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<p><i>FoxQ2</i> 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 <i>FoxQ2</i> sequences from 21 animal phyla. We uncover three ancient <i>FoxQ2</i> paralogs in bilaterians—<i>FoxQ2I</i>, <i>FoxQ2II</i>, and <i>FoxQ2III</i>. All three were present in the chordate ancestor, and two are retained in vertebrates, indicating a richer <i>FoxQ2</i> repertoire in vertebrates than previously recognized. To assess <i>FoxQ2</i> 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. <i>FoxQ2I</i> and <i>FoxQ2II</i> show conserved anterior expression, while <i>FoxQ2III</i> 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 <i>FoxQ2I</i> in deuterostomes. Overall, this work clarifies <i>FoxQ2</i>’s evolutionary history, identifies the endodermally expressed paralog <i>FoxQ2III</i>, and proposes that early duplication of <i>FoxQ2I/II</i> enabled subfunctionalization, driving the fast evolutionary rate of FoxQ2 sequences observed in bilaterians.</p><p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月21日

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  • Giacomo Gattoni,
  • Che-Yi Lin,
  • Joshua R. York,
  • Colin Shew,
  • Daniel Keitley,
  • Carole LaBonne,
  • Jr-Kai Yu,
  • J. Andrew Gillis,
  • Elia Benito-Gutiérrez

摘要

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.