genetic code for DNA Pairing A-T G-C 2 strands of backbone locked by base pairs double helix

Hydrogen Bonding Helps Stabilize DNA H-bonding  attractive force between one electronegative atom (O,F, N) and a hydrogen covalently bonded to another electronegative atom.

Hydrogen Bonding Helps Stabilize DNA example: Kevlar derives part of its high strength from inter-molecular hydrogen bonds on neighboring polymer chains and aromatic (ring) stacking interactions between stacked strands

Nucleotide Pairing Is A Result of Hydrogen Bonding

The Structure of DNA Repetitive Structure Backbone Uniform Helix 0.34 nm

chemical variability nucleic bases in arbitrary sequence base -sequence encodes the meaning Notice that the widths of the pairs A-T and G-C are equal The Structure of DNA

Base compositions experimentally determined for a variety of organisms SpeciesA:TG:CA:G H. sapiens Salmon Wheat Yeast E. coli S. marcescens

Watson, Crick… Watson and Crick and Franklin

The structure of DNA: Notice that the widths of the pairs A-T and G-C are equal

The structure of DNA: Why is this significant ? chemical variability nucleic bases in arbitrary sequence Notice that the widths of the pairs A-T and G-C are equal base -sequence encodes the meaning Physically Repetitive, Chemically Variable repetitive structure repetitive structure backbone backbone uniform helix uniform helix

The structure of DNA: Physically Repetitive, Chemically Variable  Readability requires some sort of regular structure that can be algorithmically sifted through (semi-conservative replication)  Chemically variability in sequence provides a meaning and a genetic diversity Notice that the widths of the pairs A-T and G-C are equal chemical variability nucleic bases in arbitrary sequence base -sequence encodes the meaning repetitive structure repetitive structure backbone backbone uniform helix uniform helix

DNA Replication Is Semi-Conservative Provides opportunity for introduction and preservation of Novelty

semi-conservative replication of DNA

Cytosine 4 Nucleic Bases: Adenine (A), Uracil (U), Guanine (G), and Cytosine (C) Uracil Adenine Guanine Genetic code for RNA 1 strands of backbone with base pairs single helix Triplet of RNA bases (codon) translates into a particular amino acids

The Genetic Code Consists of Triplets of Bases Called Codons

The Order of Amino Acids Helps Determine the Shape of the Protein

Overview of What We’ve Discussed This AM: The structure of DNA: Shape governs the Function (Meaning)

The Hershey-Chase Experiments: What is the Hereditary Material Proteins or DNA? Use a Virus Let it infect a bacteria Radioactively label DNA & Proteins: 32 P-labeled DNA 35 S-labeled Protein

The Hershey-Chase Experiments: DNA is the Hereditary Material 32 P-labeled DNA 35 S-labeled Protein 2/3 within bacterium 1/4 within bacterium

1) DNA encodes RNA 2) RNA encodes Proteins 3) Proteins encode shape/function  Genetic information (the MEANING) is encoded in the SEQUENCE of basis along the DNA strand;  DNA is not a direct template for protein synthesis; The Central Dogma of Molecular Biology: DNA  RNA  Protein

The History of Classical Genetics NATURE|Vol 441|25 May 2006

Classical Genetics NEW CORE CURRICULUM: FOUNDATIONS OF THE SCIENTIFIC PROCESS

1) DNA encodes RNA 2) RNA encodes Proteins 3) Proteins encode shape/function Genetic information (the MEANING) is encoded in the SEQUENCE of basis along the DNA strand; DNA is not a direct template for protein synthesis; The Central Dogma of Molecular Biology: DNA  RNA  Protein

In the beginning… NATURE|Vol 441|25 May 2006 Mendel Johansen Morgan

1941. Single Genes… Single Enzymes Johansen Beadle Tatum

1944. Genes are Made of DNA Avery MacLeodMcCarty

1953. Structure of DNA WatsonCrickWilkinsFranklin

1977. Introns RobertsSharp

1993. The first μRNA identified in C. elegans

Establishing Basic Terminology and Definitions: Gene = is a stretch of DNA that contains the instructions for making a protein; Allele = alternative forms of genes for a certain characteristics (ex. alleles for flower color or earlobe shape); Homozygous (EE, ee) & Heteorzygous (Ee); Genotype = genetic makeup of an organism; Phenotype = observed characteristics of organism; The phenotype is produced by the interaction of genes and the environment.

It has been long known that offspring resemble parents. Animals and plants selectively bred for many centuries. Gregor Mendel was the first to explain the principles of heredity in the mid-nineteenth century. He investigated heredity in pea plants Garden pea grow easily, produce large numbers of seeds quickly, and self-fertilize. Pea Plants have distinctive characters: Purple OR White flowers

Mendel isolated true-breeding strains Traits were selected because they had two distinct phenotypes Scientific Process of discovery….establishing Classical Genetics

Mendel crossbred plants with different alleles Gamete is a cell that is involved in sexual reproduction. A male and female gamete unite to produce a zygote that will develop into offspring.

Interpretation of Mendel’s Results  Laws of Heredity: Law of dominance: When an organism has 2 alleles for a given trait, the allele that is expressed (overshadows the expression of the other allele) is the dominant allele. The overshadowed allele is called recessive allele. notation convention: Y - dominant allele (ex. purple) y - recessive allele (ex. white) YY - homozygous dominant Yy - heterozygous yy - homozygous recessive

Deleterious recessive alleles persist in the population because heterozygous individuals carry the allele without developing the phenotype, and are not at a selective disadvantage. If both parents are homozygous for the recessive trait, all their progeny will usually also have the trait. Recessive traits are usually the result of a mutation causing loss or modification of gene product. ex. Albinism: characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin You could construct a family tree of either your family or friend’s family by using character for ear lobe type (recessive vs. dominant) non-attached is dominant

Co-Dominance Both alleles, when present, will contribute equally to the phenotype. Blood typing in humans- the ABO system; Rh factor incompatibility (erythrobalstosis feotalis). Terms: antigen, antibody, agglutination, Rh factor

Co-Dominance

Incomplete Dominance

Interpretation of Mendel’s Results  Laws of Heredity: Law of dominance: When an organism has 2 alleles for a given trait, the allele that is expressed (overshadows the expression of the other allele) is the dominant allele. The overshadowed allele is called recessive allele. Law of segregation: Parental alleles of a gene separate in process called meiosis into gametes (reproductive cells). In the process of gametes formation, the alleles that control a trait separate form one another retaining their individuality. Law of independent assortment: If two different genes are found on separate chromosomes, where the one allele goes is not influenced by where the other goes.

Law of Segregation

Law of Independent Assortment

parental alleles of a gene separate in process called meiosis into gametes semi-conservative replication of DNA

Next time…more about current efforts in Genetics