Genetic Exchange Notes 2024 PDF

+-----------------------------------+-----------------------------------+ | Bacterial Genomes and Mobile | | | Genetic Elements | | +-----------------------------------+-----------------------------------+ |...

+-----------------------------------+-----------------------------------+ | Bacterial Genomes and Mobile | | | Genetic Elements | | +-----------------------------------+-----------------------------------+ | | - bacteria live in multispecies | | | biofilms in the microbiota | | | | | | - pathogenic bacteria often | | | form monospecies biofilms and | | | sometimes multispecies | | | biofilms on indwelling | | | devices (e.g., catheters, | | | joint replacements) | +-----------------------------------+-----------------------------------+ | | - know this | | | | | | - it is an aecology | +-----------------------------------+-----------------------------------+ | | - most microbiota is mixed | | | species | | | | | | - they are a highly adapted | | | ecology of bacteria | | | | | | - they often contain biofilms | | | (learn about in next section | | | of M2C) | +-----------------------------------+-----------------------------------+ | | - know this | | | | | | - resident microbiota is your | | | own microbiota | | | | | | - transient microbiota comes | | | and goes | +-----------------------------------+-----------------------------------+ | | - Dysbiosis is a microbial | | | imbalance in the microbiota | | | | | | - Many things influence | | | microbiota including diet, | | | exercise, antibiotics and | | | hygiene | | | | | | - Dybiosis can lead to changes | | | in immune status including | | | inflammation (hyperimmunity) | | | and immunodeficiencies as | | | well as possibly autoimmune | | | diseases | | | | | | - This can lead to chronic | | | systemic inflammation and | | | metabolic disease | | | | | | - Hygiene means too much | | | hygiene | +-----------------------------------+-----------------------------------+ | | - GI microbiota is being shown | | | to contribute to multiple | | | conditions | | | | | | - These include system | | | conditions such as diabetes. | | | Obesity was shown not to be | | | largely influenced by | | | microbiota. | | | | | | - Local conditions such as | | | Crohn's disease and colon | | | cancer | | | | | | - Gut-Brain Axis, GI microbiota | | | may influence psychological | | | conditions as well as | | | Parkinson's disease | | | | | | - Vagus nerve connects the | | | brain and the butt | +-----------------------------------+-----------------------------------+ | | - Know this | | | | | | - Pathogens are found in the | | | microbiome meant to murder | | | | | | - | +-----------------------------------+-----------------------------------+ |  | - know this | | | | | | - to be marked by phylogneny | | | there needs to be a mark to | | | go through evolution | | | | | | - phylogeny assuming an | | | ancestor and using evolution | | | to change gene seq | +-----------------------------------+-----------------------------------+ | | - The bacteria are organized | | | into Kingdom, Phylum, Class, | | | Order, Family, Genus, Species | | | | | | - Species are at the end of | | | each branch | | | | | | - There are 3 kingdoms based on | | | ribosomal rRNA gene | | | phylogeny. Other trees can be | | | made based on physical | | | functions and characteristics | | | | | | - Phylum are usually composed | | | of 50-100s of different | | | bacteria. Due to high | | | bacterial person-to-person | | | microbial diversity | | | microbiota studies are done | | | at the Phylum, Family and | | | Genera level assuming common | | | properties of all bacteria | | | within the group are | | | important for health and it | | | doesn't matter which species, | | | as long as a microbiota | | | member fulfills that activity | +-----------------------------------+-----------------------------------+ | | - know this | | | | | | - commensensals will have | | | different SNPs- no mobile | | | genetic info | +-----------------------------------+-----------------------------------+ | | - bacteria usually have single | | | circular chromosomes | | | (although occasionally | | | bacteria will have linear | | | chromosomes) | | | | | | - bacteria are haploid, so | | | mutations can be expressed in | | | the next generation | | | | | | - single nucleotide | | | polymorphisms | | | | | | - random mutation rate due to | | | uncorrected errors from DNA | | | polymerase during replication | | | 1 in 10^6^ genes/generation | | | | | | - not all mutations will | | | lead to a phenotype | | | | | | - mismatch repair can decrease | | | mutations about about 2 logs | | | 1 in 10^8^ genes/generation | | | | | | - under stress this increases | | | due to error prone | | | polymerases | | | | | | - this is where SNPs come from | | | | | | - haploid there is no different | | | phenotype- once a mutation is | | | found it expresses it | +-----------------------------------+-----------------------------------+ | | - error prone polymerases lack | | | proofreading capabilities, | | | allowing them to read past | | | lesions by randomly inserting | | | nucleotides | | | | | | - important under conditions of | | | stress | | | | | | - increased mutation rates | | | under stress such as | | | oxidative damage (e.g. | | | oxidative burst by immune | | | cells) | | | | | | - starvation (in deep | | | layers of a biofilm) | | | | | | - error prone pol. do not | | | proofread | +-----------------------------------+-----------------------------------+ | | - types of horizontal gene | | | transfer (HGT) | +-----------------------------------+-----------------------------------+ |  | - Transformation is the uptake | | | of DNA from the environment | | | by competent bacteria | | | | | | - because the DNA is free | | | in the environment the | | | DNA is sensitive to DNase | | | | | | - inhibition of DNA uptake | | | by DNase during | | | laboratory experiments is | | | a hallmark of | | | transformation | | | | | | - Only competent bacteria can | | | take up the DNA | | | | | | - naturally occurring state | | | | | | - chemically induced in | | | some bacteria | +-----------------------------------+-----------------------------------+ | | - DNA is taken up as a single | | | strand (ssDNA) by DNA uptake | | | machinery | | | | | | - This complex often has pili | | | associated with it | | | | | | - RecA will coat singe strand | | | and do homology search and | | | compared it chromsosme & will | | | replace it | +-----------------------------------+-----------------------------------+ | | RecA mediated homologous | | | recombination | | | | | | - once inside the cell the DNA | | | is protected by ssDNA binding | | | proteins | | | | | | - RecA recombinase binds to the | | | ssDNA and mediates homologous | | | recombination | | | | | | - the ssDNA must have regions | | | of homology to DNA already in | | | the chromosome | | | | | | - in these stretches the DNA | | | will bind and RecA will | | | mediate strand exchange | | | | | | - as long as the DNA is not | | | cleaved by restriction | | | enzymes (enzymes that cleave | | | DNA), it will be incorporated | | | into the genome | | | | | | - numerous additional genes can | | | be introduced into the | | | chromosome as long as they | | | are flanked by regions of | | | homology | +-----------------------------------+-----------------------------------+ | | - a bacterial species with a | | | supragenome (pan genome) will | | | have a core genome that will | | | be shared by all the bacteria | | | (comprises 60-70% of the | | | genome) | | | | | | - it will then have distributed | | | genes | | | | | | - genes present in only | | | some of the bacteria in | | | the population | | | | | | - gives rise to different | | | strains | | | | | | - genes encoded unique | | | functions -- alternate | | | metabolism, virulence | | | factors, etc. | | | | | | - transformation is one genetic | | | mechanism that can give rise | | | to this type of genome | | | structure in a species | +-----------------------------------+-----------------------------------+ | | - transformation of competent | | | cells lead to the discovery | | | of DNA | | | | | | - *Streptococcus pneumoniae* is | | | a virulent bacteria that will | | | kill mice | | | | | | - *S. pneumoniae* requires a | | | capsule to keep it from being | | | killed by the immune system | | | | | | - without capsule it is | | | avirulent (cannot cause | | | disease) | | | | | | - if killed encapsulated | | | virulent bacteria are | | | injected into a mouse along | | | with live avirulent | | | unencapsulated bacteria, the | | | mouse will die because the | | | live bacteria pick up the | | | capsule gene via | | | transformation | +-----------------------------------+-----------------------------------+ | | - know this | +-----------------------------------+-----------------------------------+ | | - Plasmids replicate separately | | | from the chromosome = | | | autonomous replicons | | | | | | - Replication initiation | | | proteins binds to the origin | | | of replication and initiates | | | replication | | | | | | - The bound replication | | | initiation protein recruits | | | the DNA polymerase, which | | | replicates the chromosome, to | | | replicate the plasmid. | | | | | | - Plasmids can have low or high | | | copy numbers and the copy | | | number can be regulated in | | | response to environmental and | | | cell growth conditions | +-----------------------------------+-----------------------------------+ | | - know this | | | | | | - f-plasmid; fertility plasmid | | | | | | - F+: with plasmid | | | | | | - F-: without plasmid | +-----------------------------------+-----------------------------------+ | | - know this | | | | | | - inside of donor: machine to | | | read ATP to push DNA to | | | inside of cell | | | | | | - | +-----------------------------------+-----------------------------------+ |  | - know this | +-----------------------------------+-----------------------------------+ | | - Some conjugative plasmids can | | | integrate into the bacterial | | | chromosome forming Hfrs (high | | | frequency recombination) | +-----------------------------------+-----------------------------------+ | | - know this | +-----------------------------------+-----------------------------------+ | | - plasmid can be detected on | | | agarose gel. | | | | | | - depending on the size of the | | | plasmid they can either | | | migrate through the agarose | | | gel faster or slower than the | | | chromosome | +-----------------------------------+-----------------------------------+ |  | - broad host range plasmids can | | | mediate horizontal gene | | | transfer through numerous | | | genera and species | +-----------------------------------+-----------------------------------+ | | - In bacteria CRISPR-Cas | | | systems (the basis of gene | | | editing) protect commensal | | | bacteria from acquiring genes | | | from horizontal gene transfer | | | | | | - The bacteria are highly | | | adapted to their niche and do | | | not want the burden of extra | | | genetic material, unlike | | | pathogens, that often collect | | | virulence factors and | | | antibiotic resistance genes | | | on mobile genetic elements | +-----------------------------------+-----------------------------------+