Variation and constraint in Hox gene evolution.

Area of Science:

• Developmental Biology
• Evolutionary Genetics
• Gene Regulation

Background:

• Embryonic development genes are highly conserved despite vast body plan diversity.
• The Hox gene fushi tarazu (ftz) evolved from a homeotic gene to a pair-rule segmentation gene in Drosophila.
• ftz exhibits significant variation in expression and coding regions but persists in arthropod genomes.

Purpose of the Study:

• To investigate the mechanisms preserving the ancient regulatory gene ftz from evolutionary loss.
• To determine the essential functional domains and regulatory elements responsible for ftz retention.
• To understand how ftz acquired and maintained its conserved central nervous system (CNS) function.

Main Methods:

• Expressed Drosophila Ftz proteins with mutated motifs using a neurogenic-specific ftz cis-regulatory element (CRE) in a rescued ftz mutant background.
• Tested the functional necessity of variable motifs versus the DNA-binding homeodomain for CNS function.
• Assessed the ability of the Antennapedia homeodomain to substitute for Ftz homeodomain function in the CNS.

Main Results:

• Ftz's conserved CNS function did not depend on variable motifs involved in segmentation or homeosis.
• CNS function critically required the DNA-binding homeodomain, which is less crucial for Ftz's segmentation role.
• The Antennapedia homeodomain could substitute for Ftz homeodomain function in the Drosophila CNS.

Conclusions:

• A core CNS function is the primary driver for retaining ftz in arthropod genomes.
• Acquisition of a neurogenic CRE enabled ftz to acquire a nonredundant CNS role, differentiating it from other Hox genes.
• The modularity of CREs and protein domains facilitates the stepwise acquisition of new functions, promoting gene retention during evolution.