BIOL + BMSC 241

TOPICS IN MOLECULAR GENETICS

AND
MOLECULAR BIOLOGY

Dr Geoffrey K. Chambers
2009
Introducing our mascot ……..
 1. THE BASICS

A quick overview of what is known and

what is to be known
 LEARNING OBJECTIVES

1. Build upon basic knowledge of DNA etc.

2. Develop understanding of biological information:

• Storage, content and expression
• Manipulation and analysis
• Case study examples

3. See some applications – transgenics etc.

 DELIVERY STYLE

• A reading list has been supplied

• Lecture notes will be posted on BlackBoard

• Class members attend lectures:
– Add explanations to notes; VERY IMPORTANT

• Class members must read iGenetics 3rd Ed.:

– Extend knowledge and understanding
 A SHORT HISTORY (I)

1900s abstract gene concept and mapping

1940/50s DNA is the genetic material
1950/60s DNA structure established
1960s physical gene concept
1960s genetic code worked out

‘Molecular Biology’ born in Leeds, UK in 1961

 A SHORT HISTORY (II)
1970s DNA manipulation enzymes
DNA cloning and sequencing methods
1980s gene isolation and analysis methods
first GMOs
1990s application to many fields
2000s whole genome projects
functional genomics
bioinformatics
… so just 40 years later we have the full Human Genome sequence
STARTING REQUIREMENTS

1. The language of genetics

2. DNA and RNA structure and properties
3. Fundamental cellular processes:
• Mutation, repair and synthesis of NA
• Transcription and translation

4. Basic concepts of cloning etc.

5. Understanding of ‘biological information’ idea

 DNA IS A CHEMICAL
• Easy to isolate from cells; phenol/CHCl3 etc.
• Easy to assay:
– A260 measurement
– Agarose gel electrophoresis

• Easy to read nucleotide sequences in DNA

• Easy to copy SHORT segments of genes (PCR)
• Easy to make from scratch:
– Commercial suppliers use solid phase
phosphoramidate synthesis
 BIOLOGICAL INFORMATION

Consider the ‘computer analogy’

• The genome ≡ hard drive contents

• 4 base (A,C,G,T) code vs. binary (1,0) code
Structural Genes ≡ files Cellular machines
Regulatory Genes ≡ software RNA and/or Proteins
e.g. ribosome ‘hardware’

• Communication via molecules; e.g. cytokines

• Self-regulated vs. owner-operated
ABSTRACT GENE CONCEPT
• Particulate entities

• Mutational property:
– Alternate alleles
– Dominant/recessive character (gain/loss of function)

• Fixed ordered locations

• Re-assortment property; Mendelian character

• Recombination property; valuable for mapping

PHYSICAL GENE CONCEPT

• Consecutive DNA (RNA) nucleotide sequences

• Encode one (or more) product

• Genotype  phenotype (more or less)

THE OLD VIEW OF GENES

The ‘bead on a string’ model

One gene makes one protein

OUR NEW VIEW OF GENES

Enhancer Promoter E1 E2 E3A E3B AAA Stop

ATG

ATG – translation start site

E1 – E3 – exons

AAA – polyadenylation site

Transcription unit starts from the right arrow and proceeds to Stop
The mature poly A+ mRNA contains either E3A or E3B sequences
due to ‘alternate splicing’
THE CENTRAL DOGMA

This set of relationships is commonly known as

the ‘Central Dogma of Molecular Biology’