# Evolutionary dynamics of FoxQ2 transcription factors across metazoans reveals three ancient paralogs

## TL;DR

This study reveals the evolutionary history of FoxQ2 transcription factors, identifying three ancient paralogs and their distinct expression patterns in different animal groups.

## Contribution

The discovery of three ancient FoxQ2 paralogs and their distinct expression patterns in chordates provides new insights into their evolutionary dynamics and functional diversification.

## Key findings

- Three ancient FoxQ2 paralogs (FoxQ2I, FoxQ2II, FoxQ2III) were identified in bilaterians.
- FoxQ2I and FoxQ2II show conserved anterior expression, while FoxQ2III is expressed in the gut endoderm of chordates.
- Early duplication of FoxQ2I/II is proposed to have enabled subfunctionalization and accelerated evolutionary rates.

## Abstract

FoxQ2 is a highly conserved Forkhead-box transcription factor expressed anteriorly in cnidarians and bilaterians, yet its evolution is marked by rapid divergence and lineage-specific duplications or losses. Moreover, its presence and localization in vertebrate groups remains unclear. To reconcile these conflicting reports of conservation and divergence, we combine phylogenetic and synteny analyses of FoxQ2 sequences from 21 animal phyla. We uncover three ancient FoxQ2 paralogs in bilaterians—FoxQ2I, FoxQ2II, and FoxQ2III. All three were present in the chordate ancestor, and two are retained in vertebrates, indicating a richer FoxQ2 repertoire in vertebrates than previously recognized. To assess FoxQ2 expression, we analyzed mollusk, acoel, amphioxus, and zebrafish single-cell transcriptomic datasets, and conducted fluorescent in situ hybridization in amphioxus, lamprey, skate, zebrafish, and chicken. FoxQ2I and FoxQ2II show conserved anterior expression, while FoxQ2III is expressed in the gut endoderm in chordates, including amphioxus, lamprey, and skate. We also predict conserved transcription factor binding sites across amphioxus genera, revealing stage- and cell-type-specific regulatory interactions for FoxQ2I in deuterostomes. Overall, this work clarifies FoxQ2’s evolutionary history, identifies the endodermally expressed paralog FoxQ2III, and proposes that early duplication of FoxQ2I/II enabled subfunctionalization, driving the fast evolutionary rate of FoxQ2 sequences observed in bilaterians.

Phylogenetic and molecular analyses uncover three ancient FoxQ2 paralogs: FoxQ2I/II with conserved roles in anterior ectoderm specification, and FoxQ2III showing unexpected expression in specialized regions of the chordate endoderm.