In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression.
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.
Lab Modeling of Evolution, I.M. Sechenov Institute of Evolutionary Physiology & Biochemistry, Russian Academy of Sciences, Thorez Pr. 44, St.-Petersburg, 2194223, Russia.
Elizaveta A
EA
Zagrijchuk
Marat A
MA
Sabirov
David M
DM
Holloway
Alexander V
AV
Spirov
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008969:Molecular Sequence Data; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C061245:hb protein, Drosophila