Dr. Walter Salzburger Molecular Evolution

Herbstsemester 2008 Freitag 13:15 - 15 Uhr 2 Kreditpunkte

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 Structure | ii

Lectures: ! The Nature of Molecular Evolution 3.10. ! Molecules as Documents of Evolutionary History 17.10. ! Inferring Molecular Phylogeny!!!!!!!!31.10. ! Models of Molecular Evolution 14.11. ! The Neutral Theory and Adaptive Evolution 5.12. ! Evolutionary Genomics 19.12. ! From DNA to Diversity ?.?.

Structure | iii

Useful books:

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 Structure | iv

Examination:

+ Written Exam Report

Goal | v

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 Walter Salzburger The Nature of Molecular Evolution

A brief history | 1

Molecular evolution deals with the process of evolution at the scale of DNA, RNA and proteins A brief history | 2

Charles R. Darwin publishes “On the origin of species 1859 by means of natural selection” and establishes the theory of evolution

Charles R. Darwin (1809-1882)

A brief history | 3

Gregor Mendel publishes “Experiments in plant 1866 hybridization”. This paper established what eventually became formalized as the Mendelian laws of inheritance.

Gregor Mendel (1822-1884) A brief history | 4

Gregor Mendel publishes “Experiments in plant 1866 hybridization”. This paper established what eventually became formalized as the Mendelian laws of inheritance.

A brief history | 5

Johann Friedrich Miescher extracts what comes to be 1869 known as DNA from the nuclei of white blood cells.

Johann F. Miescher (1844-1895) A brief history | 6

Independently of one another, Hugo de Vries 1900 (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.

Hugo de Vries Erich v. Tschermack Carl Correns

A brief history | 7

Theodor Boveri and Walter Sutton propose that 1902 chromosomes bear heritary factors in accordance with Mendelian laws.

Walter Sutton Theodor Boveri (1877-1916) (1862-1915) A brief history | 8

Thomas H. Morgan establishes the chromosomal 1910 theory of inheritance. He also discovered the recombination of homologous chromosomes during meiosis.

Thomas Hunt Morgan (1866-1945)

A brief history | 9

Oswald T. Avery (1877-1955), Maclyn McCarty 1944 (1911-2005) and Colin MacLeod (1909-1972) identify deoxyribonucleic acid (DNA) as the “transforming principle”.

Oswald T. Avery (1877-1955) A brief history | 10

Erwin Chargaff discovers regularity in proportions of 1950 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)

A brief history | 11

James Watson and Francis Crick discover the double 1953 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) A brief history | 12

1953

A brief history | 13

Discovery of messenger RNA (mRNA) by Sydney 1960 Brenner (1927-), Francis Crick (1916-2004), Francois Jacob (1920-) and Jacques Monod (1910-1976). A brief history | 14

Discovery of restriction endonucleases by Werner 1968 Arber (1929-), Hamilton O. Smith (1931-) and Daniel Nathans (1928-1999).

A brief history | 15

Frederick Sanger (1918-) and Walter Gilbert (1932) 1977 develop techniques for DNA sequencing

Walter Gilbert Frederick Sanger A brief history | 16

Kary B. Mullis (1944-) invents and helps to develop 1983 the polymerase chain reaction (PCR)

Kary B. Mullis

A brief history | 17

1,830,137 bp of Hamophilus influenzae sequenced: 1995 the first genome of a free living organisms determined A brief history | 18

1998 Caenorhabditis elegans sequenced

2000 Drosophila melanogaster sequenced

A brief history | 19

2001 Homo sapiens sequenced Genetic Organization

Genetic Organization | 1

chromosome cell

gene

protein Genetic Organization | 2

desoxyribonucleic acid (DNA)

Genetic Organization | 3

DNA double helix pyrimidines

purines Genetic Organization | 4

chromosome cell

gene

protein

Genetic Organization | 5

DNA

transcription mRNA

translation

protein Genetic Organization | 6

transcription

Genetic Organization | 7

translation Genetic Organization | 8

protein structure

Genetic Organization | 9

The genetic code*

*Note that there is not just one ‘universal’ genetic code! Genetic Organization | 10

The degenerated genetic code

4-fold degenerated 2-fold degenerated

The Nature of Molecular Evolution The Nature of Molecular Evolution | 1

Molecular evolution deals with the process of evolution at the scale of DNA, RNA and proteins

The Nature of Molecular Evolution | 2

! 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 generation of new genetic by introducing or breaking up variation by mistakes during the physical linkage copying of a DNA strand The Nature of Molecular Evolution | 3

! New mutations are only transmitted to the next generation, if they occur in germinal tissue!

The Nature of Molecular Evolution | 4

“The primary cause of evolution is the mutational change of genes” Nei and Kumar (2000)

nucleoide substitution chromosome gene or genome rearrangements insertion/ duplication deletion Nucleotide substitutions synonymous mutation: C > T

CCG CTT GTC AAC TAG GLY GLU GLN LEU ILE

non-synonymous mutation: A > C

CCG CTC GTC C AC TAG original DNA sequence: GLY GLU GLN ILE ILE CCG CTC GTC AAC TAG GLY GLU GLN LEU ILE frameshift mutation: insert C

CCG CCT CGT CAA CTA GLY GLY ALA VAL ASP

stop mutation: G > A

CCG CTC A TC AAC TAG GLY GLU STOP!

Nucleotide substitutions

TRANSITION TRANSVERSION TRANSVERSION

TRANSITION Transition mutations outnumber transversions! Genome duplication

Hox gene clusters Swalla (2006)

Chromosomal rearrangements

A B C D E F G H A B C D E F G H

deletion duplication

A E F G H A B C D E F G H F G H

A B C D E F G H A B C D E N O P Q R

reciprocal inversion translocation A E D C B F G H A B C O N E D P Q R