Molecular BiologyFifth Edition

Chapter 1

A Brief History

Lecture PowerPoint to accompany

Robert F. Weaver

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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A Brief History

• 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 melding 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

• The chemical composition of genes was not known until 1944– Gene - genetic units– Phenotype - observable characteristics

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Mendel’s Laws of Inheritance

• 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 Laws of Inheritance• Homoozygotes have two copies of the same allele• Heterozygotes have one copy of each allele• Parents in 1st mating are homozygotes, having 2

copies of one allele• Sex cells, or gametes, are haploid, containing only

1 copy of each gene• Heterozygotes produce gametes having either

allele • Homozygotes produce gametes having only one

allele

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Summary

• Genes can exist in several different forms or alleles

• One allele can be dominant over the other, so

heterozygotes having two different alleles of one

gene will generally exhibit the characteristic

dictated by the dominant allele

• The recessive allele is not lost; it can still exert its

influence when paired with another recessive allele

in a homozygote

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The Chromosome Theory of Inheritance

• Chromosomes are discrete physical entities that carry genes

• Thomas Hunt Morgan used the fruit fly, Drosophila melanogaster, to study genetics

• Autosomes occur in pairs in a given individual (not the X or the Y chromosome)

• Sex chromosomes are identified as X and Y– Females have two X chromosomes– Males have one X and one Y chromosome

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Location of Genes on a Chromosome

• Every gene has its place, or 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

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Genetic Recombination and Mapping

• In early experiments genes on separate chromosomes behaved independently

• Genes on the same chromosome behaved as if they were linked

• This genetic linkage is not absolute

• Offspring show new combinations of alleles not seen in the parents when recombination occurs

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Recombination

• During meiosis, gamete formation, crossing over can occur resulting in the exchange of genes between the two homologous chromosomes

• The result of the crossing-over event produces a new combination of alleles

• This process is called recombination

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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

• If two loci recombine with a frequency of 1%, they are said to be separated by a map distance of one centimorgan (named for Morgan)

• This mapping observation applies both to prokaryotes and to eukaryotes

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Physical Evidence for Recombination

• Microscopic examination of the maize chromosome provided direct physical observation of recombination using easily identifiable features of one chromosome

• Similar observations were made in Drosophila

• Recombination was detected both physically and genetically in both animals and plants

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Summary• The chromosome theory of inheritance holds that

genes are arranged in linear fashion on chromosomes

• Certain traits tend to be inherited together when the genes for those traits are on the same chromosome

• Recombination between two homologous chromosomes during meiosis can scramble the parental alleles to yield nonparental combinations

• The farther apart two genes are on a chromosome the more likely it is that recombination will occur

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1.2 Molecular Genetics

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

phosphate groups

• Composition of Genes: DNA? RNA? Protein? In 1944, Avery and his colleagues demonstrated that genes are composed of DNA

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The Relationship between Genes and Proteins

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

• This lead to the proposal that one gene is responsible for making one enzyme

• Proposal not quite correct for 3 reasons:1. One enzyme may be composed of several

polypeptides, each gene codes for only one polypeptide

2. Many genes code for non-enzyme proteins3. End products of some genes are not

polypeptides (i.e. tRNA, rRNA)

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Activities of Genes

Genes perform three major roles

• Replicated faithfully

• Direct the production of RNAs and proteins

• Accumulate mutations thereby allowing for evolution

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Replication• Franklin and Wilkins produced x-ray

diffraction data on DNA, Watson and Crick proposed that DNA is double helix– Two DNA strands wound around each other– Strands are complementary – if you know the

sequence of one strand, you automatically know the sequence of the other strand

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

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Genes Direct the Production of Polypeptides

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

• Two steps are required– 1. Transcription: DNA is transcribed into RNA– 2. Translation: the mRNA is read or translated

to assemble a protein – Codon: a sequence of 3 nucleic acid bases

that code for one amino acid within the mRNA

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Genes Accumulate Mutations

Genes change in several ways• Change one base to another• Deletions of one base up to a large

segment• Insertions of one base up to a large

segment• The more drastic the change, the more

likely it is that the gene or genes involved will be totally inactivated

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Summary• All cellular genes are made of DNA

arranged in a double helix• This structure explains how genes replicate,

carry information and collect mutations• The sequence of nucleotides in a gene is a

genetic code that carries the information for making an RNA

• A change in the sequence of bases constitutes and mutation, which can change the sequence of amino acids in the genes polypeptide product

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1.3 The Three Domains of Life

Current research theories support the division of living organisms into three domains1. Bacteria2. Eukaryota3. Archaea

• Like bacteria as they are organisms without nuclei

• More similar to eukaryotes in the context of their molecular biology

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ArchaeaArchaea 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