Cycle 1: Evolution is Happening

Question 1

What are some key characteristics of viruses?

Answer 1

Viruses do not belong on the tree of life! They are able to evolve, as we will see in the rest of this lecture, so why isn’t it considered living? Life is defined as having an independent metabolism…viruses do not fit that definition…they have no reproductive mechanisms and they are obligate parasite.
Viruses are obligate parasites which means that they are unable to reproduce on their own- they must rely on infecting and integrating itself into some host cell in order to replicate.

Question 2

What is a retrovirus?

Answer 2

HIV is a virus, it is single stranded and considered a retrovirus. So what is a retrovirus?
A retrovirus is a type of virus which uses RNA as its genetic material. Once a retrovirus infects a cell, it uses an enzyme called reverse transcriptase to convert its own RNA into DNA- this way, with its newly made viral DNA, it can be inserted into the host cell’s DNA. Now that the viral DNA is in the host cell’s DNA, viral DNA is also able to be transcribed and translated to make new virions.

Question 3

What are some differences between a virus and a cell?

Answer 3

Structure of virus: DNA or RNA in capsid core
Structure of cell: cell membrane, cytoplasm, eukaryotes contain nucleus/organelles

Reproduction in virus: only within a host cell
Reproduction in cell: independent cell division

Genetic code in virus: DNA or RNA
Genetic code in cell: DNA

Growth and development in virus: no
Growth and development in cell: yes, in multicellular organisms

Obtain and use Energy in virus: no
Obtain and use Energy in cell: Yes

Response to environment in virus: no
Response to environment in cell: yes

Change over time in virus: yes
Change over time in cell: yes

Question 4

The origins of HIV

Answer 4

HIV is an example of zoonotic diseases and spillover events
- Disease that was originally present in non-human animals and transferred to humans
- 75% of new infectious diseases have spilled over from nonhumans
- Spillovers are more likely between closely related species
- Usually the spillover is more harmful in the new host than in the original host species ( It may be less harmful in the original host species because it has resided in the host species for a long time)
- SIV was originally the predecessor of HIV
Has long history of infecting nonhuman primates
- SIVs have spilled over to humans several times

Question 5

Why is it so hard to eradicate viruses?

Answer 5

Viruses have very little of their own machinery
As obligate parasites, they rely on the host cell for their reproduction…
This means targeting a part of the virus’ cycle could also harm the host cell it hijacked, and cause even more damage to the host organism

For instance, if we targeted the assembly phase of a new virus capsid, this would be very difficult to do because the virus is using so many components from the host cell in order to do this, so we might actually end up harming the host cell instead

Question 6

AZT HIV treatment

Answer 6

Antiviral drugs are often harder to design or discover than antibiotics, and usually have much more serious side effects than antibiotics do.

A key player here for HIV is its reverse transcriptase- it is what helps turn its own single stranded RNA into a double stranded DNA that will then be able to be inserted in the host cell’s DNA. And something interesting is that humans do not have its own reverse transcriptase. This reverse transcriptase is unique to the HIV, so lets target that when developing antiviral drugs!

So let’s talk about reverse transcriptase a bit more. A characteristic of reverse transcriptase is the fact that it is not perfect and makes mistakes; there is no proofreading enzymes … it will incorrectly base pair and just move on with its life and not double check its mistake nor will it fix it. It will wrongly base pair and thus give rise to mutations… The fact that this enzyme, reverse transcriptase, is prone to error when going from RNA to DNA, thus causing a high mutation rate, is something important to keep in mind when considered vaccine development and long term effective antiviral drugs.

But let’s consider a drug used to treat HIV- AZT.
AZT is a nucleoside analog- which means that it looks similar to thymidine, but not identical. Instead of having an OH group on the 3’, it has N3. This change in structure is what makes AZT effective in HIV treatment.
When the reverse transcriptase is doing its job and adding on nucleotides to the DNA chain, and it needs to pick up a thymidine … but if the AZT analog is there, the reverse transcriptase will pick that up instead. But when the AZT is added instead of the thymidine, it will block DNA elongation. The N3 which is sitting on the 3’ of the AZT prevents further nucleotides from being added. This stops the action of reverse transcriptase. Now this viral DNA is not complete!

Question 7

Is AZT a long term antiviral treatment?

Answer 7

• The reality was that once we exposed HIV to this drug, the virus managed to become resistant… How??
• ONLY 2 nucleotide changes in reverse transcriptase … now there is a proofreading function (knows the difference b/w AZT and thymidine)
• Antiviral drug effectiveness decreases over time

Yay! Now that there is the AZT treatment for HIV… that is good! BUT…

The reality was that once we exposed HIV to this drug, the virus managed to become resistant. So even if the drug was introduced into the host, the reverse transcriptase was not susceptible to it anymore. Why??

It just takes two nucleotide changes to enable the reverse transcriptase to have a proofreading function. With this new proofreading function, reverse transcriptase can now tell when it has picked up an AZT nucleotide when it was supposed to pick up a thymidine.

Question 8

How did HIV evolve resistance to AZT?

Answer 8

So now that we know there has been resistance conferred onto the HIV population, we want to know how this happened. How did the HIV evolve resistance to AZT?

Let’s map it out. As reverse transcriptase is copying the HIV genome, from RNA to DNA, it will make mistakes. Remember that reverse transcriptase is not so good at its job and it does tend to make errors. A mistake will lead to a mutation in the genome. As more rounds of replication occur, more mutations are accumulated. Eventually, after several rounds of replication, there are variants in the HIV population. Some are still susceptible to the AZT antiviral treatment, while some of the HIV population is resistance and is thus able to reproduce in the presence of AZT. This subset within the HIV population is drug-resistant.

It is important to note that mutations are RANDOM. They occur randomly along the genome due to the fact that reverse transcriptase is not so good at its job and will incorrectly base pair.

• RT makes mistakes in copying HIV genome (from RNA to DNA), resulting in a mutation
  Remember … reverse transcriptase is not so good at its job and DOES make mistakes
• The mutation in the next generation of RT created MIGHT confer resistance to AZT or it MIGHT NOT
  Where these mutations occur in the genome is completely RANDOM
• If there are AZT-resistant mutants, they would accumulate in the population as more rounds of replication and AZT treatment occur
• Over time, the genetic makeup of the virus population changes…
  Resistant viruses are favoured by natural selection and make up a greater portion of the total population than before

Question 9

What is a drug cocktail therapy?

Answer 9

Using multiple drugs as therapy
- Dilutes possibility of total resistance

• Key takeaway is that effective viral therapies target MANY parts of infection
• Very unlikely for a strain to develop resistance to all (developing resistance to even one is unlikely enough!)

Question 10

The Vaccine Effort VS Evolution

Answer 10

• Viruses divide very fast
  → Mutations accumulate very fast
  → Viruses change very fast
  → Faster than we can catch up!
  Evolution:
  happens over generations, and is driven by mutation.

Viruses divide fast → replicate their genomes very often → potential for mutations
Viruses mutate/evolve very fast as a result
Key takeaway is that evolution happens over generations, and you need mutations to introduce change!

Question 11

Features of scientific theories.

Answer 11

A scientific theory must be:
Testable: can be revised, and experiments can be run on it
Falsifiable: if contradicting evidence appears, can the “theory” be claimed “false?”

Falsifiability is tested by presenting a hypothetical negative/contradicting evidence
If you can perpetually gaslight yourself or defend the theory despite contradicting evidence, it is not falsifiable (similar to beliefs)

Evolution is a scientific theory that has been tested before, and is able to be falsified (but we haven’t found anything that goes against the theory)

Question 12

The theory of Evolution 1.

Answer 12

Evolution states that all life shares a common ancestry, and lineages diverges to form new species == a complex way of saying all life is related
This was suggested true by the existence of LUCA, the life form that birthed all life on earth

What LUCA was is not important. LUCA’s existence simply helps us understand the first aspect of the theory of evolution.

New species constantly forming from previous ones
Thus: all organisms are related.

Question 13

The Theory of Evolution 2.

Answer 13

The second aspect is that life changes over time, mostly through a process called natural selection.

Natural selection is one such way life changes or evolves — there are many other ways like genetic drift, gene flow, migration… (these appear in Cycles 6-10)
The through definition of evolution is that allele frequencies change in a population

Natural selection is a process where in a population (all members of one particular species), variation arises by mutation.
There are specific reasons or “pressures” that may favour one such variant over the other.
These variants that are favoured or “more fit to outlive their competitors” will live longer and make more offspring.
The next generation of that population will consist of more offsprings from these “favoured variants,” rather than unfavoured.

Here is a hypothetical example:
The first prerequisite for evolution is variation. Within the western Canadian goose population, one trait in which we may see variation is height; there will be some small geese, and some small geese.
This variation becomes evolutionarily significant when there is some sort of selective pressure. Imagine that Western realizes it has a geese problem, and so the university sets up a goose fence around the campus that only the tall geese are able to cross. In this case, the fence would be considered a selective pressure. Seeing that the smaller geese do not have access to all of the nutritious grass on campus, fewer will survive to reproduce; i.e., there is non-random survival.
Lastly, in order to undergo evolution, traits must be heritable, or capable of being passed onto offspring. As a result of heritability, we expect geese to be taller in the next generation (as they inherit a genome that is conducive to becoming tall from their tall parents). Tallness, now a beneficial trait, is deemed an adaptation.
But how does new variation come about in the first place? The answer is mutation (or a change to the genotype). You will learn more about the mechanisms of mutation—both endogenous and exogenous—in later lectures.

Question 14

What are some core aspects of Darwin’s and Lamarcks views?

Answer 14

External factors changing species is the core aspect of Darwin’s ideas. Darwin also states all species are related.

Lamarck proposed an individual-driven evolution, and this is the most relevant statement. Organisms can simply decide to change over their lifespan, and these purposeful changes drive species-level change.

Question 15

The Theory of Evolution 3.

Answer 15

Natural selection is one such REASON evolution happens — it’s not evolution itself!
- Natural Selection
- Gene Flow
- Genetic Drift
- Mutation (without selection)
- Sexual Selection
EVOLUTION

Question 16

What are the core principles of the theory?

Answer 16

1) Organisms change/diverge over long periods of time,
2) All organisms are related, however distant,
3) Evolution changes populations, not individuals,
4) Natural selection is one agent driving evolution.

Question 17

What are some misconceptions about evolution?

Answer 17

1) In our modern world, evolution is occurring at a significantly lower rate than it did millions of years ago.

Evolution is certainly ongoing! All antecedent conditions for evolution (variation, non-random survival and heritability) are still present in today’s organisms. Even humans are still evolving; this will be explored in greater detail in further lectures.

2) Individuals with a greater fitness are almost always stronger, faster, and larger, seeing that these traits are conducive to reproductive success.

Fitness is simply defined as reproductive success. It has nothing to do with the word ‘fitness’ in its everyday use. In the evolutionary sense, an animal that has 5 offspring is more ‘fit’ than an animal that has 4 offspring, even if the first animal is smaller, uglier, less intelligent, etc.

3) Chimpanzees evolved into humans

Chimpanzees did not evolve into humans; rather, chimpanzees and humans share a common ancestor from which both the present-day humans and the present-day chimpanzees evolved.

4) An individual organism cannot evolve over the course of its lifetime.

Evolution is variational, not transformational. Usually, traits that an organism acquires over the course of its lifespan are not passed onto the next generation. The one potential exception to this is epigenetic changes, but don’t worry about this yet.

5) A bacterium plated in an antibiotic medium is equally as likely to develop a mutation that confers antibiotic resistance than bacteria plated on nutrient agar.

Remember that MUTATION IS RANDOM, therefore all bacterium plated in an antibiotic medium is EQUALLy likely to develop the mutation

6) Evolution does not result in organisms that are perfectly suited to their environment.

Question 18

Evidence for Evolution (“Macro” Scale)

Answer 18

Biogeography → similar species in different places, but a few changes have occured
∴ Common ancestor moved to a new location → new selective pressures → undergo changes

Comparative morphology → different species have similar morphological characteristics (Homologous traits)

∴ Common ancestor had this particular morphological characteristic (limb structure), which was passed down to all three species

When species share similar characteristics due to common ancestry, these are deemed homologous traits (this phenomenon is known as homology).

Comparative morphology → different species have similar morphological characteristics (Vestigial structures)

∴ Ancestor had a use for the pelvis, and even though it is no longer needed, there has been no selective pressure against this structure

A vestigial structure can be seen as the remnants of a species evolutionary past. It is a structure that was necessary in one of its ancestors, but no longer serves any use.
A good example is the remains of a pelvis in whales, which would have served a purpose for the whale’s land-dwelling ancestor.
The human appendix is also sometimes considered a vestigial structure, but it may in fact serve a purpose in the microbiome.

Similarities between species do not always indicate recent common ancestry. Thus, it is integral to ensure that similarities which may be suggestive of homology are not simply superficial similarities.
Consider the wings of a bat and a bird. One may assume that the wing structure—along with the ability to fly—evolved in a common ancestor and was then passed on to both the bat and the bird. But this is not the case! Bats and birds did of course share a common ancestor at one point in time (as did every single living organism on earth), but this organism did not have wings and could not fly. Bats and birds actually independently evolved wings after diverging from a common ancestor.
Note, however, that as in the previous diagram, the limb structure (i.e., the bones themselves, not the wings) are in fact homologous. The common ancestor of bats and birds shared this common bone structure (with a radius, humerus, etc.) but it could not fly.

Geology → Earth has been around for a very long time!
∴ Just like geological change, evolutionary change is gradual (with some exceptions) and has had a lot of time to occur

Fossils → Shows that life on Earth today is different than it was in the past; allows comparisons

Fossils → Shows that life on Earth today is different than it was in the past; allows comparisons

Evolution has actually stolen several of its foundational ideas from geology.
The discovery that the Earth has been changing for billions of years sparked the idea that organisms could do the same.