Evolution and Human Health

Cholera epidemic in 1854

lethal diarrhea and consequently dehydration

John Snow in 1855 prepared a map of affected neighborhood, revealing victims and water pumps

Germ Theory

Early discoveries

Inspired by Pasteur, other scientists found bacteria responsible for anthrax, gonorhea, tb

Robert Koch in 1883: vibro cholerae

Louis Pasteur in 1858 proposed that diseases were caused by microorganisms

Led to identification of pathogens

Infection-fighting developments

antiseptic surgery

discovery of antibiotics

improvements in sanitation

Evolving Pathogens

pathogens have evolved in response to selection pressures imposed by medicine

antibiotics: chemicals that kill bacteria

penicillin

first antibiotic

saved thousands of lives

Today is ineffective against bacteria that previously were highly vulnerable

Select for resistance in bacteria

Frequency of antibiotic resistance tracks changes in the number of prescriptions

Cost of resistance in bacteria

a. resistance rates fell in Iceland when Penicillin use dropped, suggesting that resistance imposes a cost on bacteria

b. if resistance comes at a cost, then in the absence of antibiotics, sensitive bacteria will have higher fitness

c. However, the cost does not always persist

d. resistant bacteria can get equal in fitness compared to sensitive ones, even in the absence of antibiotics

Study: Scrag et. al. 1997

a. Studied streptomycin-sensitive E. coli and screened for resistant mutants

b. Streptomycin interferes with protein synthesis by binding to a ribosomal protein (rpsL)

c. But point mutation in rpsL provided resistance to streptomycin

d. Competed resistant and sensitive strains against each other

initially: resistant strains at disadvantage

Later: resistant strains evolved, and new mutations compensated for the cost

e. With time, the resistant strains outcompeted sensitive strains

Avoiding evolution of resistance:

reducing antibiotic usage might not restore vulnerable bacterial population

thus, steps to avoid bacteria from developing resistance need to be taken:

reduce infection rate

limit use of antibacterial soaps and cleaners

Design and use drugs that target few bacteria

antibiotic use in animal feed should be eliminated

Change in frequencies of genotypes within a population

populations of pathogens and host are in conflict

Pathogens: want to consume host to make more pathogens

Host: wants to kill and and protect itself from pathogens

Pathogens naturally evolve responses:

large population size

short generation times

high rates of mutation

evolve quickly

Is selection imposed by the human immune system responsible for detectable evolution in populations of influenza A viruses?

Influenza A:

responsible for annual flu epidemics

genome composed of 8 RNA strands that encode 13 proteins

ordinary season in the USA kills ~20k people

1918 epidemic:

affected 20% of world pop

within a few months, killed ~50-100 million people

has two major surface proteins:

Hemagglutinin:

Neuraminidase

Main viral coat protein

primary protein recognized and attacked by host immune system

Must survive by one of two of these:

constantly finding new host that doesn't recognize hemagglutinin

altering its hemagglutinin

Flu Virus Evolution

virus has antigenic sites (sites recognized by immune system)

hemagglutinin has 5 antigenic sites

viruses with novel antigenic sites should have a selective advantage

Study: Fitch et al (1991): Mutations on antigenic sites

examined frozen flu virus strains from 1968-1987

flu virus evolves ~1 million times faster than humans

estimated rate of evolution and phylogeny from samples

found two patterns:

  1. Most flu samples examined represented side branches of one main evolutionary tree
  1. Surviving flu strains evolved at a steady rate

Expected and found: Main strain would have had more mutations in the antigenic sites than the extinct strains

Increased variability in antigenic sites gave surviving strain an advantage

Human immune system does exert strong selection on flu virus hemagglutinin genes and virus populations evolve in response

Origin of pandemic flu strains

Radical alteration of hemagglutinin genes

Nucleoprotein gene most important for determining host specifity

strain evolutionary history determined by building phylogeny

each hemagglutinin/neuraminidase group constitutes a clade

Flu strains can have some closely related and some distantly related genes because of horizontal gene transfer

If a host is infected with two different strains, these strains can swap RNA strands

potential for new strains

very novel hemagglutinin genes

leads to pandemic!

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