A Brief History

Chapter 1

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What is Molecular Biology?

• The attempt to understand biological phenomena in molecular terms

• The study of gene structure and function at the molecular level

• Molecular Biology is a combination of aspects of Genetics and Biochemistry

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1.1 Transmission Genetics

• Transmission genetics deals with the transmission of traits from parental organisms to their offspring (work of Mendel)

• Chemical composition of genes not known until 1944– Gene– Phenotype

1.1 Transmission Genetics

• Blending of traits of parents – inheritance – offspring

• Mendel’s research – inheritance is particulate - Important generalizations – phenotype and

genotype

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Mendel’s Laws of Inheritance (1865)

• A gene can exist in different forms called alleles

• One allele can be dominant over the other, recessive allele

• The first filial generation (F1) contains offspring of the original parents

• If each parent carries two copies of a gene, the parents are diploid for that gene

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Mendel’s Gene Transmission

• Parents in 1st mating are homozygotes - 2 copies of one allele

• Heterozygotes have one copy of each allele

• Sex cells or gametes are haploid containing only 1 copy of each gene

The Chromosome Theory of Inheritance

• Mendel’s work criticized

• Understanding of particulate nature of genes and nature of chromosomes

• Chromosomes are discrete physical entities that carry the genes

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Proof – The Chromosome Theory of Inheritance

• Thomas Hunt Morgan used the fruit fly - Drosophila melanogaster

• Concept - Autosomes occur in pairs in a given individual

• Sex chromosomes are identified as X and Y– Female has two X chromosomes– Male has one X and one Y chromosome

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What is Locus?

• Every gene is present on locus on a chromosome

• Genotype is the combination of alleles found in an organism

• Phenotype is the visible expression of the genotype– Wild-type phenotype is the most common or

generally accepted standard– Mutant alleles are usually recessive

Genetic Recombination and Mapping

• During meiosis - gamete formation - crossing over occurs

• The result of the crossing-over event – Recombination

• Produces a new combination of alleles

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Genetic Mapping

• Morgan proposed that the farther apart two genes are on a chromosome - the more likely they are to recombine

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1.2 Molecular Genetics

• The Discovery of DNA: The general structure of nucleic acids were found by the end of the 19th century– Long polymers or chains of nucleotides– Nucleotides are linked by sugars through

phosphate groups• Composition of Genes: In 1944, Avery and his

colleagues demonstrated that genes are composed of nucleic acids

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The Relationship between Genes and Proteins

• Experiments have shown that a defective gene gives a defective or absent enzyme (Garrod)

• Led to the proposal that one gene is responsible for making one enzyme (Beadle & Tatum)

• Proposal not quite correct1. Enzyme may have several polypeptides, each

gene codes for only one polypeptide2. Many genes code for non-enzyme proteins3. End products of some genes are not polypeptides

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What are the activities of genes?

Genes perform three major roles• Replicated faithfully

• Direct the production of RNAs and proteins

• Accumulate mutations thereby allowing evolution

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How does DNA replicate?

• Watson and Crick proposed that DNA is double helix– Two DNA strands wound around each other– Strands are complementary

• Semiconservative replication keeps one strand of the parental double helix conserved in each of the daughter double helices

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How do genes direct the production of polypeptides?

• Gene expression is the process by which a gene product is made

• Two steps are required– Transcription: copy of DNA is transcribed into RNA

– Translation: the RNA copy is read or translated to assemble a protein

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How do genes accumulate mutations?

Genes change in several ways• Change one base to another

• Deletions or Insertions of one base or large segment

• More drastic the change, the more the inactivation of gene

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1.3 What are the three domains of life?

Current research theories support the division of living organisms into three domains1. Bacteria/Prokaryotes 2. Eukaryota 3. Archaea

Archaea live in the most inhospitable regions of the earth• Thermophiles tolerate extremely high temperatures• Halophiles tolerate very high salt concentrations• Methanogens produce methane as a by-product of

metabolism

History of the gene: 1869-1970:• 1869 - The chemical material DNA is discovered in cells but its real functions

are not known. • 1909 - The term "gene" is first used and the chemical composition of DNA is

discovered. • 1920 - Chromosomes are proposed as the mechanism by which inherited

characteristics are passed on. • 1944 - DNA is first connected to the inheritance of traits. • 1951 - The first sharp X-ray diffraction photographs of DNA are obtained. • 1953 - Crick and Watson describe the structure of DNA. • 1956 - DNA is made artificially. • 1966 - DNA is found to be present not only in chromosomes but also in the

mitochondria. • 1969 - The first single gene is isolated. • 1970 - The first artificial gene is made.

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