REVIEW: Irreducible Complexity of Hox Gene: Path to the Canonical Function of the Hox Cluster

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Milana A. Kulakova^1,a*, Georgy P. Maslakov¹, Liudmila O. Poliushkevich¹

¹Department of Embryology, Faculty of Biology, St. Petersburg State University, 199034 St. Petersburg, Russia

^* To whom correspondence should be addressed.

Received: November 19, 2023; Revised: March 22, 2024; Accepted: March 27, 2024

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The evolution of major taxa is often associated with the emergence of new gene families. In all multicellular animals except sponges and comb jellies, the genomes contain Hox genes, which are crucial regulators of development. The canonical function of Hox genes involves colinear patterning of body parts in bilateral animals. This general function is implemented through complex, precisely coordinated mechanisms, not all of which are evolutionarily conserved and fully understood. We suggest that the emergence of this regulatory complexity was preceded by a stage of cooperation between more ancient morphogenetic programs or their individual elements. Footprints of these programs may be present in modern animals to execute non-canonical Hox functions. Non-canonical functions of Hox genes are involved in maintaining terminal nerve cell specificity, autophagy, oogenesis, pre-gastrulation embryogenesis, vertical signaling, and a number of general biological processes. These functions are realized by the basic properties of homeodomain protein and could have triggered the evolution of ParaHoxozoa and Nephrozoa subsequently. Some of these non-canonical Hox functions are discussed in our review.

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KEY WORDS: homeodomain, ANTP, Hox genes, non-canonical functions of Hox genes, Metazoa, ParaHoxozoa, Nephrozoa, neurogenesis, developmental autophagy, oogenesis, vertical signaling

DOI: 10.1134/S0006297924060014

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