BL414 Genetics Spring 2006
Lecture 1 Outline
January 18, 2006
Introduction to genetics:
What are genes?
Genes are the elements of heredity transmitted from parents to offspring.
The questions that follow from the understanding of genes existing in organisms are:
What exactly are they made of?
How do they affect an organism?
How do genes actually work?
What exactly are genes made of?
1.1 DNA the Genetic Material
Historical progress and context of the search for the answers to these questions:
 1869 Miescher found what was later to be known as DNA in the nucleus
 1880’s chromosomes were observed in cells undergoing mitosis (not seen in nucleus, only when nucleus disappears during cell division)
 1900’s became generally thought that chromosomes carry “genes” but still not known exactly how; Emil Fischer showed that proteins consist of long strings of amino acids – perhaps thousands of different amino acids were thought to exist in proteins. (Later it was found that there are 20 amino acids. Protein folding accounts for some of the incredibly diverse forms and functions of proteins).
 1920’s Robert Fuelgen observed that DNA is exclusively in the chromosomes. DNA was known to consist of 4 types of nucleotides, and therefore was thought to not be complex enough to be the substance of genes. It was thought that proteins were most likely to be the substance of genes, with DNA perhaps in a scaffolding role.
Key experiments finally led to the realization that genes were comprised exclusively of DNA.
 1920’s Griffith

o injected live non-virulent and killed virulent bacteria into mice, and the mice died o showed that genetic material can be transferred from one
 bacterial cell to another
1940’s Avery, MacLeod, and McCarty at Rockefeller University o isolated DNA, transformed bacteria o showed that transforming substance was not susceptible to protease, but it is susceptible to DNases  therefore the transforming substance, i.e. the genetic material, was DNA!
 1952 Hershey and Chase o showed that only the DNA enters bacterial cell from phage virus; protein coat stays outside
1.2 DNA Structure
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The Double Helix, 1953 Watson and Crick o DNA consists of two strands of phosphodiester linked nucleotides with four different base constituents: adenine, guanine, cytosine and thymine. The adenine nucleotides are always arranged in a base pair with thymine and the guanosine is always paired with cytosine. Therefore, the two strands are complementary to each other.
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DNA Replication o In order for DNA to replicate, the two strands of the double helix are unfolded and a new complementary strand is created for each half. The resulting two daughter double helices are identical to the original parent double helix.
So, how do genes affect an organism?
1.4 Genes and Proteins:

1908 Archibald Garrod through his studies of “black urine disease”
(alkaptonuria) found that certain diseases can be inherited according to the same rules described by Mendel – that is, genes can cause a defect in some normal biological function, leading to disease
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These hereditary diseases were dubbed “inborn errors of metabolism.”

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This idea was expanded to the understanding that a given gene is responsible for a single enzyme or a single protein
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At the time of Garrod, it was not understood how genes directed the activity of a protein – it might have been assumed that genes were the proteins – some how they replicated and were activated
Then, how do genes actually work?
1.5 Gene Expression: The central dogma.
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The discovery of the double helix was followed by a chase after the
“code” – the understanding of how the nucleotide sequence on a strand of DNA directed the creation of specific proteins.
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A new player was realized to be of great importance, messenger
RNA (mRNA), which carries the genetic sequence of a gene that has been transcribed from the DNA, and is then used as a template for translation into protein by ribosomes.
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RNA also has other functional roles in the cell, for example there is
ribosomal RNA within every ribosome, which operates in the catalytic center of the ribosome and is also involved in many interactions with the many ribosomal proteins that make up this small organelle. Transfer RNA (tRNA) is very important to the central dogma and to translation – each tRNA is attached to a particular amino acid – tRNA is the linker molecule between the genetic code and the amino acid sequence of proteins.
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The central dogma of molecular genetics is that DNA is transcribed into RNA, which is in turn translated into protein.
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The genetic code consists of three nucleotides that encode a particular amino acid. The three nucleotide group is called a codon.
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Transcription is the process by which and RNA strand is created from a DNA template
– the RNA sequence is complementary to one of the DNA strands, and therefore it carries the code of the gene encoded on the DNA. The RNA molecule that is created is called a transcript. This process is carried out by RNA polymerase.
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Translation is the process of creating a protein, or polypeptide chain, that has the amino acid sequence encoded on the mRNA transcript. This process is carried out by ribosomes and tRNA’s which carry amino acids.

1.6 Mutation refers to a heritable change in a gene – physically it is created by a change in the sequence of a gene, which could be the change of a single nucleotide, or something more extensive such as an insertion or deletion of multiple bases. The term mutant refers to the result of a particular mutation, and could refer to the mutant gene, a mutant protein, or a mutant organism.
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The mutant gene can affect the proper functioning of a gene in several ways – the protein could be not expressed at all (loss of function), the protein could be expressed but not function properly
(loss of function), the protein could be expressed but in a form that actively disables or disrupt other biological functions in a cell (gain of function), or the protein could be overexpressed so there is too much of that protein and it does not fulfill its role properly or it disrupts other biological functions in the cell (gain of function).
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Protein folding has an important role in the proper functioning of proteins, because function depends upon form. Your book uses the
PAH gene as an example. The gene encodes phenylalanine hydroxylase (PAH) which converts phenylalanine to tyrosine.
1.7 Genes and environment:
 The expression of genes and how they function is also affected by the environment and experiences of the particular organism. e.g. patients with
PKU disease can live healthy lives if they restrict phenylalanine (no meat, poultry, fish, eggs, milk or milk products, etc.) in their diet. If phenylalanine is not restricted a PKU patient can develop mental retardation.
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Pleiotropy: the condition in which a single mutant gene affects two or more distinct and semmingly unrelated traits. Some genes have pleiotropic effects, whereby they affect multiple yet seemingly unrelated traits through secondary or downstream effects. For example, some children with PKU also have reduced body pigment because PAH blocks the production of tyrosine, which is a precursor form of melanin.
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Many traits are affected by multiple genes. For example, genes involved in the maintenance of the blood-brain barrier are important to determining the severity of the PKU disease.
Genome: The total set of genes contained in a cell or virus; in eukaryotes, commonly used to refer to all genes present in one complete haploid set of chromosomes.

Proteome: The total set of proteins present in a cell or organism. (differs from genome in that is depends on which genes are expressed in particular cells, tissues, at different times of development, or in response to certain environmental factors.
Chapter 2: DNA Structure and DNA Manipulation
2.2 The molecular structure of DNA more detail on the biochemical nature of DNA strands and DNA folding
2.3 Separation and Identification of Genomic DNA Fragments
Hybridization: annealing of a DNA fragment of known sequence, to a larger amount of DNA
Polymerase chain reaction: amplification of a small amount of DNA using the cycles of annealing and replication of DNA, depends upon small fragments of
DNA called primers which select the sequence boundaries of DNA to be amplified
Restriction enzymes: recognize and cleave DNA at short characteristic sequences, also called restriction endonucleases
Restriction site: the particular site on DNA that is recognized by a restriction enzyme
Gel electrophoresis: process by which DNA fragments can be separated according to size, depends on the movement of the charged DNA molecules through a gel through which an electric current is applied. DNA is visualized as bands in the gel.
Denaturation: the separation of two strands in a DNA double helix
Renaturation: the coming together of two complementary strands of DNA – also called hybridization