Bioinformatický seminár

Tue 6 Nov. 2012, 17:20
I-9

Title: Giltae Song et al. (2012) Revealing mammalian evolutionary relationships by comparative analysis of gene clusters
Speaker: Martin Višňovec

Many software tools for comparative analysis of genomic sequence data have been
released in recent decades. Despite this, it remains challenging to determine
evolutionary relationships in gene clusters due to their complex histories
involving duplications, deletions, inversions, and conversions. One concept
describing these relationships is orthology. Orthologs derive from a common
ancestor by speciation, in contrast to paralogs, which derive from duplication.
Discriminating orthologs from paralogs is a necessary step in most multispecies
sequence analyses, but doing so accurately is impeded by the occurrence of gene
conversion events. We propose a refined method of orthology assignment based on
two paradigms for interpreting its definition: by genomic context or by sequence 
content. X-orthology (based on context) traces orthology resulting from
speciation and duplication only, while N-orthology (based on content) includes
the influence of conversion events. We developed a computational method for
automatically mapping both types of orthology on a per-nucleotide basis in gene
cluster regions studied by comparative sequencing, and we make this mapping
accessible by visualizing the output. All of these steps are incorporated into
our newly extended CHAP 2 package. We evaluate our method using both simulated
data and real gene clusters (including the well-characterized alpha-globin and
beta-globin clusters). We also illustrate use of CHAP 2 by analyzing four more
loci: CCL (chemokine ligand), IFN (interferon), CYP2abf (part of cytochrome P450 
family 2), and KIR (killer cell immunoglobulin-like receptors). These new methods
facilitate and extend our understanding of evolution at these and other loci by
adding automated accurate evolutionary inference to the biologist's toolkit. The 
CHAP 2 package is freely available from http://www.bx.psu.edu/miller_lab.