Open AccessHuman disease locus discovery and mapping to molecular pathways through phylogenetic profiling
Author(s) -
Tabach Yuval,
Golan Tamar,
HernándezHernández Abrahan,
Messer Arielle R,
Fukuda Tomoyuki,
Kouznetsova Anna,
Liu JianGuo,
Lilienthal Ingrid,
Levy Carmit,
Ruvkun Gary
Publication year - 2013
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2013.50
Subject(s) - biology , genetics , gene , microphthalmia associated transcription factor , phylogenetic tree , locus (genetics) , phylogenetics , computational biology , genome , transcription factor , human genome , evolutionary biology
Genes with common profiles of the presence and absence in disparate genomes tend to function in the same pathway. By mapping all human genes into about 1000 clusters of genes with similar patterns of conservation across eukaryotic phylogeny, we determined that sets of genes associated with particular diseases have similar phylogenetic profiles. By focusing on those human phylogenetic gene clusters that significantly overlap some of the thousands of human gene sets defined by their coexpression or annotation to pathways or other molecular attributes, we reveal the evolutionary map that connects molecular pathways and human diseases. The other genes in the phylogenetic clusters enriched for particular known disease genes or molecular pathways identify candidate genes for roles in those same disorders and pathways. Focusing on proteins coevolved with the microphthalmia‐associated transcription factor (MITF), we identified the Notch pathway suppressor of hairless (RBP‐Jk/SuH) transcription factor, and showed that RBP‐Jk functions as an MITF cofactor.