Bioinformatics for Human Biologists

1. Bioinformatics for Human Biologists Rasmus Wernersson, Associate Professor Center for Biological Sequence Analysis, DTU [raz@cbs.dtu.dk - http://www.cbs.dtu.dk/~raz/]

2. Course outline

3. DTU survival guide

4. This is a hands-on course • The major part of the course is computer exercises • We get to use the actual methods • We get to use “live” online database • Reporting: • Short “log book” on each exercise

5. Everything is linked from the course programme

6. Background information On evolution and sequences

7. Classification: Linnaeus Carl Linnaeus 1707-1778

8. Classification: Linnaeus • Hierarchical system • Kingdom • Phylum • Class • Order • Family • Genus • Species

9. Classification depicted as a tree

10. No “mixed” animals Source: www.dr.dk/oline

11. Classification depicted as a tree Species Genus Family Order Class

12. Comparison of limbs Image source: http://evolution.berkeley.edu

13. Theory of evolution Charles Darwin 1809-1882

14. Phylogenetic basis of systematics • Linnaeus: Ordering principle is God. • Darwin: Ordering principle is shared descent from common ancestors. • Today, systematics is explicitly based on phylogeny.

15. Natural Selection: Darwin’s four postulates • More young are produced each generation than can survive to reproduce. • Individuals in a population vary in their characteristics. • Some differences among individuals are based on genetic differences. • Individuals with favorable characteristics have higher rates of survival and reproduction. • Evolution by means of natural selection • Presence of ”design-like” features in organisms: • Quite often features are there “for a reason”

16. Evolution at the sequence level

17. About DNA • DNA contains the recipes of how to make protein / enzymes. • Every time a cells divides it’s DNA is duplicated, and each daughter cell gets a copy.

18. The DNA alphabet • The information in the DNA is written in a four letter code: A, T, G, C. • The DNA can be “sequenced” and the result stored in a computer file. • ATGGCCCTGTGGAT

19. Ribose 5 4 1 3 2 Deoxyribose 5 4 1 3 2 DNA is always written 5’  3’ 3’ 5’ AGCC 3’ 3’ TCGG 5’ 5’ ATGGCCAGGTAA 3’ 5’ 5’ 3’ DNA backbone: http://en.wikipedia.org/wiki/DNA (Deoxy)ribose: http://en.wikipedia.org/

20. Can DNA be changed? • ATGGCCCTGTGGATGCG

21. Can DNA be changed? • ATGGCCCTGTGGATGCG • ATGGCCCTATGGATGCG

22. A history of mutations ATGGCAATGTGGATGCA ATGGCCCCGTGGAACCG ATGTCCCCGTGGATGCG ATGGCCCCGTGGATGCG ATGGCCCTGTGGATGCG Time ATGGCCCTGTGTATGCG

23. 6 5 3 “DNA alignment” • Species1: ATGGCAATGTGGATGCA • Species2: ATGGCCCCGTGGAACCG • Species3: ATGTCCCCGTGGATGCG

24. Real life example: Alignment • Insulin from 7 different species • Homo: ATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGCGCTGCTGGCCCTCTGGGGACCTGACCCAGCCGCAGCCTTTGTGAA • Pan: ATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGTGCTGCTGGCCCTCTGGGGACCTGACCCAGCCTCGGCCTTTGTGAA • Sus: ATGGCCCTGTGGACGCGCCTCCTGCCCCTGCTGGCCCTGCTGGCCCTCTGGGCGCCCGCCCCGGCCCAGGCCTTCGTGAA • Ovis: ATGGCCCTGTGGACACGCCTGGTGCCCCTGCTGGCCCTGCTGGCACTCTGGGCCCCCGCCCCGGCCCACGCCTTCGTCAA • Canis: ATGGCCCTCTGGATGCGCCTCCTGCCCCTGCTGGCCCTGCTGGCCCTCTGGGCGCCCGCGCCCACCCGAGCCTTCGTTAA • Mus: ATGGCCCTGTTGGTGCACTTCCTACCCCTGCTGGCCCTGCTTGCCCTCTGGGAGCCCAAACCCACCCAGGCTTTTGTCAA • Gallus: ATGGCTCTCTGGATCCGATCACTGCCTCTTCTGGCTCTCCTTGTCTTTTCTGGCCCTGGAACCAGCTATGCAGCTGCCAA

25. Real life example: Tree

26. Interpretation of Multiple Alignments Conserved features assumed to be important for functionality For instance: conserved pairs of cysteines indicate possible disulphide bridge

27. Sequences are related • Darwin: all organisms are related through descent with modification • Prediction: similar molecules have similar functions in different organisms Protein synthesis carried out by very similar RNA-containing molecular complexes (ribosomes) that are present in all known organisms

28. Sequences are related, II Related oxygen-binding proteins in humans