"Will the correct ORFs please stand up? tribulations of using genome data for constructing a deep phylogeny"
Wednesday, December 11, 2019 - 11:00
School of Life Sciences, MSI Small Lecture Theatre
Professor Geoff Barton FRSE FRSB
Dr Christopher Southan
University of Edinburgh
BAC1 and BACE2 are key protease targets for Alzheimer's and diabetes, respectively for which deep phylogenetic analysis has already added functional insights ("A tale of two drug targets: the evolutionary history of BACE1 and BACE2", Southan & Hancock, 2013, PMID: 24381583). However, the analysis, both back then and during updating, came up against two key problems. The first was a surprising prevalence of incorrect protein sequences predicted even from vertebrate genomic data. This is especially the case in Ensembl where many BACE1 and BACE2 orthologues have truncation and/or indel errors. The second was that some key phylogenetic representative genomes are still languishing in an unfinished state (e.g. Trichoplax adhaerens isstill the 2006 first-draft) leading to poor resolution of paralogues from fragmented assemblies. These technical challenges of incorrect ORFs, options for their amelioration and an update on the evolution of these enzymes will be outlined in this talk.