dr. walter salzburger molecular...

Herbstsemester 2008Freitag 13:15 - 15 Uhr

2 Kreditpunkte

MolecularEvolution

Dr. Walter Salzburger

Structure | i

Structure of the course:

The Nature of Molecular Evolution

Molecules as Documents of Evolutionary History

Inferring Molecular Phylogeny!

Models of Molecular Evolution

The Neutral Theory and Adaptive Evolution

Evolutionary Genomics

From DNA to Diversity

Lectures Papers Lab

Lectures:

! The Nature of Molecular Evolution

!Molecules as Documents of Evolutionary History

! Inferring Molecular Phylogeny! ! ! ! ! ! ! !

!Models of Molecular Evolution

! The Neutral Theory and Adaptive Evolution

! Evolutionary Genomics

! From DNA to Diversity

3.10.

17.10.

31.10.

14.11.

5.12.

19.12.

?.?.

Structure | ii

Page and Holmes (1998) Molecular Evolution

– A Phylogenetic Approach, Blackwell

Publishing

Nei and Kumar (2000) Molecular Evolution

and Phylogenetics; Oxford University Press

Avise (2004) Molecular Markers, Natural

History, and Evolution; Sinauer

Carroll, Grenier and Weatherbee (2005) From

DNA to Diversity; Blackwell

Useful books:

Structure | iii

Examination:

Report

+Written Exam

Structure | iv

Learning targets:

Introduction to the field of Molecular Evolution

Key concepts and methods of Molecular Evolution

Key players in the field of Molecular Evolution

Key papers in Molecular Evolution

Milestones in Molecular Evolution

Goal | v

The Nature of MolecularEvolution

Walter Salzburger

A brief history | 1

Molecular evolution deals with the

process of evolution at the scale

of DNA, RNA and proteins

Charles R. Darwin publishes “On the origin of species

by means of natural selection” and establishes the

theory of evolution

1859

Charles R. Darwin (1809-1882)

A brief history | 2

1866Gregor Mendel publishes “Experiments in plant

hybridization”. This paper established what

eventually became formalized as the Mendelian

laws of inheritance.

Gregor Mendel

(1822-1884)

A brief history | 3

1866Gregor Mendel publishes “Experiments in plant

hybridization”. This paper established what

eventually became formalized as the Mendelian

laws of inheritance.

A brief history | 4

1869Johann Friedrich Miescher extracts what comes to be

known as DNA from the nuclei of white blood cells.

Johann F. Miescher (1844-1895)

A brief history | 5

1900Independently of one another, Hugo de Vries

(1848-1935), Erich von Tschermak-Seysenegg

(1871-1962) and Carl Correns (1864-1933)

rediscover Mendel’s published, but long neglected,

paper outlining the basic laws of inheritance.

A brief history | 6

Hugo de Vries Erich v. Tschermack Carl Correns

Walter Sutton

(1877-1916)Theodor Boveri

(1862-1915)

1902Theodor Boveri and Walter Sutton propose that

chromosomes bear heritary factors in accordance

with Mendelian laws.

A brief history | 7

Thomas H. Morgan establishes the chromosomal

theory of inheritance. He also discovered the

recombination of homologous chromosomes

during meiosis.

Thomas Hunt Morgan (1866-1945)

1910

A brief history | 8

Oswald T. Avery (1877-1955), Maclyn McCarty

(1911-2005) and Colin MacLeod (1909-1972) identify

deoxyribonucleic acid (DNA) as the “transforming

principle”.

Oswald T. Avery

(1877-1955)

1944

A brief history | 9

Erwin Chargaff discovers regularity in proportions of

DNA bases. In all organisms he studied, the

amount of adenine (A) equaled that of thymine (T),

and guanine (G) equaled cytosine (C).

Erwin Chargaff (1905-2002)

1950

A brief history | 10

James Watson and Francis Crick discover the double

helical structure of the DNA and that this structure

meets the unique requirements for a substance

that encodes genetic information.

James D. Watson (1928-)

Francis H. C. Crick (1916-2004)

1953


1953


Discovery of messenger RNA (mRNA) by Sydney

Brenner (1927-), Francis Crick (1916-2004), Francois

Jacob (1920-) and Jacques Monod (1910-1976).

1960


Discovery of restriction endonucleases by Werner

Arber (1929-), Hamilton O. Smith (1931-) and Daniel

Nathans (1928-1999).

1968


Frederick Sanger (1918-) and Walter Gilbert (1932)

develop techniques for DNA sequencing1977


Walter Gilbert Frederick Sanger

Kary B. Mullis (1944-) invents and helps to develop

the polymerase chain reaction (PCR)1983


Kary B. Mullis

1,830,137 bp of Hamophilus influenzae sequenced:

the first genome of a free living organisms

determined

1995



Caenorhabditis elegans sequenced

1998

Drosophila melanogaster sequenced

2000

Homo sapiens sequenced

2001


GeneticOrganization

cellchromosome

gene

protein

Genetic Organization | 1

desoxyribonucleic acid (DNA)


pyrimidines

purines

DNA double helix


cellchromosome

gene

protein


DNA

mRNA

protein

transcription

translation


transcription


translation


protein

structure


The genetic code*

*Note that there is not just one ‘universal’ genetic code!


The degenerated genetic code

4-fold degenerated 2-fold degenerated


The Nature of MolecularEvolution

The Nature of Molecular Evolution | 1

Molecular evolution deals with the

process of evolution at the scale

of DNA, RNA and proteins


! Natural populations show variation at all levels, from gross

morphology to DNA sequences. Natural selection can only

operate, if heritable variation exists.

! Natural variation is generated by two processes:

recombination mutation

“reshuffling” of genetic material

by introducing or breaking up

physical linkage

generation of new genetic

variation by mistakes during the

copying of a DNA strand

! New mutations are only transmitted to the next generation, if

they occur in germinal tissue!


“The primary cause of evolution is the mutational change of genes”

Nei and Kumar (2000)

nucleoide

substitution

insertion/

deletion

gene or genome

duplication

chromosome

rearrangements


Nucleotide substitutions

original DNA sequence:

C C G C T C G T C A A C T A G

GLY GLU GLN LEU ILE

C C G C T T G T C A A C T A G

GLY GLU GLN LEU ILE

C > T

synonymous mutation:

C C G C T C A T C A A C T A G

GLY GLU STOP!

G > Astop mutation:

C C G C C T C G T C A A C T A

GLY GLY ALA VAL ASP

insert Cframeshift mutation:

C C G C T C G T C C A C T A G

GLY GLU GLN ILE ILE

A > C

non-synonymous mutation:

TRANSITION

TRANSITION

TR

AN

SV

ER

SIO

NT

RA

NS

VE

RS

ION

Transition mutations outnumber transversions!

Nucleotide substitutions

Genome duplication

Sw

alla

(2006)

Hox gene clusters

Chromosomal rearrangements

F G HA B C D E

F G HA E

F G HA B C D E

F G HA B C D E A B C D E Q RN O P

deletion

A E D C B F G H

F G H F G HA B C D E

A B C O N Q RE D P

duplication

inversionreciprocal

translocation