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MIT 7 03 - Genetics Lecture Notes

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Genetics Lecture Notes7.03 2006Lecture 17.03 Fall 2006Lecture 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 DNAFor 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 2006In 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. TranscriptionTranslationGene: DNA segment needed to make a proteinGenes 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. Folded Proteins:enzymes structural proteinsmembrane channelshormones, signaling molecules7.03 Fall 2006In 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 — Protein — Cellular function — Organismal function (Shibire) (Dynamin) (Vesicle recycling) (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 geneOften 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 individualWild-type: defined standard genotypeThe 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


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MIT 7 03 - Genetics Lecture Notes

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