This is the first presentation of the BITS training on 'Comparative genomics'. It reviews the basic concepts of sequence homology on different levels. Thanks to Klaas Vandepoele of the PSB department.

1. Comparative genomics
in eukaryotes
Klaas Vandepoele, PhD
Klaas.Vandepoele@psb.vib-ugent.be
Professor Ghent University
Comparative & Integrative Genomics
VIB – Ghent University, Belgium
http://www.bits.vib.be

2. Outline
 Introduction
 Gene family analysis
 Genome analysis
 ConTra: promoter alignment analysis
2

3. What is comparative genomics?
 Because all modern genomes have arisen from
common ancestral genomes, the relationships
between genomes can be studies with this fact in
mind. This commonality means that information gained
in one organism can have application in other even
distantly related organisms. Comparative genomics
enables the application of information gained from
facile model systems to agricultural and medical
problems. The nature and significance of differences
between genomes also provides a powerful tool for
determining the relationship between genotype and
phenotype through comparative genomics and
morphological and physiological studies.
3 http://genomics.ucdavis.edu/what.html

4. Principles
 DNA sequences encoding and regulating the
expression of essential proteins and RNAs will be
conserved
 Consequently, the regulatory profiles of genes
involved in similar processes among related
species will be conserved
 Conversely, sequences that encode or control the
expression of proteins or RNAs responsible for
differences between species will be divergent
4

5. Definition
“ The combination of genomic data and comparative /
evolutionary biology to address questions of genome
structure, evolution and function”
5 Hardison, PLoS Biology 2003

6. What can we learn from cross-
species comparisons?
 Genome conservation
 transfer knowledge gained from model
organisms to non-model organisms
 Genome variation
 understand how genomes change over time in
order to identify evolutionary processes and
constraints
 Detection of functional elements
 Coding elements (e.g. exons)
 Conserved non-coding sequences / elements
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7. Conservation of gene structure
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8. Homology & sequence similarity
 Homology = shared ancestral common
origin
 Inferred based on:
 Sequence similarity
 Similar (multi-) protein domain
composition and organization
 So sequence similarity means homology?
 No, it depends!
8 "Orthologs, paralogs, and evolutionary genomics“, Koonin 2005

9. Homology & sequence similarity
Sequence analysis aims at finding important sequence similarities
Sequence analysis aims at finding important sequence similarities
that would allow one to infer homology. The latter term is extensively
that would allow one to infer homology. The latter term is extensively
used in scientific literature, often without a clear understanding of its
used in scientific literature, often without a clear understanding of its
meaning, which is simply common origin.
meaning, which is simply common origin.
Homologous organs are not necessarily similar (at least the similarity
Homologous organs are not necessarily similar (at least the similarity
may not be obvious); similar organs are not necessarily homologous.
may not be obvious); similar organs are not necessarily homologous.
For some reason, this simple concept tends to get extremely muddled
For some reason, this simple concept tends to get extremely muddled
when applied to protein and DNA sequences. Phrases like “sequence
when applied to protein and DNA sequences. Phrases like “sequence
(structural) homology”, “high homology”, “significant homology”,
(structural) homology”, “high homology”, “significant homology”,
or even “35% homology” are as common, even in top scientific
or even “35% homology” are as common, even in top scientific
journals, as they are absurd, considering the definition.
journals, as they are absurd, considering the definition.
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10. Multiple Sequence Alignments
Columns (~positions) in the alignment
Sequences (~taxa)
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11. Genome-wide sequence retrieval
 Finding information from whole-genome
low
sequencing projects
 DNA sequence reads
 Assembled genomic DNA sequences
Information value
 Annotated genes (RNA genes + protein-
encoding genes)
 Repeats, transposable elements
 Integrated platform providing both sequence
high
data and functional genomics data
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12. Genome databases
 Species-specific databases
 SGD
 TAIR
 Many others, e.g. wormbase, flybase,...
 General & Integrative repositories
 EBI Genomes & Integr8 / Ensembl
 NCBI Entrez Genome
 UCSC
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