Genome Evolution © Amos Tanay, The Weizmann Institute Genome evolution 2010 Lecture 1: evolutionary ideas Amos Tanay, Ziskind 204, ext 3579 עמוס תנאי [email protected]

Genome Evolution © Amos Tanay, The Weizmann Institute

Genome evolution 2010

Lecture 1: evolutionary ideas

Amos Tanay, Ziskind 204, ext 3579 עמוס תנאי

[email protected]

http://www.wisdom.weizmann.ac.il/~atanay/GenomeEvo/


Linnaeus - SpeciesSwedish (1708-1777)

Developed hierarchical taxonomy (and pioneered scientific classification)

Even though his classification scheme included mythic monsters, Goethe said he is comparable only to Shakespeare and Spinoza


Lemarck - adaptation

Jean Baptiste Lamarck

French (1744-1829)

First specializing in invertebrate zoology, collecting samples for museums-gardens

1 paper in first 6 years as professor

Controversial (geophysics, chemistry..)

The “first” evolutionary theorist

Complexification force Adaptive force

“Forming order”


Darwin – natural selection

Darwin

English (1809-1882)

Dislike surgeon studies Famous Beagle tripMaltussian growthSurvival of the fittest

Wallace“Origin of species” (1859)

First print: 1250 copies

The Descent of Man, and Selection in Relation to Sex


Fischer,Haldane,Wright – Population genetics

Fischer

Haldane

Wright

Sewall Wright: (American 1889-1988)Geneticist (Guinea pigs)Genetic drift, inbreeding..

Ronald Fischer: (English 1890-1962)Start by studying crop variationInvented ANOVA, Max likelihood, non parameteric statistics, Fischer information Qunatitative genetics, diffussion approximation

J.B.S Haldane: (English 1892-1964)Aristocrat familyBriggs-haldane kinetics (Michaelis-Mentel Alternative)Gene frequenciesPopular author and communicator


Models of population genetics

A

a

A

a

Generations/time

Modeling the dynamics of allele frequencies

Blue allele

Yellow allele

AA

aa

AaGenerations/time AA

aa

Aa



Modeling evolution

A

a

A

a

Generations/time


Blue allele

Yellow allele

t t+1


DobzhanskyMayr

0.717

0.573

0.504

0.302

0.657

0.3390.008

0.007

0.032

0.005

0.009

0.000

0.000

0.000

0.000

0.005

0.010

0.000

0.000

0.126

0.068

0.004

0.002

0.000

0.000

0.000

0.014

0.224

0.411

0.106

1589.0SRF

3299.0RTF

4995.0H

0272.0H

3062.0H

Frequency of recessive allele (blue flower color) in “desert snow” flowers (Lynanthus parruae)

Mayr,Dobzhansky – Synthesis

The modern synthesis

DarwinMendel

Ernst Mayr: German/American (1904-2005)

Tropical explorations: birds

SpeciationBiogeographyPhilosophy of Science: rejected reductionism

Theodosius Dobzhansky (Ukrainan/American 1900-1975)

Genetics and the origin of species

Flies/plants field studies


The code – Genomic sequences

The machine – Protein networks in cells

…ACGAATAGCAAATGGGCAGATGGCAGTCTAGATCGAAAGCATGAAACTAGATAGCAT…

Watson,Crick - Code

Jacob

Monod

Crick


Kimura: Stochasticity, Neutrality

Kimura



…ACGAATAGCAAAAGGGCAGATGGCATTCTAGATCGAAAGCATGAAACTAGATAGCAT…



Selectionists: Mutations are occurring by chance - some get selected and these are the changes we see between genomes

Kimura et al.: Most of the changes between genomes are neutral - not a result of selection


Neutral Evolution

Kimura’s analytic achievement was the solution of a certain class of Partial Differential Equations that describe the dynamic of allele frequencies under neutral evolution

),()(2

1),()(),(

2txxV

xtxxM

xtx

t

But we can try and understand the essence of neutral evolution even without fancy mathematics:

t=1 t=n

Last common ancestor

Neutral changesAlong the path are fixated

Coalescent time


Felsenstein (and many others): Phylogenetics, probability

Computational methods for sequence analysis

Construct phylogenies from genomes

Tree of live? Origin of early forms?

Gould-Eldrege:Punctuated equilibrium

Better and better fossil record

Evolution/speciation rate: bursts

Joe Felsenstein


Ohno: duplication

Susumo Ohno – (1928-2000)

Genome evolution is facilitated by duplications

Underlying concept: modularity

Based on protein families at start

(Can you think of the challenges in explaining protein duplication?)


Yeast Genome duplication

• The budding yeast S. cerevisiae genome have extensive duplicates

• We can trace a whole genome duplication by looking at yeast species that lack the duplicates (K. waltii, A. gosypii)

• Only a small fraction (5%) of the yeast genome remain duplicated


• How can an organism tolerate genome duplication and massive gene loss?

• Is this critical in evolving new functionality?


Jacob/Monod-> Evolving programs

F. Jacob(b 1920)

J. Monod(1910-1976)

Regulation

Development

Evo-Devo

Davidson..Gould..Lewis..


Maynard-Smith: interaction

1920-2004

Interaction between individuals inside a species: different strategies

Introducing game theoretic ideas to evolution

What is the basic unit of evolution?

Genes may compete and interact in a population


The Genomics revolution


From hundreds to billions loci….

Protein analysis

1960

1970

1980

1990

2000

2010

x1 x2 x3 x4 x5 x6

Phylogenetic reconstruction

Multiple copies of the same Markov process

Universal Q

Genome = many independent nucleotides


From hundreds to billions loci….

1960

1970

1980

1990

2000

2010

x1 x2 x3 x4 x5 x6

Multiple copies of the same Markov process

Universal Q

Genome = many independent nucleotides


Humans and Chimps

• Where are the “important” differences?• How did they happen?

~5-7 million years

3X109

{ACGT}3X109

}ACGT{

Genome alignment


Ma

rmo

se

t

Ma

ca

qu

e

Ora

ng

uta

n

Ch

imp

Hu

ma

n

Bab

oo

n

Gib

bo

n

Gor

illa

0.5%0.5%

0.8%

1.5%

3%

9%

1.2%

Where are the “important” differences?

How did new features were gained?


Antibiotic resistance: Staphylococcus aureus

Timeline for the evolution of bacterial resistance in an S. aureus patient (Mwangi et al., PNAS 2007)

•Skin based•killed 19,000 people in the US during 2005 (more than AIDS)•Resistance to Penicillin: 50% in 1950, 80% in 1960, ~98% today•2.9MB genome, 30K plasmid

How do bacteria become resistant to antibiotics?Can we eliminate resistance by better treatment protocols, given understanding of the evolutionary process?


Vanco.RifampiOxaciliDapto.

20/710.0120.750.01

20/9416250.05

1/106160.750.05

6/108161.51.0

13/108160.751.0

Mutations

1 2 3 4-6 7 8 9 10 11 12 13 14 15…18Resistance to Antibiotics

S. Aureus got found just few “right” mutations and survived multi-antibiotics

Ultimate experiment: sequence the entire genome of the evolving S. aureus


“Junk” and ultraconservation

12MB ~6000 genes

100MB ~20,000 genes

3GB ~27,000 genes

Baker’s yeast

The worm c.elegans

Humans

1 cell

~1000 cells

~50 trillions cells


Archeological genomics reveal sequences of extinct species!


From: Lynch 2007


ENCODE Data

exon exon exon exonintron intergenicintergenic intronintron


Course duties

•Exercises – 70% of the grade

•Submit on time

•Present a paper

Topics:

Population genetics: models, drift, selectionSpecies, phylogeniesProbabilistic models for sequence evolutionComparative genomics: inferring selectionQuantitative traits evolutionEvolution of transcription regulation

Mathematics: Markov processes, algorithms for probabilistic inference, some statisticsIntroduced without assuming much prior knowledge, buy may require work to understand..

Documents

Genome Evolution © Amos Tanay, The Weizmann Institute Genome evolution 2010 Lecture 1: evolutionary ideas Amos Tanay, Ziskind 204, ext 3579 עמוס תנאי [email protected]