Abstract
Background: Four ohnologous genes (sox1, sox2, sox3, and sox15) were generated by two rounds of wholegenome duplication in a vertebrate ancestor. In eutherian mammals, Sox1, Sox2, and Sox3 participate in central nervous system (CNS) development. Sox15 functions in skeletal muscle regeneration, and has little functional overlap with the other three ohnologs. In contrast, Xenopus frog and zebrafish orthologs of sox15 as well as sox1-3s are expressed and function in CNS development. We previously reported that Sox15 is involved in mouse placental development as neofunctionalization, but is pseudogenized in marsupial opossum. These findings suggest that sox15 might have evolved with unusual gene fates during vertebrate evolution. However, knowledge concerning sox15 in other vertebrate lineages is scant. Our purpose was to clarify the fate and molecular evolution of sox15 during vertebrate evolution.Results: We searched for sox15 orthologs in various vertebrate lineages by homology and synteny analyses using vertebrate genome databases. Interestingly, sox15 was independently pseudogenized at least twice during species diversity in marsupial mammals. Moreover, we observed independent gene loss of sox15 at least twice during reptile evolution in squamates and crocodile-bird diversification. Codon-based phylogenetic tree and selective analyses revealed the highest dN/dS value for sox15 among the four ohnologs during jawed vertebrate evolution. The finding was supported by the high values in cartilaginous fishes, anuran amphibians, and amniotes. The high dN/dS value of sox15 may have been mainly caused by a relaxed selection. Marsupial and squamate sox15 may have evolved under more relaxed selection than those of eutherian mammals and testudine reptiles, respectively. Conclusions: The findings revealed an asymmetric evolution of sox15 among the four ohnologs during vertebrate evolution. Notably, independent pseudogenizations and losses of sox15 were observed during marsupial and reptile evolution, respectively. Both might have been caused by strong relaxed selection. The drastic gene fates of sox15, including neofunctionalization and pseudogenizations/losses during amniote diversification, might be caused by a release from evolutionary constraints. We discuss why sox15 has evolved under relaxed selection, considering the possible escapes from some constraints there could have been during its molecular evolution.