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Terms in this set (60)
the ________ evolved to fight pathogens millions of years ago
human immune system
Our immune system is NOT designed to battle the pathogens that are present in our environment today
what is the strongest selection pressure known? why?
non-protective genes are removed from the environment (LETHAL!)
what is the red queen hypothesis?
organisms must constantly adapt, evolve and proliferate not merely to gain a reproductive advantage, but also simply to survive while pitted against ever-evolving opposing organisms in an ever changing environment
red queen describes to Alice that in order to stay in wonderland you had to keep running as fast as possible to stay in the same place...a population has to constantly keep adapting because the pathogen that is attacking it is also adapting
red queen hypothesis
________ is determined by an array of alleles
if the complete outcome of a viral infection was decided on the basis of a single host antiviral gene... then
the differences in tempo of viral versus host evolution would make it unlikely that the hosts could ever adapt away from a viral infection
the host-virus interaction is COMPLEX!
he outcome of a particular viral infection on a population level is determined by ...
the compendium of antiviral genes borne by
the viral fitness cost associated with escape from antiviral genes
many factors beyond host and viral genetics.
detecting ancient selection example
1) retrovirus enters host cell
2) reverse transcriptase converts the retroviral RNA genome into double-stranded DNA
3) viral DNA migrates to the nucleus and becomes integrated into the host genome
4) viral genes are transcribed and translated
5) new virus particles assemble, exit the cell, and can infect another cell
_____ integrates its genome into the host cell
what is the TRIM5 gene?
a restriction factor that prevents infection from non-host-adapted retroviruses
blocks viral infection early in the life cycle AFTER viral entry but BEFORE reverse transcription
List 2 TRIM5 things against retroviruses
1) destroys viral cell
2) activates innate immune response (acts as a pattern recognition receptor)
a potent antiviral factor
information suggests the presence of at least one paleovirus that was in genetic conflict with TRIM5 in the 4-5 million years in the human lineage since the human-chimpanzee divergence.
no information about when each of these three changes became fixed in the population—this could have occurred in
rapid succession or slowly over 4-5 million years.
8 protein coding changes have occurred since the split form chimpanzees, suggesting ...
multiple selection events with retroviruses in chimpanzees
the trim5 gene targets and destroys _____
Original data shows that the antiviral gene TRIM5 restricted HIV-1 better at points in evolution ________ than the chimp-human common ancestor than it does after that.
the single largest determinant of loss of resistance to HIV-1, was fixed before the chimp-human common ancestor
R332 amino acid
R332 mutation occurred after gorilla and before ______
What is so weird about the 1918 flu?
it had high death rate among healthy adults aged 15-34.
caused 675,000 deaths in US
the _____ lowered life expectancy by 10 years
Viral RNA from the 1918 flu was recovered from an _______ buried in permafrost
_____ has allowed for the generation of recombinant viruses containing 1918 hemagluttin (HA)
plasmid based reverse genetics
why was the 1918 flu so deadly?
it was able to replicate in the absence of trypsin
it was not restricted to the lungs like other flu's were
the enzyme ______ is required to alter the replicated virus to allow it to enter other cells that are only found in the lungs
why are most flu viruses restricted to the respiratory tract?
that is the only location where the protease that cleaves HA is produced
the HA protein of the A5 and A7 flu strains can be cleaved by proteases that are produced in many different tissues
--> can replicate in many organs of the bird
--> might explain why 1918 flu is so deadly
the ______ killed about 30-60% of the population, 75-150,000 million
black death (europe 1300s)
What was the 1300s theory of the black death?
planetary alignment caused a pestilence in the air
____ spread Y. Pestis
______ discovered Y. Pestis, the bacteria responsible fo the black death
Yersinia Pestis =
Y. Pestis, black death
list 3 things that can affect the immune system
Evolutionary arms race
Immune system can be affected by stress, nutrition, environment
A balance between susceptibility and protection from a certain pathogen
what was the black death so deadly??
Y. pestis could suppress and avoid normal immune system responses such as phagocytosis and antibody production
EVADES THE IMMUNE SYSTEM
a potent initiator of the mammalian innate immune system
down regulates the expression of flagellar systems in a temperature-dependent manner, and none of the known Y. pestis strains express flagellin due to a frameshift mutation in the flhD regulatory gene
a mutation in the ____ regulatory gene is responsible for immune evasion of the black death
the _____ gene was totally functional 3000 years ago, but a mutation in the gene began to accumulate 2000 years ago
allowing for the BLACK DEATH
bubonic plague =
debate has prompted researchers to explore the possibility of genetic susceptibility, where low-genetic variation in HLA genes and immunologically naïve populations
are linked to the exacerbated pathogen-associated mortality rates
low genetic variation in native americans played big part in their inability to overcome european borne pathogens
The best way to examine if this local adaptation occurred in the ancient Americas is to use ________
____ suffered massive population declines in the 1800s due to smallpox epidemics
_____ is a efficient strategy to selectively sequence the coding regions of the genome as a cheaper but still effective alternative to whole genome sequencing
short, functionally important sequences of DNA which represent the regions in genes that are translated into protein and the untranslated region flanking them
there are about 180,000 _____ in the human genome, constituting 1% of human genome
the protein coding regions of the genome constitute about ______% of the disease-causing mutations
The modern Native Americans, in green, are drifting towards Europeans, suggesting admixture.
In this maximum likelihood tree, the Ancients appear ancestral to the living population after European admixture is accounted for.
the most extreme signal in the ancient population came from the ______, which is crucial for the immune system
MHC class II molecule
allows the immune system to identity infectious pathogens and eliminate them
major histocompatibility complex (MHC)
the main selection force that drives and maintains eh extraordinary diversity of the MHC
functions by detecting particles, antigens, from pathogens and alerting the adaptive immune system to launch a targeted response to that specific pathogen.
there was a 70% drop in the HLA alleles between the ancient and modern populations. what could have caused this?
european admixture, indigenous HLA alleles could have been replaced by european ones
HLA gene scenarios
1) positive - positive selection continues past european contact
2) neutral - frequency drop can be explained by bottleneck, where ancient alleles simply didn't make it through
3) Negative - negative selection removed the alleles from the population due to some maladaptive consequence.
negative selection did generate matching frequencies, giving the inference that this was the best explanation for the drop in the modern population.
It seems that they first adapted to pathogens in the ancient environment through the HLA-DQ gene
this same gene was then negatively selected for after European contact
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