1. Sequencing and personal genomics

2. Genomics Genomics is the study of genomes
It involves determining the genetic sequences of bases on DNA molecules in different species
Bioinformatics involves the use of computation and statistics to compare the genomes of different species
The human genome was sequenced by 2003

3. …continued
The results of sequencing can allow the evolutionary relatedness of species to be studied
It is possible to estimate the times at which lineages diverged with evidence also provided by fossils
This allows the construction of phylogenetic trees

6. On the basic tree… Label the last universal ancestor of A – E
The last ancestor lived 9 million years ago, add a time scale bar between this last ancestor and A – E
Label the common ancestor of species A and B
Label the common ancestor of species D and E
Of which species are x and y the common ancestors?
When did the last ancestor of C, D and E live?

7. Molecular Clocks
Over time, nucleic acid base sequences and the amino acid sequence in the proteins they code for change
The changes are usually caused by single nucleotide polmorphisms (SNPs)
SNPs are usually substitution mutations in the DNA sequences
These mutations often lead to changes in the amino acid sequences in the proteins they code for

8. …continued
It is therefore possible to compare sequence data in an attempt to map out a timescale for evolution
The greater the difference in sequence data the further apart in time are the organisms which provided the sequences
Several protein based molecular clocks are well known

10. …continued
Molecular clocks are used alongside the fossil record to construct phylogenetic trees which represent the history of life
The fossils are needed because they can be accurately dated – sequence data and molecular clocks do not give absolute dating
Read the text and try the questions on the phylogenetic history of homonids

11. …continued
Phylogenetics has provided evidence for three main domains of life which evolved from a universal ancestor…
Bacteria – prokayotic
Archaea – mostly prokaryotic and live in extreme environments eg hot springs
Eukaryotes – having cells with a true nucleus [fungi, plants and animals]

13. …continued
Make a sketch of a phylogenetic tree showing a universal ancestor giving rise to the three main domains of life – inspiration from Tp103

14. Evolutionary Events
Complete the table to show the main events of evolution

15. T p 106
Q 1 – 3 in day books

16. Sequencing Genomes
The genomes of a number of organisms have been sequenced
The priority has been to sequence disease causing organisms, pest species and organisms that are important models for research
Comparison of genomes confirms that much of the genome is conserved across different organisms.

17. Organism
Type
Relevance
Genome size
Number of genes predicted
Organization
Year of completion
Guillardia theta
Cryptomonad
Model organism
0.551 Mb (nucleomorph genome only)
465,[1] 513, 598 (UniProt)
Canadian Institute of Advanced Research, Philipps-University Marburg and the University of British Columbia
2001[1]
Plasmodium falciparum Clone:3D7
Apicomplexan
Human pathogen (malaria)
22.9 Mb
5,268[2]
Malaria Genome Project Consortium
2002[2]
Plasmodium yoelii yoelii Strain:17XNL
Rodent pathogen (malaria)
23.1 Mb
5,878[3]
TIGR and NMRC
2002[3]
Cryptosporidium hominis Strain:TU502
Human pathogen
10.4 Mb
3,994[4]
Virginia Commonwealth University
2004[4]
Cryptosporidium parvum C- or genotype 2 isolate
16.5 Mb
3,807[5]
UCSF and University of Minnesota
2004[5]
Thalassiosira pseudonana Strain:CCMP 1335
Diatom
34.5 Mb
11,242[6]
Joint Genome Institute and the University of Washington
2004[6]

18. Organism
Type
Relevance
Genome size
Number of chromosomes
Number of genes predicted
Organization
Year of completion
Arabidopsis thaliana Ecotype:Columbia
Wild mustard Thale Cress
Model plant
119 Mb 5
25,498,[7] 27,400,[8] 31,670 (UniProt)
Arabidopsis Genome Initiative[9]
2000[7]
Cyanidioschyzon merolae Strain:10D
Red alga
Simple eukaryote
16.5 Mb 20
5,331[10]
University of Tokyo, Rikkyo University, Saitama University and Kumamoto University
2004[10]
Oryza sativa ssp indica
Rice
Crop and model organism
420 Mb 12
32-50,000[11]
Beijing Genomics Institute, Zhejiang University and the Chinese Academy of Sciences
2002[11]
Ostreococcus tauri
Green alga
Simple eukaryote, small genome
12.6 Mb
7,969 (UniProt)
Laboratoire Arago
2006[12]
Populus trichocarpa
Balsam poplar or Black Cottonwood
Carbon sequestration, model tree, commercial use (timber), and comparison to A. thaliana
550 Mb 19
45,555[13]
The International Poplar Genome Consortium
2006[13]

19. Organism
Type
Relevance
Genome size
Number of genes predicted
Organization
Year of completion
Anopheles gambiae Strain: PEST
Mosquito
Vector of malaria
278 Mb
13,683[26]
Celera Genomics and Genoscope
2002[26]
Caenorhabditis elegans Strain:Bristol N2
Nematode
Model animal
100 Mb
19,000[20]
Washington University and the Sanger Institute
1998[20]
Drosophila melanogaster
Fruit fly
165 Mb
13,600[21]
Celera, UC Berkeley, Baylor College of Medicine, European DGP
2000[21]
Homo sapiens
Human
3.2 Gb[22]
20,251 (UniProt)
Human Genome Project Consortium and Celera Genomics
Draft 2001[23][24] Complete 2006[25]
Takifugu rubripes
Puffer fish
Vertebrate with small genome
390 Mb
22–29,000[27]
International Fugu Genome Consortium[28]
2002[29]

20. Fugu genome Takifugu rubripes is a pufferfish
A feature of this species is that it has a very small genome, which is used as a ‘reference’ for identifying genes and other elements in human and other vertebrate genomes
The coding sequences are very similar in size to the human genome but the non-coding sequences are very much smaller
The genome was published in 2002, the first vertebrate genome to be made publicly available after that of humans

21. Pufferfish

22. Human and Fugu compared

23. Comparison of genes in humans and in the Fugu

25. Pharmacogenetics
It is possible to sequence the genome of an individual human being.
Many diseases have a genetic risk component and so personal genomics could lead to personalised medicine
It offers increased information on the likelihood of a treatment being successful in a specific individual
There is significant difficulty in distinguishing between neutral mutations and potentially harmful mutations in genes and in regulatory genetic sequences

26. Example
A recent breakthrough in pharmacogenetics identified a polymorphism near a human interferon gene that is predictive of the effectiveness of an artificial interferon treatment for Hepatitis C
Individuals show different degrees of response to the various drugs used

27. The future…?

28. General idea…

29. Ethical and moral questions…
Who gets to see your genome?
Doctors?
Employers?
Insurance providers?
Government census staff
Anyone who wants?
Do you want to?
James Watson doesn’t!