Course: Inferring Positive Selection (from Sequences)

Lectures

1. To come
2. Frequency spectrum (Tajima, Fu and Li, etc.)
3. Codon models (Goldman, Yang and Nielsen)
4. Polymorphism and divergence (HKA and MK tests, branch and branch-sites models)

Exercises

1. Exercise 1: Getting in touch with the Wright-Fisher model
2. Exercise 2: Tests based on the frequency spectrum
3. Exercise 3: Nei and Gojobori
4. Exercise 4: Codon models
5. Exercise 5: Polymorphism and divergence

Required files:

• Diversity.plx
• AllDiversity.plx
• NeiGojobori.plx
• AllNeiGojobori.plx
• NeiGojoboriData.plx
• NeiGojoboriDataWindow.plx
• MCcodon.dat
• MCcodonMulti.dat
• MCcodonMultiEqual.dat
• Codon models (several files in subdirectories)
• codeml.ctl (PAML control file)

Datasets:

• LysM Mg1
• LysM Mg3
• Adh Dm
• Adh Ds
• Adh Dy
• Lysozyme (small): sequences
• Lysozyme (small): tree
• Lysozyme (large): sequences
• Lysozyme (large): tree

Software

• Hudson's MS program (to be compiled)
• Seq-Gen (to be compiled)
• PAML (executables or source code)
• Seaview (executables)
• Perl and BioPerl
• R
• Rstudio (optional)
• MK test online

Articles

Articles to be discussed:

• Tajima F. (1989). Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics, 123:585-595
• Nei M. and Gojobori T. (1986). Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol. biol. Evol. 3(5):418-426.
• Duret L. (2008). Neutral theory: the null hypothesis of molecular evolution. Nature Education 1(1):218.
• Hey J. (1999). The neutralist, the fly and the selectionist. TREE 14(1):35-38

Second session:

• McDonald J. and Kreitman M. (1991). Adaptive protein evolution at the Adh locus in Drosophila. Nature 351:652-654
• Kosiol C. et al. (2008). Patterns of positive selection in six mammalian genomes. PLOS Genetics, 4(8):e1000144
• Petersen L. et al. (2007). Genes under positive selection in Escherichia coli. Genome Research. 17(9):1336-43.
• Markova-Raina P. and Petrov D. (2011). High sensitivity to aligner and high rate of false positives in the estimates of positive selection in the 12 Drosophila genomes. Genome Research 21:863-874.
• Anisimova M., Nielsen R. and Yang Z. (2003). Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites. Genetics 164(3):1229-36 (Optional)

Datasets to analyze

• SRK. Gene involve in brassicacea autoincompatibility. Two data sets are provided, for distinct species. In both cases, genomic segments contianing the locus are porivded, as well as the sub-region corresponding to the coding sequence (exons).
• FOXP2. The FOXP2 gene sequences in several humans and other Primates. A large genomic region containing the locus is also available for human.
• YeeU and YeeV. A toxin-antitoxin pair of genes in E. coli and relatives.
• Adh and Adh-related. More Adh and Adh-related genes from several species of Drosophila.

Helper tools:

• fasta2phylip.plx. Run using perl fasta2phylip.plx input.fasta output.phy