BIOL 1004 Lecture Notes - Genetic Drift, Immunodeficiency

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30 Jan 2013
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o short-term advantage in survival and reproduction
A Correlation between Lethality and Transmission?
Short-sighted evolution is not the only reason HIV infection is fatal
o There is evidence that there are rare strains of HIV exist that kill their hosts more slowly than common strains
Important point is that, alterations to HIV’s genome can render the virus less damaging to the host, but still able to
survive in the host’s body
If the host lives longer, then the HIV population persists longer too
To persist beyond the lifespan of the host, a viral population must at some point colonize new hosts
o This means that there is a second level of natural selection acting on HIV
o First level of selection is the one we have already explored:
There are differences among virions in their ability to survive and reproduce within a given host
o Second level of selection occurs when there are differences among viral strains in their ability to move from one
host to another
Strains that are good at getting transmitted to new hosts will become more common over time; strains
that are bad at getting transmitted will disappear
HIV-2 is less common worldwide than HIV-1
HIV-2 is a related virus that humans acquired from a different primate species
o It is less damaging to its hosts than HIV-1
o Individuals infected with HIV-2 do progress to AIDS, but they do so much more slowly than individuals infected
with HIV-1
The slower course of HIV-2 infection appears to be related to the fact that viral loads are lower in hosts
infected with HIV-2 than in hosts infected with HIV-2
HIV-2’s Nef protin has a function that was lost in HIV-1’s ancestors before they began infecting humans
Nef protein prevents chronic immune activation
o Therefore HIV-2 would not kill its host so easily as HIV-1 does
HIV-2 is also transmitted at lower rates than HIV-1
Differences in transmission rate may explain why HIV-2 has remained largely confined to West Africa,
while HIV-1 has spread across the globe
A second reason why HIV infection is fatal is that the traits that predispose HIV populations to ultimately kill their hosts-
traits like the ability to replicate rapidly, evade the immune system, and maintain large population sizes, may also
enhance HIV’s ability to colonize new hosts
o Selection at the level of host-to-host transmission may favour such traits, even at the expense of killing individual
hosts more quickly \
Therefore the second reason HIV infections are fatal may be that traits that predispose HIV to kill also enhance its ability
to infect new hosts
1.1- Why Are Some People Resistant to HIV?
HIV has relatives called the simian immunodeficiency viruses (SIVs), that infect various species of primates
o Natural hosts of SIVs typically tolerate infection without getting sick
It was discovered that ∆32 allele of CCR5 was the mutation obtained in individuals who survived longer or were
unaffected by AIDS
o It was shown that HIV cannot enter cells that have the ∆32 form of CCR5
In human populations, some individuals carry alleles that make them resistant to infection with HIV
When the frequency of the allele ∆32 was measured, it was discovered that:
o The mutant allele was present at a relatively high frequency of 9% in Europeans but is completely absent in
individuals of Asian or African descent
o CCR5-∆32 allele is common in northern Europe and declines dramatically in frequency to both the south and the
east
Curiously, the frequency of the best-known protective allele is highest in regions with low rates of HIV infection
Two explanations for the uprising of CCR5-∆32:
o The CCR5-∆32 allele may have been recently favoured by natural selection in European populations
o The allele could have risen to high frequency by chance, in a process called genetic drift
It is predicted that the Vikings brought the CCR5-∆32 allele to the Europeans
It appears that HIV is too new a human disease to have triggered substantial evolutionary change in human populations
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