Evolution of the Vertebrate Pax4/6 Class of Genes with Focus on Its Novel Member, the Pax10 Gene

Abstract

The members of the paired box (Pax) family regulate key developmental pathways in many metazoans as tissue-specific transcription factors. Vertebrate genomes typically possess nine Pax genes (Pax1–9), which are derived from four proto-Pax genes in the vertebrate ancestor that were later expanded through the so-called two-round (2R) whole-genome duplication. A recent study proposed that pax6a genes of a subset of teleost fishes (namely, acanthopterygians) are remnants of a paralog generated in the 2R genome duplication, to be renamed pax6.3, and reported one more group of vertebrate Pax genes (Pax6.2), most closely related to the Pax4/6 class. We propose to designate this new member Pax10 instead and reconstruct the evolutionary history of the Pax4/6/10 class with solid phylogenetic evidence. Our synteny analysis showed that Pax4, -6, and -10 originated in the 2R genome duplications early in vertebrate evolution. The phylogenetic analyses of relationships between teleost pax6a and other Pax4, -6, and -10 genes, however, do not support the proposed hypothesis of an ancient origin of the acanthopterygian pax6a genes in the 2R genome duplication. Instead, we confirmed the traditional scenario that the acanthopterygian pax6a is derived from the more recent teleost-specific genome duplication. Notably, Pax6 is present in all vertebrates surveyed to date, whereas Pax4 and -10 were lost multiple times in independent vertebrate lineages, likely because of their restricted expression patterns: Among Pax6-positive domains, Pax10 has retained expression in the adult retina alone, which we documented through in situ hybridization and quantitative reverse transcription polymerase chain reaction experiments on zebrafish, Xenopus, and anole lizard.

The axolotl genome and the evolution of key tissue formation regulators

“…However, we noted that certain members of the paired box family of transcription factors, which have diverse roles in tissue formation, were not found in the assembly. Consistent with the absence of Pax4 in amphibians and other vertebrate lineages 17 , the axolotl genome does not contain Pax4 but does contain Pax10. Notably, despite the presence of the Pax3 and Pax7 paralogues in all other known vertebrate lineages, we were able to identify Pax7 but not Pax3 in the axolotl genome assembly (Extended Data Fig.…”

Lizards possess the most complete tetrapod Hox gene repertoire despite pervasive structural changes in Hox clusters

“…Other loss‐prone genes have been shown to retain only limited developmental roles, or assume novel, lineage‐specific functions, while paralogs assume canonical developmental roles (e.g. Pax6 , “master regulator” of eye development, is never lost, while Pax10 and ‐4 are loss‐prone and assume marginal developmental roles; Feiner, Meyer, & Kuraku, ; Manousaki, Feiner, Begemann, Meyer, & Kuraku, ). This reasoning is often used to explain the dispensability of loss‐prone genes.…”

Reconstructing the ancestral vertebrate brain

“…Interestingly, despite finding the expression of different rhombic lip markers in the lamprey, such as Ptf1a , Wnt1 , and Atoh1 , in the dorsal hindbrain, neither Pax6 nor a very recently identified second Pax6 paralogue, Pax6B (Feiner et al . ), were expressed in a similar manner to gnathostomes. Lamprey Pax6B was indeed expressed in a deeper layer of the rhombic lip and overlapped with Ptf1a expression, unlike in the hagfish and gnathostomes (Fig.…”