Intro to Evolution lecture 1

1. Lecture 1
HIV as a case study for
contemporary evolution

2. Approach
Each week: core set of topics
+
Examples of its application and evidence

3. Evolution
What is it and why should you care?
Evolution is key to understanding many biological processes:
- Historical: How do species arise?
- Contemporary: Consequence of biodiversity loss
- Ecological processes: Host-parasite interactions
- Human health: Evolution of drug resistance, cross-
species disease transmission
- And much more.

4. Lecture 1
The case for evolutionary
thinking: HIV (and a little DNA review)

5. Outline today
1. DNA - what and where
2. HIV exemplifies many aspects of evolution

6. Evolution and DNA
• Not all evolutionary studies use DNA
• Phenotype is also important
• Phenotype = Observed traits in an individual

7. Evolution and DNA
• Not all evolutionary studies use DNA
• Phenotype is also important
• Phenotype = Observed traits
• But we need to understand how DNA contributes
• Genotype = the genes the individual has

8. Review: Remember DNA?
Important to understand:
• What is DNA?
• Where is DNA?
• How is DNA replicated?
• How do we get new combinations?

9. Review: DNA
You probably know a cartoon version of DNA
You know it’s in
the nucleus

10. Review: DNA
• A complex molecule.
Mostly made of:
• Carbon, Hydrogen,
Oxygen, Nitrogen, and
Phosphorus (CHONP)
Credit: Zephyris

11. A C T G
• Purines - Double ring. A and G
• Pyrimidines- Single ring. C and T (and U)
This will be important later when we talk
about types of mutations.

12. Only one way to pair them:
Sug
ar
Sug
ar Sug
ar
A denine( A ) T h ymine( T ) G uanine( G ) C yt
os
ine( C )
Sug
ar
/ 2 0 1 7 Pea
r
s
onEdu
c
a
t
ion
, In
c
.
Two hydrogen bonds Three hydrogen bonds

13. Review: DNA
• Often simplified by just
reading one strand:
A C T A G
A C T A G
A C T A G
A C T A G
A C C A T
A C C A G
A C T A G
A
C
T
A
G
T
G
A
T
C
5 ′ 3 ′
3 ′ 5 ′
/ 2 0 1 7 Pea
r
s
onEdu
c
a
t
ion
, In
c
.

14. Molecular sequence data
Here, each row is the DNA
sequence found in one individual
individual 1
individual 2
individual 3
individual 4
individual 5
individual 6
individual 7
A C T A G
A C T A G
A C T A G
A C T A G
A C C A T
A C C A G
A C T A G
Mutations

15. Where is DNA?
It’s in the nucleus!
Animal cell
Nucleus with nuclear DNA
Plant cell

16. Some organelles have DNA too
• Mitochondria - in both plants and animal cells
SEM image
(the dots are ribosomes)

17. Some organelles have DNA too
• Chloroplast - photosynthetic
material in plant cells

18. Organelles with DNA?
These originate from
ancient
endosymbiosis of
free living bacteria
Eng
ul
f
ingofox
yg
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ingnonph ot
os
ynt
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ic
prokaryot
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h
bec
omesamit
oc
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A nc
es
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orofeukaryot
icc
el
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s( h os
tc
el
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)
M it
oc
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C h l
oropl
as
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A tl
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Eng
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ph ot
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prokaryot
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M it
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N onph ot
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eukaryot
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Ph ot
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iceukaryot
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19. Why is this important?
• Mitochondria and chloroplasts
both have many copies in each
cell cytoplasm
• Only maternally inherited
• Different replication machinery,
so different mutation rates
(more on this in lecture 4)

20. What’s the difference?
• What is the impact of different copy number,
inheritance, and mutation rate?
• Example from birds in Australia.
• Different patterns in nuclear and mitochondrial
genes.
• There can be a mismatch in the information in
these genes!
Morales et al (2017) Molecular Ecology 26(12):3241
mitochondrial nuclear
This is a citation. The originial
publication that made this picture
Eastern Yellow Robin

21. What’s the difference?
When we study evolution, we must remember what we are
measuring.
We might get different evidence from:
- a mitochondrial gene
- a nuclear gene
- counting the number of hairs on a leg

22. What’s the difference?
When we study evolution, we must remember what we are
measuring.
We might get different evidence from:
- a mitochondrial gene
- a nuclear gene
- counting the number of hairs on a leg
- bird songs

23. What’s the difference?
When we study evolution, we must remember what we are
measuring.
We might get different evidence from:
- a mitochondrial gene
- a nuclear gene
- counting the number of hairs on a leg
- bird songs
Genotypes

24. What’s the difference?
When we study evolution, we must remember what we are
measuring.
We might get different evidence from:
- a mitochondrial gene
- a nuclear gene
- counting the number of hairs on a leg
- bird songs
Phenotypes

25. Summary of DNA
• Complex molecule with two strands
• Composition can be summarized ACTG
• Different traits (i.e. genotypes and phenotypes)
---> with different evolutionary histories
Questions??

26. Outline today
1. DNA - what and where
2. HIV exemplifies many aspects of evolution

27. How HIV uses cells to replicate

28. 1. Mutation and selection
• Early HIV treatment: AZT
• Drug mimic “T” during replication
• Stops reverse transcription

29. AZT mimics Thymine (ATGC) and
stops reverse transcription

30. AZT stops working after a few years.
• Why?
• Have a closer look at the
RT (reverse transcriptase)
active site
• Resistant viruses had a
small change at this site
• This RT worked in the
presence of AZT
Here: mutation causing resistance (Chapter 5)

31. Did AZT cause mutations?
• No!
• The drug (AZT) selected for resistant mutants that were
already there and arose randomly
Here: mutation causing resistance (Chapter 5)

32. Did AZT cause mutations?
Before After
• Before drug treatment, no advantage to being resistant
• This is a fundamental idea in evolutionary biology

33. Did AZT cause mutations?
Before After treatment
Evolution within a single patient

34. Did AZT cause mutations?
Before After
Selection for resistant types
Future infections more likely to be
resistant

35. HIV is always evolving in patients
• Random mutations
accumulate
• This shows two
different genes from
HIV, collected from
one person
• Most mutations have
little-to-no effect
Zanini et al (2015) eLife 2015;4:e11282

36. Court case in Louisiana
• Relationships among HIV strains used to show source of HIV
infection
• A doctor injected his girlfriend with a syringe containing HIV
• She developed HIV
• He argued in court that she could have contracted it
elsewhere

37. Court case in Louisiana
• Relationship among HIV strains
in community (1 gene)
• The victims virus is nested
within the sequences from the
doctor’s patients
• This evidence led to a
conviction
(Metzker et al (2002) PNAS: 99(22)14292)

38. • We can construct phylogenies that go
back farther in time
• Show multiple origins of HIV from wild
primates
• But only 1 group responsible for most
of the epidemic (group M)
• More on phylogenetics in chapter 4
Higher level relationships

39. Summary
• Review:
• DNA structure
• Where do we find DNA
• Evidence for evolution: genotype and phenotype
• HIV virus exemplifies many aspects of evolution
• Early drugs selected for existing resistant genotypes
• Phylogenetics help resolve relationships:
• Between strains in people
• Among species, showing historical movements

40. Questions?
• Review:
• DNA structure
• Where do we find DNA
• Evidence for evolution: genotype and phenotype
• HIV virus exemplifies many aspects of evolution
• Early drugs selected for existing resistant genotypes
• Phylogenetics help resolve relationships:
• Between strains in people
• Among species, showing historical movements