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Evolutionary GeneticsHuman Genetics
http://slideshare.net/[email protected]
March 7th, 2016Dr. Dan Gaston
"Nothing in Biology Makes Sense Except in the Light of Evolution"
-- Theodosius Dobzhansky
Evolutionary Genetics
Genetics Evolution
Evolutionary Genetics
Population Genetics Evolution
Evolutionary Genetics: Darwinian Origins
Voyage of The Beagle: 1831-1836Origin of Species: November 24th, 1859
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
The Forces of Evolution
•Mutation•Genetic Drift
•Selection
Mutation
Genetic Drift
Selection• W = 1 – s
• W: Fitness• s: Selection Coefficient
• s = 1 (Lethal)• s = 0 (No difference in fitness)
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
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
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
Evidence for Near Neutrality• Prediction: Fixation of Neutral sites will occur at the rate of mutation
(or nearly so for near neutrality)
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
Nearly Neutral Theory of Evolution
Neutral Evolution becomes the Null Hypothesis in Evolutionary Biology. It is the default assumption in the absence of evidence of selection
Mutation
Phylogenetic Trees and Models of Evolution
Phylogenetic Trees
Phylogenetic Trees
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
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
Maximum Parsimony
Maximum Parsimony
Minimize the amount of change necessary to describe therelationship between organisms/sequences
Maximum ParsimonyA
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Maximum Parsimony: Informative and Non-Informative Sites
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Maximum Parsimony: Informative and Non-Informative Sites
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Maximum Parsimony: Informative and Non-Informative Sites
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Maximum Parsimony: Informative and Non-Informative Sites
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Maximum Parsimony: Informative and Non-Informative Sites
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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)
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
Interesting Deviations
Horizontal Gene Transfer
Horizontal Gene Transfer
Horizontal Gene Transfer
Horizontal Gene Transfer
Horizontal Gene Transfer in Animals
Horizontal Gene Transfer in Animals
Horizontal Gene Transfer and Mammalian Reproduction
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
Human Evolution
Human Population Movement
Human Population Movement
Human Evolution: Neanderthal and Denisovan Interbreeding
Human Evolution: Neanderthal and Denisovan Interbreeding
Human Evolution: Neanderthal and Denisovan Interbreeding
Recent Human Evolution and Population Movements
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)
"Nothing in Biology Makes Sense Except in the Light of Evolution"
-- Theodosius Dobzhansky