Evolution of Human Health

What is the evolution of resistance? What are “resistance genes”?

Humans use a toxic substance to kill another species (ex: weeds = plant “pests” or cancerous tissues) —→ Strong positive selection favoring any alleles that reduce the effects of the toxin (= “resistance genes”) —→ “Selective sweeps” of resistance genes to high frequencies in pathogen, pest, or cancer population (fixation of resistance genes/alleles) —→ Toxic substance doesn’t control pathogen, pest, or cancer population anymore

What is the difference between using antibiotics vs vaccines to fight off bacteria?

With antibiotics, resistance will always evolve against antibiotic. As for vaccines, some bacteria, such as the coronavirus, will not evolve to fight against vaccine (killing off disease for good)

Provide a few examples of “resistance mutations” that can allow bacteria to survive antibiotic exposure.

• Germs change or destroy antibiotic using enzymes

• Germs change the antibiotic’s target (receptor) so that the drug can no longer fit and do its job

• Germs get rid of antibiotic using pumps

Briefly describe the rapid change of the leading causes of death from the 1900 to 1997 to modern-day.

1900: Infectious disease was the leading cause of death in the USA

1997: Discovered antibiotics

Modern-day: Developed vaccines and have better hygiene these days

What has widespread use of antibiotics and antifungals lead to? What are these types of pathogens called?

The evolution of pathogen strains that are resistant to all drugs.

• Superbugs = strains of bacteria or other pathogens that are resistant to all commonly-used antibiotics or antifungal drugs

What are a few possible way that superbugs can develop?

• Cells could have grabbed DNA from their environment (HGT)

What are the reasons as to why bacterial populations rapidly evolve resistance?

1. Long history of exposure to chemical warfare

2. Short generation times (→ rapid evolution)

3. Enormous population sizes (→ more resistance mutations)

4. Strong selection from overuse/misuse of antibiotics

5. Lots of gene flow (due to enormous population sizes + high mobility of bacteria and their genes)

6. Horizontal transfer of resistance genes (HGT)

7. Bacterial stress responses to antibiotics → higher mutation rate (high chance of resistant mutations)

What is Horizontal Gene Transfer (HGT)? What has this ability led to?

When two individuals right now can exchange genes with each other or the environment. HGT has led to resistance genes that can “jump” between individual cells & among lineages

What are the different mechanisms of HGT?

1. Conjugation

2. Transformation

3. Transduction

4. Vesiduction

What is stress-induced mutagenesis (SIM) in bacteria? What are examples of stressful conditions?

Mutation rates can sometimes increase (“stress response”) when bacteria are under stressful conditions → less accurate DNA replication and/or reduced DNA repair

Some examples: starvation, UV exposure, exposure to antibiotics

SIM → higher mutation rates → more resistance mutations

What are hypotheses for why some bacteria have evolved SIM?

1. Unavoidable side-effect of mechanisms that allow bacteria to survive in stressful conditions

   1. unavoidable cost of increased replication error & reduced DNA repair

2. It’s indirectly favored by natural selection

   1. (//)

What are “somatic” mutations? What is somatic evolution?

Mutations that can affect survival or replication rates of cell lineages. Any “somatic” mutations that arise in a cell are passed on to its descendants. Somatic evolution are when cells with higher survival and/or faster replication come to dominate tissues

Resistance mutations often come with a (- - -)

Fitness cost

• In the presence of antibiotic or chemotherapy, benefits outweigh the costs and resistant cells have higher fitness than susceptible cells

• But in the absence of antibiotics, a susceptible cells will have higher fitness than resistant cells, if there’s a fitness cost

Things that can control the growth bacteria populations within a host include:

• Antibiotics

• The host’s immune system

• Natural enemies of bacteria (like bacteriophages)

• Competition for resources with other bacteria

If there’s a fitness cost to resistance, what can susceptible bacteria do in the absence of antibiotics? What is this called?

Competition from susceptible bacteria can help suppress the growth of resistant bacteria in the absence of antibiotics. It can maybe even reduce their numbers. This is called “competitive control”

How do antibiotics effect different bacteria populations? What is this called?

Antibiotics use can increase the growth rate of resistant bacteria by wiping out their competitors (susceptible populations). This is called “competitive release”

What can competitive release from killing susceptible bacteria using antibiotics do?

1. Allow rapid growth of resistant forms of the targeted pathogen (possibly making the targeted infection even worse)

2. lead to a new harmful infection by eliminating competitors that were holding another type of pathogen in check

3. Increase the production of resistance genes, which can then spread through the environment & to other strains of bacteria

What are things that can control cancer cell population growth?

• Chemotherapy or other treatments

• Host’s immune system - will identify and kill bad cells

• Competition (from other cancer cells and non-cancerous cells)

In cancers, there’s often a fitness cost to resistance:

• In the absence of treatment, resistant cells grow more slowly than susceptible cells

How can chemotherapy increase the growth rate of resistant cancer cells?

Because cells within a cancer compete for resources, if chemo is administered, then it will wipe out all of the susceptible cancer cells (and weaken the immune system), which will increase the growth rate of resistant cancer cells

What is “phage therapy”?

Use host-specific bacteriophages to kill off pathogenic bacteria in sick humans

• “Arms Race” b/w phages and bacteria

What are the potential advantages of phage therapy over antibiotics?

1. Phages can evolve (may be able to coevolve to overcome phage-resistance that arises in bacteria)

2. Phage host specificity - phages often only kill one specific type of bacteria (won’t kill the “good” bacteria in a host"); no “competitive release”

   1. Whereas antibiotics kill both good and bad bacteria in host

3. Possible trade-off: If bacteria does evolve to the point of phages not working anymore, then the bacteria must give up their antibiotic resistant gene

   1. So we good :)))