Medical Genomics – Lecture 5 – Comparative genomics
Comparative genomics; The genome sequences of different species are compared
Application for comparative genomics
Phylogenetic analysis
Phylogeny; the sequence of events involved in the evolutionary
development of a species or group of species
Phylogenetic tree; diagram that describes the phylogeny of a
species
Changes occurred during het evolution include single nucleotide
changes (deletion, insertions, substitution) as well as larger rearrangements
(translocation, deletions, inversions etc.).
Identification of those changes provides information about the order in which
they evolved (ontwikkelen)
Principle of parsimony; the order of speciation with the lowest number of
evolutionary changes is the most likely to have occurred. (three 3 most likely
because it requires the fewest mutations)
Homology transfer
Using sequence similarity to predict gene function. Sequence similarity
reflects functional similarity. This has to be tested.
Concept apply to;
Genes; human gene of unknown function encodes amino acid
sequence that is highly similar to a well-characterized enzyme in another
organisms. Logical to predict that the human gene has a similar enzymatic
activity.
Gene fragments (DNA fragmenten); Full-length proteins are composed of
multiple domains that act as functional units. Domains occur in many genes
and often structure-function relationship is known. Examples are ATPase
domains, DNA binding sites, transmembrane segments
Recognition of domain in amino acid sequence is easy and enables you to know the
function.
Syntenic maps
Syntheny; chromosomal rearrangements leave detectable
marks in the genome.
Chromosome segments in 2 species are synthetic if; they have
sequence similarity that is not limited to a single gene, but
many genes so that also the order of the genes on the
chromosome is conserved (behouden)
Larger evolutionary distance --> smaller syntenic fragments
Comparative genomics; The genome sequences of different species are compared
Application for comparative genomics
Phylogenetic analysis
Phylogeny; the sequence of events involved in the evolutionary
development of a species or group of species
Phylogenetic tree; diagram that describes the phylogeny of a
species
Changes occurred during het evolution include single nucleotide
changes (deletion, insertions, substitution) as well as larger rearrangements
(translocation, deletions, inversions etc.).
Identification of those changes provides information about the order in which
they evolved (ontwikkelen)
Principle of parsimony; the order of speciation with the lowest number of
evolutionary changes is the most likely to have occurred. (three 3 most likely
because it requires the fewest mutations)
Homology transfer
Using sequence similarity to predict gene function. Sequence similarity
reflects functional similarity. This has to be tested.
Concept apply to;
Genes; human gene of unknown function encodes amino acid
sequence that is highly similar to a well-characterized enzyme in another
organisms. Logical to predict that the human gene has a similar enzymatic
activity.
Gene fragments (DNA fragmenten); Full-length proteins are composed of
multiple domains that act as functional units. Domains occur in many genes
and often structure-function relationship is known. Examples are ATPase
domains, DNA binding sites, transmembrane segments
Recognition of domain in amino acid sequence is easy and enables you to know the
function.
Syntenic maps
Syntheny; chromosomal rearrangements leave detectable
marks in the genome.
Chromosome segments in 2 species are synthetic if; they have
sequence similarity that is not limited to a single gene, but
many genes so that also the order of the genes on the
chromosome is conserved (behouden)
Larger evolutionary distance --> smaller syntenic fragments
