Chapter 14: Evolution and Human Health

Introduction

Mutation - rare mutation for resistance genes
Natural Selection - resistant individuals have higher fitness in environments with the drug

Virulence: how harmful a pathogen is to its host depends on natural selection and migration (transmission)
Decreased opportunities for migration can make virulence less adaptive

Individuals vary (polymorphism) and these heritable variations contribute to drug efficiency
Many diseases are evolutionary in nature (infectious disease and cancer)
Vaccine strategies must be understood in terms of the evolutionary response of infectious agents
Disease pathology and progression are correlates of virulence (which is often an evolved strategy)
Darwinian Medicine: the application of Darwin’s theory of Natural Selection to the study of health-related phenomena

Virulence: the damage inflicted by a pathogen on its host
Harm to the host can be adaptive
- Parasite activities decrease a host’s fitness
Virulence occurs
- Parasites using host resources (Malaria eats hemoglobin)
- Evading the immune system (HIV, flu)
- Competing with other pathogens (polio, meningitis)
- As a result of the host’s defense (cold, flu)

Costs: harms the host
- high virulence with decrease the probability that the host will walk/run/jump/fly to a new host and transmit the pathogen
- If the human dies so does the pathogen
Benefits: increase pathogen reproduction
- High virulence means high use of host resources which leads to an increased replication rate of pathogen
- The higher the replication rate the greater the probability that the pathogen will be transmitted to a new host

Coincidental evolutionary theory: virulence in one host is a by-product of selection on other traits
- tetanus produces a neurotoxin, a result of selection in the life in the soil, not the host

Short-sight evolution hypothesis: The pathogen enjoys short-term advantages in survival and reproduction but speeds up the death of the host
- HIV
- Polio (Evolves to infect CNS which kills the host and so the parasite doesn’t gain transmission as a result)
- Achieves within-host competition but loses overall by killing the host

Trade-off hypothesis: there is a trade-off between transmission and virulence
Transmission requires opportunities for pathogens to spread to a new host
Many transmission opportunities
- Contact with potential host
- Can transmit quickly
- favors high virulence
Few transmission opportunities
- Contact with a few potential host
- Must live a long time to have transmission opportunities
- favors low virulence
Example 1: 2 Modes of transmission
- Vertical Transmission: (HIV, some STIs) transmitted from parent to offspring, the host must live to reproduce, low virulence
- Horizontal Transmission: Spread to any other individual rapidly, favors high virulence
Example 2
- Water or Vector-borne pathogens: rapidly spread without contact between hosts, favor high virulence
- Direct Transmission: Direct contact is required between hosts for transmission, the host must remain active, favors low virulence
In general, if a pathogen can spread quickly it can afford to have negative effects on the host (high virulence), but if a pathogen cannot spread quickly it needs to keep the host around for a while (low virulence).
The evolution of virulence depends on the rate of pathogen spread which depends on pathogen ecology (transmission mode) and host behavior (contact with others, sanitation, control of vectors)
Decreasing the disease spread (migration) can make virulence less adaptive.
- Controlling mosquito outbreaks
- clean water
- washing hands
- preventing STD spread

The host wants to kill the pathogen
The pathogen quickly evolves
- Large population
- short generation time
- rapid replication
- high mutation rate
selection imposed by the host immune system favors pathogens that can evade

Influenza A kills 20,000 Americans a year
During the 1918 flu epidemic, it killed 50-100 million people
The virus genome is extremely simple.
- 8 RNAs encode 13 proteins
- Polymerases
- structural proteins
- coat proteins
The coat protein Hemagluttinin functions in attachment and penetration
- this is recognized by the host immune system
Neuraminidase (coat protein) functions in cleaving sialic acid from Hemagluttinin and facilitates the elution of progeny virions from infected cells
Influenza Antigenic Shift: gradual accumulation of mutations allows hemagglutinin to escape neutralizing antibodies.
- Epidemic strains are thought to have changes in 3 or more antigenic sites
Walter Finch et al. (1991)
- Antigenic sites in hemagglutinin proteins evolved a million times faster
- The nucleotide substitution rate was 6.7 x 10^-3 nucleotides per year
- Most of the frozen sample was from an extinct branch
- The surviving lineage was from a single ancestor from 1968
- Hypothesis: surviving linage had an increased fraction of amino acids in its antigenic sites