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Transcript
Comparative genomics
Joachim Bargsten
February 2012
Comparative genomics
The study of the relationship of genome structure and function
across different biological species or strains.
• Why should we do this?
• How are we going to do this?
Study evolution
• Resolve
• Differences
• Mechanism
Tree of life
http://www.tolweb.org/tree/
Motivation
• Transfer knowledge from and to simpler model organisms
C. elegans
Human
Motivation
Overview
• Molecular phylogenetics
• Multiple sequence alignment
• Phylogenetic tree estimation
• Ortholog prediction
• Genome rearrangements
• Large scale inversions, deletions and translocations
• Synteny & Collinearity
• Structural variations
• Presented by Lin Ke
Molecular phylogenetics
• The use of molecular data to establish the relationship between
species, organisms or gene families
Homology
sequences that share common ancestry.
This is a all or nothing relation.
Sequences are never “a bit” homologous.
• Orthologs: homologs in different species derived by a speciation
event
• Paralogs: homologs in the same or different species derived by a
duplication event
Homology
last
common
ancestor
(co-)orthologs
Homology
last
common
ancestor
inparalogs
Homology
last
common
ancestor
outparalogs
Phylogenetic tree estimation
• How do we estimate a phylogenetic tree?
• Identify evolutionary conserved region
• Multiple sequence alignment
• MAFFT
• Estimate the phylogenetic tree
• PhyML
Phylogenetic tree estimation
• Multiple sequence alignment
Phylogenetic tree estimation
Phylogenetic tree estimation
• Infer evolutionary relationships
between species and genes/proteins
• Rooted tree
• Order of evolutionary
events
• Unrooted tree
• Evolutionary relationships
between descendants
Non-coding regions
• Phylogenetic footprinting
• Distantly related species
• Phylogenetic shadowing
• Closely related species
• Use sequence comparison and
multiple alignment to find exons
and non-coding functional regions
• E.g. Transcription factor
binding sites
What can we do with it?
• Gene annotation
• Gene or protein function prediction
• Identify non-coding elements in the genome
• Species phylogeny
• Genome evolution
Genome alignment
• Pairwise alignment
• Match chromosome sequence from species A to species B
Genome alignment – dot plot
Dot-plot chromosome 2L tomato - potato
Synteny & collinearity
• Synteny
gene loci are on the same chromosome
• Conserved synteny
gene loci are on the same chromosome in different
species
• Collinearity
The order of the gene loci is preserved across species
inverted
Resources
• Comparative genomics plants
• Plant Genome Duplication Database
• http://chibba.agtec.uga.edu/duplication/
• Plaza
• http://bioinformatics.psb.ugent.be/plaza/
Exercise
ssh –X [email protected]
cd /mnt/geninf15/work/bif_course_2012/comparative_genomics_jwb
less assignment.txt
kwrite assignment.txt