Genetics Lecture Notes 7 03 2006 Lectures 1 2 7 03 Fall 2006 Lectures 1 2 1 of 9 Lecture 1 We will begin this course with the question What is a gene This question will take us four lectures to answer because there are actually several different definitions that are appropriate in different contexts We will start with a physical definition of the gene Conceptually this is the simplest and it will give me an excuse to briefly review some of the molecular biology that you probably already know Genes are made of DNA For this course we will mostly think of DNA as an information molecule rather than a chemical substance In 1953 Watson and Crick deduced that the structure of DNA was a double helix It was not the helical structure per se but the discovery of complementary base pairing that revealed how information could be encoded in a molecule and how this information could be exactly duplicated each cell division Replication 7 03 Fall 2006 Lectures 1 2 2 of 9 In order to extract information from the DNA the cell again uses the complementary base pairing to make a copy of the information copied onto an RNA molecule This is known as Transcription RNA is chemically less stable than DNA and mRNA can be thought of as a temporary copy of DNA s information Transcription Translation Folded Proteins enzymes structural proteins membrane channels hormones signaling molecules Gene DNA segment needed to make a protein Genes are typically 103 104 base pairs in size although they can be much larger For example the human dystrophin gene is 2 x 106 base pairs E coli has about 4 200 genes which isn t very many considering that at least 1 000 different enzymes are needed to carry out just the basic biochemical reactions in a cell The smallest genome for a free living organism i e a cell not a virus is that of the bacterium Mycoplasma genetalium which encodes only 467 genes Humans are at the other end of the spectrum of complexity and have about 20 000 25 000 genes 7 03 Fall 2006 Lectures 1 2 3 of 9 In the demonstration in class you see how a mutation in the Shibire gene in the fly Drosophila gives a heat sensitive protein that is required for synaptic transmission When the flies that carry this mutation are warmed by the projector lamp they become paralyzed Gene Shibire Protein Dynamin Cellular function Vesicle recycling Organismal function Neuromotor activity This example illustrates two powerful aspects of genetic analysis First we can follow microscopic changes in the DNA such as the temperature sensitive mutation in the Shibire gene as they are revealed by the macroscopic consequences of the mutation such as a paralyzed fly Second we have a very precise way of studying the function of individual proteins by examining the consequences of eliminating just that one protein function in an otherwise normal organism Alleles different versions of the same gene Often alleles are referred to as mutants but actually this usage is often incorrect particularly when we discuss naturally occurring variants in a population Mutation an altered version of a gene when we have witnessed the alteration but not when it is preexisting in the population Genotype all alleles of an individual Wild type defined standard genotype The concept of wild type is used as a defined reference for organisms where we can do breeding experiments Of course there is no realistic way to define a standard genotype for humans therefore wild type has no meaning when we discuss human genetics The physical definition of the gene is a very good one but there are many instances where we wish to study genes whose DNA sequences are not known For example say we have isolated a new mutant fly that is also paralyzed and we want to know whether this mutation is also in the Shibire gene We will see in the next several lectures that we can answer this question without knowledge of the DNA sequence either by a test for gene function known as a complementation test or by a test of the chromosomal position of the mutation by recombinational mapping In practice these other ways of defining genes by function or by position are often much more useful than a definition based on the DNA sequence 7 03 Fall 2006 Lectures 1 2 4 of 9 Lecture 2 In this lecture we are going to consider experiments on yeast a very useful organism for genetic study Yeast is more properly known as Saccharomyces cerevisiae which is the single celled microbe used to make bread and beer Yeast can exist as haploids of either mating type a MATa or mating type MAT Haploid cells of different mating type when mixed together will mate to make a diploid cell Haploids and diploids are isomorphic meaning that a given mutation will cause essentially the same change in haploid and diploid cells This allows us to look at the effect of having two different alleles in the same diploid cell All yeast needs to grow are salts minerals and glucose minimal medium From these compounds yeast cells can synthesize all of the molecules such as amino acids and nucleotides that are needed to construct a cell The synthesis of complicated molecules requires many enzymatic steps When combined these enzymatic reactions constitute a biochemical pathway Consider the pathway for the synthesis of the amino acid histidine A Enzyme B 1 C 2 D 3 histidine Protein 4 Each intermediate compound in the pathway is converted to the next by an enzyme For example if there is a mutation in the gene for enzyme 3 then intermediate C can not be converted to D and the cell can not make histidine Such a mutant will only grow if histidine is provided in the growth medium 7 03 Fall 2006 Lectures 1 2 5 of 9 This type of mutation is known as an auxotrophic mutation and is very useful for genetic analysis growth on minimal growth on minimal histidine His wild type His Phenotype All traits of an organism with an emphasis on trait under investigation Homozygote diploid with two like alleles of same gene Heterozygote diploid with two different alleles of same gene Recessive Allele trait not expressed in heterozygote genotype phenotype Mate to diploid genotype diploid phenotype MATa His3 His MAT His3 His3 His3 His MATa His3 His MAT His3 His3 His3 His Based on the His phenotype of the His3 His3 heterozygote we deduce that His3 is recessive to wild type Let s consider a different kind of mutation giving resistance to copper that occurs in a gene known as CUP1 genotype phenotype Mate to MATa Cup1r copper resistant MAT Cup1 diploid genotype Cup1r Cup1
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