1) Evolutionary genetics examines how genetic changes in populations lead to evolution over time through processes like mutation, genetic drift, and natural selection. 2) Early work in evolutionary genetics integrated Mendelian genetics with Darwin's theory of evolution through natural selection to form the modern synthesis of the early 20th century. 3) Neutral theory proposed that many genetic mutations are neutral or nearly neutral and do not significantly impact fitness, explaining much molecular evolution. 4) Phylogenetic trees reconstructed from genetic data provide evidence for relationships between species and models of molecular evolution. 5) Horizontal gene transfer and archaic human interbreeding have introduced genetic variation influencing traits like placental invasiveness and immunity.

1. Evolutionary Genetics
Human Genetics
http://slideshare.net/dangaston
daniel.gaston@dal.ca
March 7th, 2016Dr. Dan Gaston

2. "Nothing in Biology Makes Sense Except in the
Light of Evolution"
-- Theodosius Dobzhansky

3. Evolutionary Genetics
Genetics Evolution

4. Evolutionary Genetics
Population
Genetics
Evolution

5. Evolutionary Genetics: Darwinian Origins
Voyage of The Beagle: 1831-1836
Origin of Species: November 24th, 1859

6. Evolutionary Genetics: Mendel and Genetics
• Gregor Mendel's experiments:
1856-1865
• Mendel's rediscovery and early
modern genetics (de Vries,
Bateson, Morgan, Punnet): Early
1900’s

7. The Forces of Evolution
•Mutation
•Genetic Drift
•Selection

8. Mutation

9. Genetic Drift

10. Selection
• W = 1 – s
• W: Fitness
• s: Selection Coefficient
• s = 1 (Lethal)
• s = 0 (No difference in fitness)

11. Evolutionary Debates of the early-mid 20th
century
• Primarily differences in view and opinion on relative importance of
different forces:
• "The Mendelians": Geneticists who generally asserted the primacy
of mutation to greater or lesser degrees
• "The Naturalists": Field Biologists who generally asserted the
importance of natural selection

12. Evolutionary Genetics: Modern Synthesis
• The foundation of Evolutionary Genetics is the foundation of Population Genetics (1918-1939):
• RA Fisher
• JBS Haldane
• Sewall Wright
• The naturalists (1940s):
• Theodosius Dobzhansky
• EB Ford
• Ernst Mayr
• George Simpson
• Julian Huxley
"Natural selection is a mechanism for generating an exceedingly high degree of
improbability." - RA Fisher

13. Neutral and Nearly Neutral Theory of
Evolution
• Kimura (1968) and King and Jukes (1969) (Neutral Theory)
• Most genetic differences between organisms selectively neutral
• Synonymous mutations
• Molecular level dominated by neutral mutations and genetic drift
• Phenotypic level differences dominated by selection
• Expanded on By Tomoko Ohta and Kimura in 1973 (Nearly Neutral
Theory)
• In addition to neutral, beneficial, and deleterious mutations there are
also nearly neural mutations. Slightly deleterious and slightly
advantageous

14. Evidence for Near Neutrality
• Prediction: Fixation of Neutral sites will occur at the rate of mutation
(or nearly so for near neutrality)

15. Evidence for Near Neutrality
• Prediction: Fixation of Neutral sites will occur at the rate of mutation
(or nearly so for near neutrality)
• Evidence:
• Synonymous sites
• Introns
• Intergenic DNA
• Pseudogenes

16. Nearly Neutral Theory of Evolution

17. Neutral Evolution becomes the Null Hypothesis in Evolutionary
Biology. It is the default assumption in the absence of
evidence of selection

18. Mutation

19. Phylogenetic Trees and Models of Evolution

20. Phylogenetic Trees

21. Phylogenetic Trees

22. Phylogenetic Trees and Evolutionary Genetics:
Molecular Evolution
• Theoretical Framework in the 1960’s: Zuckerkandl, Pauling, Margoliash,
Fitch
• Originally based on comparing proteins based on electrophoresis and later
DNA via DNA-DNA hybridization experiments
• Sanger sequencing (1977) ushers in DNA sequencing
• A variety of techniques and statistical algorithms have been developed
over the decades:
• Maximum Parsimony
• Maximum Likelihood
• Bayesian Inference
• Distance Methods
• Neighbour-Joining

23. Phylogenetic Trees and Evolutionary Genetics:
Molecular Evolution
• Theoretical Framework in the 1960’s: Zuckerkandl, Pauling, Margoliash,
Fitch
• Originally based on comparing proteins based on electrophoresis and later
DNA via DNA-DNA hybridization experiments
• Sanger sequencing (1977) ushers in DNA sequencing
• A variety of techniques and statistical algorithms have been developed
over the decades:
• Maximum Parsimony
• Maximum Likelihood
• Bayesian Inference
• Distance Methods
• Neighbour-Joining

24. Maximum Parsimony

25. Maximum Parsimony
Minimize the amount of change
necessary to describe the
relationship between
organisms/sequences

26. Maximum Parsimony
A
B
C
D
A
C
B
D
A
D
C
B

27. Maximum Parsimony: Informative and Non-
Informative Sites
A
D
C
B
A
C
B
D
A
B
C
D
A aat tcg ctt cta gga atc tgc cta atc ctg
B ... ..a ..g ..a .t. ... ... t.. ... ..a
C ... ..a ..c ..c ... ..t ... ... ... t.a
D ... ..a ..a ..g ..g ..t ... t.t ..t t..
1 2 3 4 5 6 7

28. Maximum Parsimony: Informative and Non-
Informative Sites
A
D
C
B
A
C
B
D
A
B
C
D
A aat tcg ctt cta gga atc tgc cta atc ctg
B ... ..a ..g ..a .t. ... ... t.. ... ..a
C ... ..a ..c ..c ... ..t ... ... ... t.a
D ... ..a ..a ..g ..g ..t ... t.t ..t t..
1 2 3 4 5 6 7

29. Maximum Parsimony: Informative and Non-
Informative Sites
A
D
C
B
A
C
B
D
A
B
C
D
A aat tcg ctt cta gga atc tgc cta atc ctg
B ... ..a ..g ..a .t. ... ... t.. ... ..a
C ... ..a ..c ..c ... ..t ... ... ... t.a
D ... ..a ..a ..g ..g ..t ... t.t ..t t..
1 2 3 4 5 6 7
g
a a
a g g
a a
a
a a
a

30. Maximum Parsimony: Informative and Non-
Informative Sites
A
D
C
B
A
C
B
D
A
B
C
D
A aat tcg ctt cta gga atc tgc cta atc ctg
B ... ..a ..g ..a .t. ... ... t.. ... ..a
C ... ..a ..c ..c ... ..t ... ... ... t.a
D ... ..a ..a ..g ..g ..t ... t.t ..t t..
1 2 3 4 5 6 7
t
g a
c t t
c a
g
a g
c

31. Maximum Parsimony: Informative and Non-
Informative Sites
A
D
C
B
A
C
B
D
A
B
C
D
A aat tcg ctt cta gga atc tgc cta atc ctg
B ... ..a ..g ..a .t. ... ... t.. ... ..a
C ... ..a ..c ..c ... ..t ... ... ... t.a
D ... ..a ..a ..g ..g ..t ... t.t ..t t..
1 2 3 4 5 6 7
a
a g
c a a
c g
a
g a
c

32. Maximum Parsimony: Informative and Non-
Informative Sites
A
D
C
B
A
C
B
D
A
B
C
D
A aat tcg ctt cta gga atc tgc cta atc ctg
B ... ..a ..g ..a .t. ... ... t.. ... ..a
C ... ..a ..c ..c ... ..t ... ... ... t.a
D ... ..a ..a ..g ..g ..t ... t.t ..t t..
1 2 3 4 5 6 7
a
a g
c a a
c g
a
g a
c

33. Maximum Parsimony: Informative and Non-
Informative Sites
A
D
C
B
A
C
B
D
A
B
C
D
A aat tcg ctt cta gga atc tgc cta atc ctg
B ... ..a ..g ..a .t. ... ... t.. ... ..a
C ... ..a ..c ..c ... ..t ... ... ... t.a
D ... ..a ..a ..g ..g ..t ... t.t ..t t..
1 2 3 4 5 6 7
c
c t
t c c
t t
c
t c
t

34. Maximum Parsimony: Challenges
• Enumerating the minimum number of changes on a tree gets
inefficient as the number of leaf nodes increases (Easy)
• Fitch Algorithm Solution
• Evaluating all possible trees becomes impossible as the number of
leaf nodes increases (Hard)
• Number of unrooted trees for N leaf nodes:
• π(i=3 ...n) (2i – 5) (10 Nodes = > 2 million trees)
• Number of rooted trees for N leaf nodes:
• π(i=3 ...n) (2i – 3) (10 Nodes = >34 million trees)

35. Phylogenetic Trees and Evolutionary Genetics
• Performed on Amino Acid or Nucleotide sequences
• Performed on basis of single-genes, multiple genes, or whole
genomes
• Typically rely on:
• Multiple sequence alignment
• Model of evolution
• Amino acid or nucleic acid exchange probabilities
• Rates of substitution
• Site classes

36. Interesting Deviations

37. Horizontal Gene Transfer

38. Horizontal Gene Transfer

39. Horizontal Gene Transfer

40. Horizontal Gene Transfer

41. Horizontal Gene Transfer in Animals

42. Horizontal Gene Transfer in Animals

43. Horizontal Gene Transfer and Mammalian
Reproduction

44. Horizontal Gene Transfer and Mammalian
Reproduction
• Multiple Independent
acquisitions of Syncytin genes
• Syncytin gene acquisition
primarily in lineages with
moderate to highly invasive
placental type
• Cell fusion and
immunosuppresion

45. Human Evolution

46. Human Population Movement

47. Human Population Movement

48. Human Evolution: Neanderthal and
Denisovan Interbreeding

49. Human Evolution: Neanderthal and
Denisovan Interbreeding

50. Human Evolution: Neanderthal and
Denisovan Interbreeding

51. Recent Human Evolution and Population
Movements

52. Recent Human Evolution: Agriculture and
Immunology
• Evolution hasn’t stopped in humans, although modern medicine and
society has shifted selection pressures
• SLC22A4: Ergothioneine absorption. Variant with enhanced activity arises
and spreads in Neolithic Europe with the rise of agriculture and shift to
wheat consumption
• Lactase persistence arises in multiple populations around the world
• Lighter skin of Europeans relatively recent. First with arrival of migrants
from Turkey <9,000 years ago, then with a second mutations sometime
more recently
• Height (Particularly linked to Yamnaya introgression in Northern
Europeans)

53. "Nothing in Biology Makes Sense Except in the
Light of Evolution"
-- Theodosius Dobzhansky