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BIO207H5 (42)

ch 4: gene function

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University of Toronto Mississauga
Karen Williams

Ch4 Gene Function Gene control of enzyme structureGarrods hypothesis of inborn errors of metabolism 1902 Archibald Garrod an English physician studied alkaptonuria a human disease characterized by urine that turns black upon exposure to air and buy a tendency to develop arthritis later in lifegenetically controlled trait Garrod found that people with alkaptonuria excrete homogentisic acid HA in their urine whereas people without the disease do not HA is what turns the urine blackthis result indicated to Garrod that normal people can metabolize HA but that people with alkaptonuria cannotthis disease is an example of an inborn error of metabolismthat is alkaptonuria is a genetic disease caused by the absence of a particular enzyme necessary for HA metabolism Garrod work provided the first evidence of a specific relationship between genes and enzymes another important aspect of Garrods work wasthe position of a block in a metabolic pathway can be determined by the accumulation of the chemical compound that precedes that blocked step The onegeneoneenzyme hypothesis 1942 George Beadle and Edward Tatum heralded the beginnings of biochemical genetics a branch of genetics that combines genetics and biochemistry to explain the nature of metabolic pathwaysresults of their studies involving the haploid fungus Neurospora crassa orange bread mold showed a direct relationship between genes and enzymes and led to the onegeneoneenzyme hypothesis direct relationship between genes and enzymes Isolation of Nutritional Mutants of Neurospora Neurospora has important properties that make it useful for genetic and biochemical studies including the fact that it is a haploid organism so the effects of mutations may be seen directly and that it has a short life cycle enabling rapid study of the segregation of genetic deficits simple growth requirements of Neurospora were important for Beadle and Tatums experiments Wild type Neurospora grows on a minimal medium simplest set of chemicals needed for the organism to grow and surviveA strain that can grow on the minimal medium is called a prototrophic strain or a prototroph Beadle and Tatum reasoned that Neurospora synthesized the other materials it needed for growth ex Amino acids nucleotides vitamins nucleic acids proteins from the simplest chemicals present in the minimal medium Beadle and Tatum realized that it should be possible to isolate nutritional mutants auxotrophic mutants or auxotrophs of Neurospora that would not grow on minimal medium but required nutritional supplements to grow Beadle and Tatum isolated and characterized the auxotrophic mutants To isolate auxotrophic mutants Beadle and Tatum treated conidia with Xrays An xray is a mutagen mutation generator an agent that induces mutants They crossed the mutants they obtained with a prototrophic wild type strain of the opposite mating typeby crossing the mutagenized spores with the wild type they ensured that any auxotrophic mutant they isolated was heritable and therefore had a genetic basis rather than a nongenetic reason for requiring the nutrient the researchers allowed one progeny from the crosses to germinate in a nutrionally complete mediuma medium containing all the amino acids purines pyrimidines and vitamins in addition to the sucrose salts and biotin found in minimal medium
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