Benzer s question Add to reading How is complementation between mutants from p444 Deletions remove material to p449 Duplications add material but not pp445 447 Benzer s question How are functional alleles related to recombination between mutants Benzer s question How does the genetic map between the cis acting heritable functional units compare to genetic maps within the cis acting heritable functional units related to segregational alleles He needed AND HAD a selective genetic system with extremely high resolving power for small map distances the large scale map generated by recombination between mutants in different genes as complementation groups Simple cheap fast and POWERFUL 1 the fine structure map of rIIA rIIB generated by recombination between mutants in the same genes as complementation groups 1 612 INDEPENDENT mutants mapped for Fig 7 21 and ultimately 3000 Benzer s intragenic map 1 A linear series of discrete points hence topologically no different than intergenic maps 2 Points not necessarily closer within a gene than between 3 Based on the physical size DNA base pairs of T4 and the total map distance around the T4 map adjacent points estimated to be 2 bp apart hence recombination appears possible between adjacent bp it must be an incredibly precise process to reconstruct wt Remember 1 this was at a time before the nature of the genetic code had been determined 2 A genetic map is an abstraction a representation of meiotic event frequency but the correspondence between the genetic map and DNA had to be meaningful B A Benzer had 1 defined true point mutations segregational alleles 2 developed deletion mapping 3 discovered the lack of any qualitative topological difference between the maps of genes vs chromosomes 4 clarified the relationship between functional allelism complementation the cis trans test and segregational allelism recombination 5 discovered mutational hot spots 6 established that although genes were divisible by recombination they were not infinitely divisible and the lower limit appeared to be the DNA base pair The fine structure map of rIIA rIIB is a valuable tool for further research into the nature of genetic information 7 Set up a genetic system a map that could be exploited to discover a huge amount about the genetic code and informational suppressors without any biochemistry and all without having a clue what rIIA rIIB did for T4 B A rIIB frameshifting point mutations Consequences of deleting the boundary on the genetic map between rIIA and rIIB informational suppressors Fig 8 32 Fig 8 5 2 revertables point mutants Drosophila genetic map nonrevertables deletions no yes yes yes yes yes yes ASK any wildtype recombinants generated from hybrid between 1011 revertable and particular nonrevertables 1011 This is only one kind of deletion mapping based on segregational allelism Deletion mapping based on complementation Drosophila genetic map Drosophila physical map giant polytene chromosomes Deletion mapping based on complementation w rst fa w mutant phenotype failure to complement Df 1 256 45 hence white is within region deleted phenotype Bulge in the synapsed polytene chromosomes shows what is deleted Drosophila physical map giant polytene chromosomes a portion of chromosome 3R The complementation test as an operational definition of the gene is not quite as straightforward as it may sound genes can have very complex complementation patterns because of all the various kinds of information they contain that work in cis scale deletions not easily visible unless 2 3 genes can be up to 250 genes Fig 14 8 p277 Heading rII regon has two genes Is this statement compatible with the statement that complementation groups are what we want to call genes p291 A gene is not simply the DNA that is transcribed into the mRNA codons specifying the amino acids of a particular polypeptide Rather a gene is all the DNA sequences needed IN CIS for expression of the gene into a polypeptide product A gene therefore includes the promoter sequences that govern where transcription begins and at the opposite end signals for the termination of transcription A gene also includes sequences dictating where translation starts and stops In addition to all these features eukaryotic genes contain introns that are spliced out of the primary transcript to make the mature mRNA Because of introns most eukaryotic genes are much larger than prokaryotic genes So promoters are part of genes Are they part of complementation groups 3 the fine structure map of rIIA rIIB generated by recombination between mutants in the same genes as complementation groups A bacterial promoter cis acting information for transcription start 51 bp 1 612 INDEPENDENT mutants mapped for Fig 7 21 and ultimately 3000 transcript Fig 8 12 B A Figure 17 5 The Lactose Operon in E coli rII makes a polycistronic mRNA rII A There are 12 bp between rIIA rIIB genes T4 has 168 903 total bp rII complementation map of point mutants a very different kind of map 7 23 rIIA B promotor mutants rII A 3 5 66 71 rII B 2 65 87 99 three complementation groups No one complex complementation group one gene rII B an example of polycistronic mRNA Eukaryotic genes are even messier Alternative pre mRNA splicing is what allows Drosophila DSCAM gene to make 30 000 different proteins 6 vs 7 8 alternative exons introns and the regulatory regions non protein coding can extend enormous distances on both sides exons Fig 8 18 4 NATURE 184 1927 29 1959 These are the mutants that argue for one gene with a complex complementation pattern 14 31 What are the genes What is the nature of the elements of heredity that Mendel postulated as purely theoretical units Frankly these are questions with which the working geneticist has not much concern himself H J Muller in 1932 published a classic review of how mutations change gene function without even knowing what genes were at the chemical level and he did this in part so that he might What are the genes What is the nature of the elements of heredity that Mendel postulated as purely theoretical units Frankly these are questions with which the working geneticist has not much concern himself true but a bit of sour grapes T H Morgan The Relation of Genetics to Physiology and Medicine Nobel Lecture June 4 1934 Mutations changes in DNA the lifeblood of genetic analysis 1 What kinds can we make categories 2 How do we make them mutagenesis 3 How do we find them mutant screens selections infer what kind of chemicals they had to
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