Molecular Evolution and Phylogenetic Analysis of Proteins

This course is still under construction and will be updated regularly

A graduate course compiled by Fred R. Opperdoes

Research Unit for Tropical Diseases,"Christian de Duve" Institute of Cellular Pathology and Laboratory of Biochemistry, Université Catholique de Louvain, Brussels, Belgium

Theoretical part

Contents

• Introduction
• Ribosomal RNA or protein sequences for phylogenetic inference?
• Arguments in favour of a phylogenetic analysis of the protein rather than the DNA
  • Codon bias
  • The long time horizon
  • Advantages of the translation of DNA into protein
  • Nature of sequence divergence in proteins (the PAM)
  • Proteins evolve at different rates
  • Introns and non-coding DNA
  • Multi gene families
  • Protein is the unit of selection
  • RNA editing
  • Some good advice
• Construction of protein sequence alignments
  • Alignment of two protein sequences
  • The visual method
  • Computer algorithms
  • Multiple sequence alignment
  • Manual adjustment of a protein alignment
• Methods for the inference of protein phylogeny
  • Introduction
  • Methods available for tree construction
  • How to root an unrooted tree?
  • How to use the tree-construction programs?
  • Limitations of the various methods
  • Complications with paralogous genes

Practical part

Some practical examples

• Example 1: cytochrome oxidase subunit II
• Example 2: hypoxanthine-guanine phosphoribisyl transferases
• Demos of a Protein Analysis Projects carried out on the Web
  • The MDH gene of Phytomonas
  • The enigma of the Leismanial GPD gene
• Practical course

Supplementary reading

• Molecular Evolution by David R. Nelson
• Bioinformatics by Clare Sansom (with many interesting WWW sites)
• The Earliest Memories of Life on Earth by John M. Hayes
• Biological background for sequence analysis by David Steffen

Useful addresses

• The databases available on the BEN computer.
• Addresses used in this course
• Mark van Ranst's gene machine
• The Infobiogen server

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Where to find software

• List of Phylogeny software compiled by Joe Felsenstein
• List of multiple alignment software complied by Georg Fuellen

Introduction

This course has been designed for interactive use from a computer with a web browser such as Netscape. The course will be made available on floppy disk or on CD-ROM and can also be accessed via the internet at the following URL: <http://www.icp.ucl.ac.be/~opperd/protein_course/proteins.html> .

Although this course can be studied using the floppy disk on a stand alone computer, access to mail- and file servers and to molecular biology databases is only available when the computer has a direct connection to the Internet. In that case a floppy disk is not required and the course can be started by linking to the above URL from within your web browser.

This course is meant to provide insight in the mechanisms of evolution to which proteins are subjected and how the accumulation of mutations in polypeptides may provide us with useful information about their evolutionary history and that of the organisms that contain them. I shall explain in very general terms how a biologist goes about using computer programs for sequence analysis and the inference of evolution from protein sequences. I hope this course will provide direction as to how to approach this difficult subject. The course is not only meant to be a theoretical one, but also tends to provide as much as possible examples to illustrate the topics. It contains many hyperlinks to web sites somewhere on the Internet which can be accessed for further information or for the use of software that is not directly available to the student. All of the software discussed in this course is freely available on the web and where possible indications are given as to how these can be obtained. The theoretical part is followed by a hands on practical course where each student will have the opportunity to surf the internet and get acquainted with the sequence databases, the sequence analysis tools and servers that have been made available to the community to carry out a number of the computational tasks.

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Last updated: 28 September 1997.