Lecture17_18 - 3/18/11 Lectures 17 & 18 The Mechanisms of...

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3/18/11 1 Lectures 17 & 18 The Mechanisms of Bacteria Evolution Outline of Lectures • Bacterial population structures: - non-clonal vs clonal bacterial populations - lateral (horizontal) gene transfer (LGT) • Substitution rate, mutation rate, and mutators • Reductive evolution and its consequences in bacterial genomes • Evolution of antibiotic resistance Bacterial Biodiversity • Studies of the biodiversity of bacterial pathogens have yet to be fully exploited in the fight against infection. • Population studies have been hindered by: - poor isolate characterization techniques; - inappropriate isolate collections (concentration on isolates from invasive disease) - lack of integration of theoretical frameworks.
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3/18/11 2 In vitro Studies of Bacterial Evolution Have Been Highly Informative (> 20,000 Generations of Evolution In Culture) • Adaptive evolution is frequent and rapid Rich Lenski Forces Shaping Bacterial Diversity Bacterial diversity mutation Genetic exchange Selection Stochastic events The Clonal Evolution Model • Bacterial reproduce by binary fission (i.e. they are asexual) • Mother and daughter cells are identical (clones) except in the rare case of mutation. • The inability of mutational variation to move between cells other than by descent results in clonal lineages. • Genetic variation among lineages is not random. • Diversity reduction events will purge variation from the population.
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3/18/11 3 Asexual Reproduction and its Consequences Asexual Reproduction and its Consequences Diversity reduction: selective sweeps population bottlenecks Original genotype Mutant genotype Clonal population: highly structured Features of Clonal Populations Linkage disequilibrium: - non-random allele combinations. Low genetic diversity: - limited allele combinations. Tree-like phylogeny: - a bifurcating tree accurately models descent. Congruence: - the same phylogenetic signal is recorded throughout the genome (no “mosaic” genes).
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3/18/11 4 Departures from Clonality • Molecular data reveal that, for many (perhaps most!) bacteria, at least some of the features of clonality are violated. • What is wrong with the clonal model? • It is now well established that bacteria are not wholly asexual - a degree of horizontal genetic exchange (i.e. recombination) occurs. Multi-Locus Sequence Typing (MLST) • Maiden et al . Proc.Natl.Acad.Sci.USA 95 , 3140-3145 (1998). The comparison of complete genome sequences is increasingly commonplace Genomics of Yersinia pestis (plague) • Analysis of 933 single nucleotide polymorphisms (SNPs) • Greatest genetic diversity in China, supporting a Chinese origin • Morelli et al . Nat.Genet . 42 , 1140-1143 (2010).
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3/18/11 5 Horizontal genetic exchange ('localized sex') Original genotype Recombinant genotype Horizontal Genetic Exchange (Recombination) Mutant genotype Horizontal Genetic Exchange (Recombination) • Several mechanisms permit recombination in localized regions of the bacterial genome.
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This note was uploaded on 05/03/2011 for the course BIOL 497A taught by Professor Eddieholmes during the Spring '08 term at Pennsylvania State University, University Park.

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Lecture17_18 - 3/18/11 Lectures 17 & 18 The Mechanisms of...

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