Dissecting sources of quantitative gene expression pattern divergence between Drosophila species

Area of Science:

• Developmental Biology
• Evolutionary Genomics
• Systems Biology

Background:

• Gene expression divergence between species arises from alterations in regulatory DNA or transcription factors (TFs).
• Understanding the precise mechanisms driving these expression differences is crucial for evolutionary developmental biology.

Purpose of the Study:

• To develop a modeling framework to identify the sources of gene expression divergence in Drosophila embryos.
• To investigate the regulatory circuit controlling the hunchback (hb) posterior stripe expression in three Drosophila species.

Main Methods:

• Developed a computational modeling framework to analyze gene expression patterns.
• Utilized cellular-resolution expression measurements for hb and its regulating TFs.
• Employed transgenic Drosophila melanogaster lines for experimental validation.
• Quantified TF binding site content within cis-regulatory elements (CREs).

Main Results:

• Changes in TF expression patterns significantly contribute to the divergence of hb expression between Drosophila species.
• Orthologous CREs direct largely similar, yet not identical, expression patterns across species.
• CRE sequence changes, specifically TF binding site content, correlate with altered TF sensitivity and expression divergence.

Conclusions:

• TF expression level changes are a primary driver of gene expression evolution.
• Variations in TF binding site composition within CREs influence regulatory dynamics.
• Compensatory evolution may operate in components of gene regulatory circuits beyond the cis-regulatory elements themselves.