So, I've demonstrated both common and uncommon evolutionary changes on the nano scale, during
a single infection in a single patient.
What about the microevolutionary changes?
Here I'm talking about the variation in HIV since it first jumped to humans some time
at the beginning of the previous century, between 1900 and 1950.
I should start by pointing out that when we say HIV, we usually mean HIV type 1.
There's also HIV type 2, which likely evolved independently in a completely different jump
from a different animal source.
HIV-1 appears to have jumped from chimpanzees to humans, and HIV-2 from sooty mangabeys.
HIV-2, for the most part, is confined to Africa.
It has a very similar, but not identical, gene structure and life cycle.
Among HIV-1, there is a division called "Groups".
Group M, which stands for Major, represents 90% of all HIV infections globally.
Among Group M, we subdivide further into subtypes.
If you are in Southern Africa, China or India, the dominant subtype is designated subtype
C. In North America, almost all cases are going to be subtype B. Subtype J is emerging
as dominant in the Carribean, and D in Russia.
Each of these different subtypes varies ever so slightly from other subtypes.
Given enough time, these differences are increasing.
Recent reports suggest that subtype D in the infected population of Uganda has an accelerated
disease progression.
It is a more virulent virus that is also spreading more quickly and causing worse disease.
Subtype B, accounting for almost all disease in North America, shows higher efficiency
transmission by homosexual sex than the other diverse forms, which may explain the initial
epidemiology of the disease in the US.
This is how evolution can tell us the likely future course of the global HIV epidemic.
By understanding that HIV is evolving in different parts of the world, we'll be able to adjust
the sensitivity levels of diagnostics to prevent the most disease and save the most lives.
There's another set of changes we should address on the microevolutionary phase: Drug resistance.
This has already been discussed so many places, but our current therapeutic strategies are
based on an understanding of how natural selection acts on an evolving population.
In the case of HIV, we intially only had a single drug that acted on the ability of the
virus to copy itself.
Why that drug, and not something that acted on the entry of virus into cells?
Because we had already determined that the entry process was highly mutable and evolved
very quickly.
The viral replication mechanism, reverse transcriptase, was something that we could determine was
highly constrained by evolution.
What made it work was a specific shape of the enzyme.
Any alterations made that enzyme inactive.
On the other hand, the surface envelope molecules we talked about earlier continued to work,
at least weakly, with major alterations.
It's much harder for the virus to evolve a resistance to drugs targeting replication
than it does for them to evolve new mechanisms of entry.
We also mapped the variations in the viral proteases, which were also highly conserved
through evolution.
That led to the development of protease inhibitors, drugs which targeted these highly conserved
enzymes.
Any one of these single drugs could still be bypassed by evolutionary change very quickly.
HIV has a remarkable ability to innovate new pathways, which makes sense because it undergoes
both extreme diversity and extreme selection.
By combining three drugs or even four into a single cocktail, we set a higher hurdle
for evolution.
It must now innovate four separate times to be successful.
Sadly, even this innovative strategy doesn't work forever.
Eventually, a virus emerges which is resistant to all of the drugs, and the patient gets
no further relief.
Now we're back to the funeral scenario.
In a study of female bar and hotel workers in Northern Tanzania, 7% of HIV samples showed
a primary resistance to the AZT class of drugs, RT inhibitors, and 7% had resistance to all
the protease inhibitors.
Statistically, we would then expect about a half a percent to be completely resistant
to the triple cocktail.
Lastly, let's look at the macro scale of evolution of lentiviruses.
HIV is in this viral family, formally called the Lentiviridae, which includes these closely
related viruses.
FIV, or feline immundeficiency virus, which causes immunocompromise in cats, and which
is found in almost 90% of healthy wild lions in Africa but is almost invariably fatal in
domestic cats.
There's also the bovine immunodeficiency virus, found in cows.
The Puma immunodeficiency virus found in New World cats, the more distantly related CAEV
found in goats, the EIAV found in horses, and the Visna virus found in sheep.
All of them cause some form of immunopathology, or disease through disorders of the immune
system.
All of them have the same basic gene structure and life cycle.
We've already mentioned the likely origin of HIV from the simian immunodeficiency virus,
another important Lentivirus, possibly having jumped from other primates or monkeys to humans
multiple times.
The level of macroevolution in these viruses tells us how they are related.
It gives scientists a way to find the origin of HIV.
This was my work, reconstructing the phylogeny of lentiviruses.
It's one of the big questions in all of virology.
Where do viruses come from?
In the case of HIV-1, we have three samples to compare.
One is taken from a wild chimp colony in Western Africa.
The other is an old clinical sample taken from a 28 year old woman living in Kinshasa
in 1960, and the oldest HIV sample to date, collected in 1959 in the vicinity of Kinshasa.
The three are not quite identical.
Of the portion they were able to sequence, the difference between the two human samples
collected one year apart is about 12%, and differed from the chimp sample by about 30%
in that same region.
From these comparisons, and knowing what we do today about viral evolution, that puts
a rather precise date of origin for HIV-1 at 1908, with a 95% probability the the origin
was between 1884 and 1924.
So, evolution as a tool, as a model and a framework means that we understand this pathogen
better.
We know where it came from, chimpanzee SIV, we know when it jumped to humans.
More than that, though, a comparison of the genomes of all the lentiviruses has led us
to a major breakthrough.
One of the key differences between SIV and HIV is the type of accessory gene products
and particularly one called vpr, or viral protein R.
The same sequence exists in SIV and FIV and EIAV, but it's far more mutable.
We find more variation in it.
In HIV, it's highly conserved.
That led scientists to investigate it more closely.
To early examination, it was a minor, unimportant viral protein that was apparently too small
to do much, but the lack of sequence diversity and the alignment to viral genes in SIV and
HIV-2 led them to discover the truth about this protein: It has at least four distinctive
functions that make HIV so deadly.
It does things like stopping the growth of immune cells, transporting the virus into
the nucleus of the cell, and it regulates viral expression.
The ancestor of HIV lacks some of these functions, so it's likely the product of evolution.
It's an amazing target for gene therapies, and it's an understanding of how the lentiviruses
have evolved in response to their hosts that led us to identify that vpr even mattered
or played a role in the cell.
We've taken a look at three different levels at which evolution operates on HIV.
What I hope I can call your attention to in each of these levels is that evolution is
not being asserted.
Evolution is the model, the tool that scientists and medical researchers have used to make
major strides in treating a deadly disease that tears apart families and kills the young
and innocent.
You asked for proof that evolution is a fact, as though that were something that modern
biologists were really apprehensive about.
The proof of evolution is in the fact that is a predictive model of practical utility.
It's like the theories of physics to an engineer.
The idea of contesting something that can be used to hit an asteroid millions of miles
away with a small probe launched from a rocket never enters their mind.
They work with the theories of physics every day.
Likewise, evolution has been described as the unifying theory of biology.
"Nothing in biology makes sense except in the light of evolution", as Dobzhansky so
famously said.
That's the reality, OnceForgivenNowFree.
Now I have little or no hope of changing the mind of even a single creationist, yourself
included.
I don't think this is something you are prepared to be logical or rational about.
You've internalized your creationism and it would be too painful for you to question this
core belief, but this gave me an opportunity to tell you WHY I oppose your attempts to
inject religious dogma into science education.
It's because every day molecular biologists show up to their labs.
They work for little pay on problems that reduce suffering and pain, make life on Earth
a little brighter.
They use evolution to do that.
I know you think you're doing a good thing, trying to get your religious beliefs into
that lab by way of the educational system or public funding choices, but I'm here to
tell you that you're only going to replace a workable model of genetic change with something
that doesn't answer any questions except how much you are willing to let others suffer
for your religious beliefs.
I think that's an ugly and an evil thing.
Thanks for watching.