⚙
AI-generated deep summary
by claude@2026-06, 2026-06-24
· read from full text
ⓘ
This study investigated the evolutionary history and cross-species orthology of a regeneration-associated Kazald gene in axolotl, using extensive molecular phylogeny across vertebrates, synteny comparisons, and vertebrate-wide RNA-seq expression data (validated in whole tissues of axolotl, zebrafish, and sharks). The authors used phylogenetic inference to identify the regeneration-associated axolotl gene as Kazald2 and found an undescribed four-member Kazald gene family that originated after the ancestral two-rounds whole genome duplication in jawed vertebrates. They report conserved expression linkages across jawed vertebrates, with Kazald1 associated with skeletogenesis and odontogenesis and Kazald2 with regeneration, while also proposing lineage-specific innovations such as Kazald3 in teleost fish skeletogenesis and Kazald4 in avian brains, with the caveat that orthology and gene-function inference across species can be complicated by annotation issues. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Salamanders are known for their incredible regenerative abilities, but translating findings to mammals is complicated by unannotated genes and unclear orthology. An example highlighting this difficulty was a discovery in the axolotl ( Ambystoma mexicanum ) of a regeneration-associated gene that has been identified as either Kazald1 or Kazald2 . Since orthology inference of genes across species is crucial to identifying gains and losses of gene functions, and thus if gene usage is likely to be consistent across species, we investigated the evolution of the axolotl genes using an extensive cross-species analysis. Molecular phylogeny inference conclusively identified the regeneration-associated gene as Kazald2 , but also revealed an undescribed four-member Kazald gene family in jawed vertebrates. Moreover, synteny comparisons demonstrated that this family originated in the ancestral two-rounds of whole genome duplication. Additionally, we performed vertebrate-wide comparisons of Kazald gene expression profiles, employing available RNA-Seq which we validated in whole tissues of axolotl, zebrafish, and sharks. This uncovered seemingly ancestral connections conserved over jawed vertebrate evolution, such as Kazald1 with skeletogenesis and odontogenesis and Kazald2 with regeneration. It also suggested novel putative roles within specific lineages, including Kazald3 in teleost fish skeletogenesis and Kazald4 within avian brains. Our study thus demonstrates the establishment of a Kazald gene quartet in the jawed vertebrate ancestor, and elucidates the asymmetry of gene fates of its members, including deeply ancestral roles and comparably recent innovations. This provides a comprehensive report of this formerly undescribed gene family, offering a solid foundation for future studies of these genes in diverse species.
Full text
1,988 characters
· extracted from
oa-doi-fallback
· click to expand
Abstract
Salamanders are known for their incredible regenerative abilities, but translating findings to mammals is complicated by unannotated genes and unclear orthology. An example highlighting this difficulty was a discovery in the axolotl (Ambystoma mexicanum) of a regeneration-associated gene that has been identified as either Kazald1 or Kazald2. Since orthology inference of genes across species is crucial to identifying gains and losses of gene functions, and thus if gene usage is likely to be consistent across species, we investigated the evolution of the axolotl genes using an extensive cross-species analysis. Molecular phylogeny inference conclusively identified the regeneration-associated gene as Kazald2, but also revealed an undescribed four-member Kazald gene family in jawed vertebrates. Moreover, synteny comparisons demonstrated that this family originated in the ancestral two-rounds of whole genome duplication. Additionally, we performed vertebrate-wide comparisons of Kazald gene expression profiles, employing available RNA-Seq which we validated in whole tissues of axolotl, zebrafish, and sharks. This uncovered seemingly ancestral connections conserved over jawed vertebrate evolution, such as Kazald1 with skeletogenesis and odontogenesis and Kazald2 with regeneration. It also suggested novel putative roles within specific lineages, including Kazald3 in teleost fish skeletogenesis and Kazald4 within avian brains. Our study thus demonstrates the establishment of a Kazald gene quartet in the jawed vertebrate ancestor, and elucidates the asymmetry of gene fates of its members, including deeply ancestral roles and comparably recent innovations. This provides a comprehensive report of this formerly undescribed gene family, offering a solid foundation for future studies of these genes in diverse species.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵† The author died prior to the submission of this paper.
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.