Genome structure and evolution Wellcome （基因组结构和进化威康）.ppt

Introduction Non-coding DNA Identification Estimation Evolution (adaptation?) Expression (where? function?) Evolution of expression levels How do gene expression levels evolve over time? Is selection or drift the main factor? Collaboration with Philipp Khaitovich (Shanghai); Raphaelle Chaix (Paris) Structured Coalescent Population genetics with geographical structure (E.g. island populations; HIV transmission in different risk groups) Collaboration met Chris Holmes (Oxford), Oliver Pybus (Oxford), Alexei Drummond (New Zealand), Andrew Rambaut (Edinburgh) ABI 1100 bases / read, 1 Mb / day Roche / 454 250 bases / read, 100 Mb / 7.5 hour Solexa / Illumina 35-50 bases / read, 2 Gb / 6.5 hour 2. Genome evolution – double stranded break repair Accidental breaks are also repaired through the non-homologous end joining (NHEJ) pathway. Does not require homologous sequence. Evolutionary very old pathway: yeast and some bacterial species have NHEJ. Repairs most breaks correctly, but is also able to induce translocations (chromosome rearrangements). Gill and Fast BMC Molecular Biology 2007 8:24 ? doi:10.1186/1471-2199-8-24 2. Genome evolution – chromosomal rearrangements Mouse chromosomes (1-19 and X) coloured according to homology with human chromosomes (1-22 and X). In the about 2 x 80 million years that separate humans and mice, many chromosomal rearrangements have occurred. Sequence evolution and alignment Context dependent substitution models Indels Statistical alignment Uncertainty in Homology Inferences: Assessing and Improving Genomic Sequence Alignment Gerton Lunter, Andrea Rocco, Naila Mimouni, Andreas Heger, Alexandre Caldeira, and Jotun Hein New sequencing technologies This week Genome structure and evolution -- general introduction, biological motivation Bayesian statistics; Stochastic processes; substitutions Pairwise alignments; probabilistic alignments; hidden Markov models Applications: Neutral indel model; amount of functional se