A new rationale for TF paralog evolution, expression and function
Gene duplications are major drivers in the evolution of biological complexity, but the forces that shape paralog evolution remain incompletely understood. RUNX transcription factor paralogs are expressed in mutually exclusive cell types, sacrificing potential robustness conferred by gene duplications without obvious gain. To elucidate this issue, we explored two RUNX-dependent developmental branch points. In both settings, RUNX paralogs differed in their functional properties, providing a rationale for selective paralog expression, and allowing us to identify paralog-specific amino acids that modulate the strength of DNA binding and gene regulatory control. Remarkably, in both paradigms examined, the non-endogenously expressed paralog was biologically more potent than the endogenously expressed paralog, increasing the generation of specialized cell types regardless of environmental conditions. These findings suggest submaximal regulatory control as a driver for transcription factor paralog evolution, a conclusion supported by the evolutionary trajectory of RUNT domain residues, which indicates selection of sequences that moderate DNA binding and gene regulatory control.
Date: 3 April 2017, 13:00 (Monday, -2nd week, Trinity 2017)
Venue: Dorothy Crowfoot Hodgkin Building, off South Parks Road OX1 3QU
Venue Details: Main Seminar Room
Speaker: Professor Matthias Merkenschlager (Lymphocyte Development Group, MRC Clinical Sciences Centre, London)
Organising department: Department of Biochemistry
Organiser: Sarah-jane Scard (Department of Biochemistry)
Organiser contact email address: head@bioch.ox.ac.uk
Host: Professor Francis Barr (Department of Biochemistry, University of Oxford )
Part of: Biochemistry Department Seminar
Booking required?: Not required
Audience: Members of the University only
Editor: Sarah-Jane Scard