Introduction and Evolution of HIV Flashcards
Understanding the processes of evolution is highly relevant to?
human health
It is concerned with explaining and understanding the diversity of living things and their characteristics.
Evolutionary biology
It extends and amplifies
the explanation of biological phenomena.
Evolutionary biology
Evolutionary biology extends and amplifies
the explanation of biological phenomena complementing?
proximate causes and ultimate causes
immediate, mechanical causes
proximate causes
their historical causes, especially the action of natural selection
ultimate causes
Nothing in Biology Make Sense except in the light of Evolution by
Theodosius Dobzhansky (1900-1975)
- The increase in fitness over time due to natural selection, or adaptation
- The accumulation of mutations, which alter fitness over time
- The change in allele frequencies (or the heritable expression of
those alleles) in a population across generations - The progression into more complex forms of life
Evolution
Evolution is the increase in fitness over time due to ____ _____ or _____ _____
natural selection or adaptation
Evolution is the accumulation of ______, which alter fitness over time
mutations
Evolution is the change in ____ ______ in a population across generations
allele frequencies
the heritable expression of those allele
allele frequencies
Evolution is the progression into more
complex forms of life
Evolution is change in ______ of genetically different individuals at each generation
proportions
I leads to an average change in characteristics of populations over time
change in allele frequencies or the heritable change in the expression of those alleles
change in allele frequencies
(genetic composition
heritable change in the expression of those alleles
epigenetic inheritance
Evolution acts by removing individuals from the population or by allowing some
to leave more offspring
A group of interbreeding
individuals and their offspring (in the case of sexual species)
population
The change in allele frequencies (or the heritable expression of those alleles) in a population across
generations.
evolution
Even if allele frequencies in a population remain the
same across generations, a population is evolving if it goes out of the _____
Hardy-Weinberg Equilibrium
It show follow HW expectations, given the allele frequencies
genotype frequencies
How does evolution occur?
through 5 major mechanisms: genetic drift, mutation, heritable epigenetic modification, migration, and natural selection
Totally random changes in allele frequency from generation to generation
Genetic Drift
Changes in the genetic code, such as error in DNA replication, gene deletions or duplications, etc.
Mutation
heritable changes that are not due to changes in DNA sequence itself, but the expression of the DNA, such as changes in DNA methylation and histone modifications, etc.»_space; changes “epi-alleles” not the genetic code (actual alleles
Epigenetic inheritance
Alleles moving from one population to another
Gene flow (Migration)
When some alleles favored over others due to an increase in fitness (not random); acts on genetic variation in the population
Natural Selection
How does evolution occur?
Natural Selection
What are the sources of genetic variation?
- mutation
- epigenetic inheritance
- genetic drift
It generates genetic variation
mutation
It changes expression of genes
Epigenetic inheritance
It reduces genetic variation
Genetic drift
It acts on genetic or epigenetic variation in a population
Natural Selection
Without it, natural selection cannot occur
genetic or epigenetic variation
Evolutionary concepts permeate all aspects of biology
- Biotechnology
- Agriculture
- Medicine
- Conservation
Many of our food is a product of intense
artificial selection or human-induced evolution
It is the fastest evolving organism on Earth
HIV
It infects macrophages and T-cells
HIV
It is among the deadliest epidemics in human history
AIDS
WHO estimates in 2019 that _____ have died and ___ have been infected, and ___ people currently living with AIDS
- 32.7 million
- 75.7 million
- 38 million
What are the body fluids that transmit HIV?
- blood
- semen(cum)
- rectal fluids
- pre-seminal fluid
- breast milk
- vaginal fluids
Only certain ____ ____ from a person who has HIV can transmit HIV
body fluid
This fluid must ______ from a needle or syringe for transmission to occur
- come in contact with a mucous membrane or damaged tissue
- be directly injected into the bloodstream
Mucous membranes are found inside the
- rectum
- vagina
- penis
- mouth
Mode of transmission HIGH RISK
- sexual intercourse
- injection drug use
Mode of transmision LITTLE NO RISK
- oral sex, biting, spitting
- food contamination
- deep, open-mouth kissing
- touching
- tattoos, body piercing
- medical care
Likely mode of transmission in year 2002 of Cambodia, Honduras, Russia, Indonesia, and Kenya (1998)
- injection drug use
- sex work
- heterosexual sex with a partner at high-risk
- male-male sex
- casual heterosexual sex
Likely mode of transmission in US (2006), Canada (2005), and UK (2007)
- male-male sex
- MMS & IDU
- Injection drug use (IDU)
- heterosexual sex
- Retrovirus with two single strand RNAgenomes
- Uses the enzyme reverse transcriptase to replicate RNA → DNA
- Has an integrase to
incorporate its genome to the host genome - Attacks host immune
system: infects macrophages and helper Tcells
Human Immunodeficiency virus or HIV
HIV is a ___ with two single strand RNA genomes
Retrovirus
HIV uses the enzyme ____ ____ to replicate DNA
reverse transcriptase
HIV has an ___ to incorporate its genome to the host genome
integrase
HIV attack ____ and infects ____
- attack host immune cells
- infects macrophages and helper T cells
It capture the virus and present bits of its proteins to naive helper T cells
Dendritic cells
This cells divide to produce effector helper T cells
Naive cells
It stimulates B cells displaying the same bots of viral protein to mature into plasma cells, which make antibodies that bind and in some cases inactive the virus
Effector helper T cells
It also activate killer T cells, which destroy host cells infected with the virus
Effector helper T cells
It destroy host cells infected with the virus
killer T cells
Mots of it are are short, but a few become long-lived memory helper T cells
effector T cells
HIV has the ____ _____ ___ of any virus or organism observed to date
fastest mutation rate
It evolves more rapidly than humans and more quickly than the ability of humans to produce new drugs
HIV
These are unlikely to work on all strains of the virus and unlikely to work on a given strain in the long run
AIDS vaccines
HOW might HIV evolve?
Drugs impose selection on HIV —-> transmission rate imposes selection on HIV ——-> host immune system also imposes selection
evolution of drug resistance
Drugs impose selection on HIV
evolution of virulence
transmission rate imposes selection on HIV
it also imposes selection on HIV
host immune system
It is a thymidine mimic which stops reverse transcription and impedes viral replication
Azidothymidine (AZT)
Example of an HIV drug
AZT
Why does AZT work initially but fail in the long run?
fat mutation rate
natural selection
Lots of mutations arise, including in the reverse transcriptase gene of HIV—->
Fast Mutation rate —–> genetic variation
It favors reverse transcriptase enzyme mutant that can recognize AZT and not use it
Natural selection
an enzyme thatnis
slow, but the virus is now resistant to AZT
careful reverse transcriptase enzyme
The careful reverse transcriptase enzyme is
slow, but the virus is now resistant to AZT
evolutionary tradeoff between fast & sloppy
vs. slow & careful enzyme
It favors mutants that are resistant to AZT
Natural selection
Mutations in the viral reverse transcriptase gene of HIV arises
Fast mutation rate
Favors reverse transcriptase enzyme that can recognize AZT and not use it
Natural Selection
These mutations slow down the virus (as it becomes more careful), but makes the virus resistant to AZT
tradeoff between speed vs. accuracy of reverse
transcription
Why does fast & sloppy are favored?
because fast replicating mutants would outgrow the slower
What would happen when AZT therapy stops?
Back mutations that restore the amino acid sequence to the original state are then favored by selection so that
reverse transcription could speed up again
Evolutionary tradeoff between fast viral population growth versus keeping the host alive
Need to keep host alive long enough to get passed on to the next host
can grow fast and jump to the next host; ok if host dies; the genetic strain that grows faster will win
High transmission rate: High virulence
More virulent strains would die with the host and get selected out; less virulent strain that does not kill the host will win
Low transmission rate; low virulence
will select for high virulence
High Transmission rate
If the virus is likely to move to a new host, the faster growing (and more virulent) strain is likely to overtake
the slower strains and “win”
High Transmission rate
Kill the host since the chance of jumping to a new host is high
High transmission rate
It favors the more virulent strain
Natural selection
Will select for low virulence
Low transmission rate
If the virus is not likely to move to a new host the slower growing (and less virulent) strain is likely to
“win
Low transmission rate
since the chances of jumping to a new host is low. If the virus kills the host, it will kill
itself
It’s not ok to kill the host
will favor the less virulent strain
Natural selection
How to combat HIV
- must lower transmission rate of HIV so that less fatal strains evolve
- must understand evolutionary properties of a disease
Must understand evolutionary properties of a disease
- evolutionary history
- mutation rate
- selective forces
- evolutionary tradeoffs
evolution in response to AZT
slow and accurate vs fast and sloppy replication
Evolution in response to transmission rate
slow growing & less virulent (keep host alive_ vs fast growing & more virulent
