Comparative genomicsJoachim 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 lifehttp://www.tolweb.org/tree/

Motivation

• Transfer knowledge from and to simpler model organisms

Human

C. elegans

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

(co-)orthologs

lastcommonancestor

Homology

inparalogs

lastcommonancestor

Homology

outparalogs

lastcommonancestor

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 relationshipsbetween 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 andmultiple alignment to find exonsand non-coding functional regions

• E.g. Transcription factorbinding 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

• Syntenygene loci are on the same chromosome

• Conserved syntenygene loci are on the same chromosome in different species

• CollinearityThe 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 USERNAME@137.224.100.212

cd /mnt/geninf15/work/bif_course_2012/comparative_genomics_jwb

less assignment.txt

kwrite assignment.txt