MCB 502A - 2014. Lecture #3Genome Evolution. DNA replication— The two major types of genome evolution— Dot-hybridizationDNA replication— The problem of helix unwinding— Various explanations— Following the fate of parental DNA in bacteriophages— Equilibrium centrifugation— The experiment of Meselson and Stahl— The experiment of TaylorThe two major types of genomeevolution-1— The cross-hybridization studiesof DNA from different speciesthat we discussed at the end of theprevious lecture revealed certainpatterns that are easier to operateat the level of "total DNA of thecell", also known as "genome".— In particular, the differencesbetween genomes of differentspecies highlighted thephenomenon of "genomeevolution" that we will discussnext.The two major types of genomeevolution-2— For a long time genome evolution was thought to be driven by pointmutations: one-nucleotide changes in the DNA sequence to gradually adapt to astable environment, with occasional genome scrambling by rearrangements toget a foothold in an entirely new habitat.EnvironmentSelectionMechanism of evolutionGenomes are expected…ConstantStabilizingPoint mutations andsmall rearrangements… to retain their common "frames"Changing/ErraticAdaptation to new ormultiple conditionsLarge-scale intra-genomerearrangements… to be scrambled (nocommon frame preserved)The two major types ofgenome evolution-3— The hybridization studies like theone we discussed, and more recentlythe whole-genome sequencing,produced an entirely different picturefor bacterial genomes.— The bacterial genomes turned outto be much more dynamic andadaptable, but in an unexpected way.— There is a significant "flow ofgenes" from the environment throughthe genomes, as genes are frequentlylost, forcing their homologs oranalogs to be picked up from theenvironment by selection.The two major types of genomeevolution-4— Bacteria internalize relatively longuninterrupted chunks of foreign DNA,apparently for food, …… but sometimes this food ends up beinginserted into the chromosome, becoming partof the genome.— "You are what you eat" is the slogan ofthe prokaryotic genome evolution.The two major types of genomeevolution-5— This process produces "mosaicgenomes" in close relatives.— Such genomes, if compared pairwise,are mostly homologous in that they havethe common "frame", but also containinterspersed homeologous andcompletely heterologous patches ofDNA.— It is remarkable to observe how stablethese genomic frames are through themillions of years of bacterial evolution.— The reason for their stability (referredto as "high synteny" or high degree ofgene colocalization) remains a mystery.The two major types of genomeevolution-6— How is this mode of evolutiondifferent from the classic "graduallymutate and occasionally scramble" modethat yields familiar "evolutionary trees"?— The continuous gene flow throughbacterial genomes means the the mode ofevolution is changed from branching to"festooning".— HGT allows for a faster adaptation to anew environment, as the newcomerbacterium can pick up all the necessarygenes to survive in the new habitat fromaboriginal microbes, as long as the newproteins can be "plugged into" thenewcomer's metabolism.The two major types of genomeevolution-7— The now classic example is thebenign resident of our gut, E. coli,with a typical genome size in the4.2-4.7 Mbp range and a minimal"normal" genome of 3.7 Mbp.— E. coli has enteropathogenicrelatives causing food poisoningwith genome sizes up to 5.4 Mbpthat, apparently, have picked uppathogenic islands of really nastygenes from some other, unrelatedpathogens, allowing these nowdangerous E. coli to colonize varioushabitats within our body.The two major types of genomeevolution-8— This adaptational utility ofhorizontal gene transfer is furtherenhanced by the mobilome —thecollection of genes on theextrachromosomal elements(plasmids and phages) staying for afew, or a few thousand, generationswithin prokaryotic cells.— The two classic examples hereare Bacillus cereus — Bacillusantracis lethal differences in theresident plasmids …… and the Vibrio deadly lysogenicconversion by the XTS prophage.The two major typesof genome evolution-9— Thus, a bacterial genome can take upand accommodate a lot of foreign DNA (inthe above case of E. coli, up to 50% of itsminimal value).— At the same time, the circularity ofbacterial chromosome puts severerestriction on gross chromosomalrearrangements, making many of themnonviable.— By the way, because mobile elementmovement stimulates rearrangements, thisindirectly but severely restricts the numberof mobile elements in the microbialgenomes, by killing off lineages thatcannot control them.The two majortypes of genomeevolution-10— The general patterns of archaealgenome evolution are similar tothose of bacteria and aredominated by rapid gene loss andre-acquisition via horizontal genetransfer, combined withintolerance for active mobileelements (repeats).— This predictably results in highsynteny between related archaealgenomes.The two major types of genomeevolution-11— In contrast to bacteria and archaea,eukaryotic genome evolution is immune tohorizontal gene transfer and instead isdominated by rearrangements.— The reason horizontal gene transfer doesnot work in eukaryotes is that their DNA iskept in a separate compartment (the nucleus),…… while their cytoplasmic routing ofexogenous DNA specifically avoids thenucleus, ……so the exogenous DNA is degraded bycytoplasmic DNases before it has a chance toget to the nucleus and incorporate into thegenome.The two major types ofgenome evolution-12— The major type of exogenous DNA thathas any chance of inserting into theeukaryotic genome is the cDNA ofretroviruses.— Retroviruses are single-stranded RNA(ssRNA) viruses that replicate only in thenucleus via duplex cDNA intermediatesintegrated into the host genome.— Since retroviruses have to get to thenucleus to replicate, while no other DNAcan, retroviral infections is the majorsource of exogenous DNA in eukaryotes.— In addition, because of the uniquebiology, retroviral infections are a majordriver of the eukaryotic genome evolution.The two major types ofgenome evolution-131) The small sizes of theretroviral genomes, …2) the one-enzyme mechanismof retroviral cDNA formation,and …3) the rampant recombinationduring cDNA synthesis …… breed ever-changing familiesof simplistic mobile
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