Brooke Troxell

Dr. Dudycha

BIOL 652: Evolutionary Biology

04 October 2016

Mutation: The Driving Force of Disease Evolution

The largest enemy that humans have faced since our evolution is disease. From viruses

with high mutation rates like the human immunodeficiency virus (HIV) to chronic bacterial

infections like tuberculosis to parasitic protozoa like the Plasmodium species that cause malaria,

pathogens that affect humans utilize different evolutionary mechanisms to stay potent. The main

three phenomena that cause evolutionary change are mutation, migration, and genetic drift.

However, the most effective means of evolutionary change is mutation. Migration and genetic

drift can be powerful for short period of times but mutation gives an organism the power to

continually adapt and evolve.

Mutations are changes in one or many base pairs of DNA. They can be as minute as the

insertion or deletion of a single nucleotide to the loss or fusion of entire chromosomes. Genetic

mutation is a powerful evolutionary force because it is the source of all new genetic information

(Herron et al 2014). Genetic variation is what allows evolution to occur. The frequency of

genetic mutations can have profound consequences on allele frequencies and the maintenance of

Hardy-Weinberg equilibrium (Herron et al 2014). The higher the mutation rate, the more fatal a

disease. The best example of the consequences of an extremely high mutation rate is HIV. This

retro-virus has a mutation rate of 4.1 +/- 1.7 x 10-3 per base per cell (Cuevas et al 2015). The

high mutation rate means that this virus not only changes in between hosts but it can also

develop several strains within one host making it almost entirely impervious to treatment.
Single-drug treatments do not stand a chance against HIV and it can even develop resistance to

multi-drug treatments. In 2012, HIV was the sixth most common cause of death worldwide and

the third deadliest communicable disease (WHO 2014). There is currently no vaccine for HIV

because the mutation rate is so high that by the time a vaccine is produced that strain would no

longer be prevalent in existing populations. A similar situation exists with the influenza virus.

Influenza A and B have mutation rates of 2.0 x 10-6 and 0.6 x 10-6 mutations per cite per infection

cycle, respectively (Nobusawa & Sato 2006). These mutation rates are still fairly high but much

lower than the rate of HIV. This means that effective vaccines can be developed but must be

updated every year, or infection cycle. The Ebola virus from central Africa also has a fairly high

mutation rate of 9.6 x 10-4 substitutions per site per year (Hoenen et al 2015). A high mutation

rate made treatment and the development of vaccines very difficult at the outbreak of this very

fatal virus. The prevalence and notoriety of these diseases is a product of the fact that genetic

variation is a necessity for evolution so organisms with the highest amounts of genetic variation

(i.e. high mutation rates) have the greatest advantage.

Another source of evolutionary change is migration, or the movement of different alleles

between populations of the same species (Herron et al 2014). This means that migration does not

just include the movement of individuals from one population to another, but also the movement

of genetic information such as the transfer of plasmids that is common in populations of bacteria.

The migration of genetic information can vary widely depending on the organism depending on

the mobility of individuals and differences in life cycles (Herron et al 2014). The effects of

migration of allele frequencies also largely depend on the size of populations (Herron et al 2014).

Smaller populations are more likely to have a major shift in allele frequencies with the

immigration of new genetic information from other populations. Large populations are less
likely to experience significant shift in allele frequencies with an immigration from a smaller

population. Migration can also homogenize allele frequencies in different populations if it is not

balanced by another mechanism of evolution (Herron et al 2014). For pathogens that infect

hosts, the hosts genetic variation is just as important as the pathogens genetic variation. An

example is the potency of smallpox as Europeans traveled around the world starting in the

fifteenth century. People living in Europe, Asia, and Africa at the time had been exposed to

small pox for thousands of years at that point and while it could still be fatal or disfiguring, about

70% of people who contracted the disease survived (Greenspan 2015). However, when the

Spanish and Portuguese introduced the virus to the Americas, it had a fatality rate of almost 90%

(PBS 2005). The genetic variation for the hosts of smallpox in the Americas was the direct cause

of its increased fitness. However, since smallpox did not have much genetic variation on its

own, once vaccines were discovered they became a powerful weapon against the virus and

smallpox was declared eradicated in 1980 (Greenspan 2015). The success of migration as an

evolutionary mechanism means relying on the genetic diversity of another population or the

genetic diversity of your host. While this can be an effective strategy, it can also be short-lived,

as we see in the case of small pox, making it not as effective for evolutionary change as

mutation.

Genetic drift is a third mechanism of evolutionary change. Genetic drift is a random,

nonselective mechanism of evolution (Herron et al 2014). It is the phenomenon that allele

frequencies may change in response to the random mating of individuals in a population. Like

migration, genetic drift has a larger effect in smaller populations as the rarity of new alleles

depends on the population size. Genetic drift affects both asexual and sexual organisms as long

as they share genetic information with other members in their population. However, many
diseases such as tuberculosis or malaria require large populations of the pathogen to cause

symptoms and damage. Large populations mean that the chance of a new mutation being in the

few organisms that start a new colony in a new host is low. Pathogens with high mutation rates

escape this set back by have a large percentage of the population constantly mutating, increasing

the chances of spreading new genetic information to new populations.

These evolutionary mechanisms can affect different populations in different ways. For

example, retro-viruses are more likely to have high mutation rates because of the many steps and

places for error required for their replication. Genetic drift can only occur in populations of

organisms that share genetic information with each other. Migration can be viewed at either an

individual or genetic level, but not both for some organisms. Genetic variation is a requisite for

evolution, but for diseases, their genetic variation is not the only variation that matters. The

variation and ability of their hosts to adapt is also key in their fitness and evolutionary trajectory.

Mutation is the most effective evolutionary mechanism because both migration and genetic drift

depend on the variation that it produces. The rate of mutation also influences our ability to fight

the disease; pathogens with higher mutations rates have higher fitness because we are less

effective at treating them.

 Works Cited

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