Mutations and Evolution- Exam II

Micro 4130 Exam 2

Effects of a mutation on fitness

Can be neutral, beneficial, or detrimental. Natural selection determines the effect of a mutation on fitness.

Does a mutation always yield the same outcome

Some mutations always give you the same outcome regardless of environment (for example losing a piece of the ribosome with always result in death). Other mutations depend on the environment to determine if they’re beneficial.

Is the loss of the LamB B-barrel protein beneficial?

Depends on the environment. If the cell needs to import maltodextrins to survive, then LamB is essential. However, if phage can use LamB to attach to the cell and the cell can grow on another substrate, then losing LamB might be beneficial for survival.

Pathway for antibiotic sensitivity

Entry and accumulation, interaction with target, death or growth inhibition.

Antibiotic targets

Must be essential for the antibiotic to be effective

Antibiotic resistance

Can be generated as a result of mutations in any stages of antibiotic sensitivity

Kinds of antibiotic resistance

Decreased entry, increased efflux, target overproduction, target modification, antibiotic modification/destruction, or target bypass

Target bypass

Method of antibiotic resistance. If the cell needs the target to do something, it can evolve a way to get the same process done without using the target.

Decreasing entry via mutations in the preexisting genome

Changing/deleting transporters, modifying the cell surface so the antibiotic can’t associate as easily

Decreasing entry via HGT

Acquire enzymes that modify membranes

Increasing efflux via mutations in preexisting genome

Upregulating production of a specific pump that works well, or modifying existing pumps for specificity

Increasing efflux via HG

Acquire new pumps

Modify target or increase amount via mutations in the existing genome

Modify antibiotic binding site on the target (still needs to function). Use txn factors to upregulate production of the target. Gain ability to work even when bound to target.

Modify target/ increase target amount via HGT

Acquiring modified target that is resistant, or acquiring redundant target that doesn’t interact

Modifying/destroying antibiotic via mutations in preexisting genome

Change existing enzyme so that it can now modify/destroy antibiotic

Modifying/destroying antibiotic via HGT

Acquiring modification/destruction enzymes

HGT vs mutations to preexisting genome

HGT is a much more common way to acquire antibiotic resistance than mutating the preexisting genome

Does selection cause mutagenesis or is mutagenesis random?

Normally the mutagenesis is random and selective pressure maintains the mutations. Some antibiotics can actually cause mutagenesis if they affect replication machinery

How to determine if a mutation is spontaneous or induced by antibiotics

Perform several different selection experiments and look at the number of mutants selected. If the mutations were present in the population before, then the number of mutants will vary (based on when the preexistent mutant arose in the population). If the mutations were in response to the selection, then the number of mutants selected for would be constant.

Are antibiotics mutagenic

In most cases no, but some situations/stressors can induce more mutations!

Are mutation rates across across the genome equal

Not always- in some organisms there can be a mutation frequency difference between essential and non-essential genes. This occurs because certain regions of the genome have evolved to be more protected against mutagenesis than others. More essential genes have evolved to be more protected

How regions of the genome can be protected from mutagenesis

Protein covering to protect against ROS.

common methods of mutagenesis in normal processes

Direct repeats can lead to homologous recombination or deletion. Long strings of the same nucleotide can lead to polymerase mistakes.

Why aren’t all bacteria resistant to antibiotics already

Not all cells have been exposed. Maintaining resistance can be a fitness cost- if no selective pressure, you might passage out resistance over time.

Why can antibiotic resistance be a fitness cost

Plasmids that confer antibiotic resistance are transferred very easily, but they are very large. This means they might not be beneficial for the bacteria in terms of amount of resources required to maintain resistance.