In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression

Author:

Zagrijchuk Elizaveta A.1,Sabirov Marat A.1,Holloway David M.2,Spirov Alexander V.13

Affiliation:

1. Lab Modeling of Evolution, I.M. Sechenov Institute of Evolutionary Physiology & Biochemistry, Russian Academy of Sciences, Thorez Pr. 44, St.-Petersburg, 2194223, Russia

2. Mathematics Department, British Columbia Institute of Technology, 3700 Willingdon Ave. Burnaby, B.C. V5G 3H2, Canada

3. Computer Science and CEWIT, SUNY Stony Brook, Stony Brook, 1500 Stony Brook Road, Stony Brook, 11794 NY, USA

Abstract

Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes.

Publisher

World Scientific Pub Co Pte Lt

Subject

Computer Science Applications,Molecular Biology,Biochemistry

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