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Background  Four ohnologous genes ( sox1 ,  sox2 ,  sox3 , and  sox15 ) were generated by two rounds of whole-genome duplication in a vertebrate ancestor. In eutherian mammals,  Sox1 ,  Sox2 , and  Sox3  participate in central nervous system (CNS) development.  Sox15  has a function in skeletal muscle regeneration and has little functional overlap with the other three ohnologs. In contrast, the frog  Xenopus laevis  and zebrafish orthologs of  sox15  as well as  sox1-3  function in CNS development. We previously reported that  Sox15  is involved in mouse placental development as neofunctionalization, but is pseudogenized in the marsupial opossum. These findings suggest that  sox15  might have evolved with divergent gene fates during vertebrate evolution. However, knowledge concerning  sox15  in other vertebrate lineages than therian mammals, anuran amphibians, and teleost fish is scarce. Our purpose in this study was to clarify the fate and molecular evolution of  sox15  during vertebrate evolution.    Results  We searched for  sox15  orthologs in all vertebrate classes from agnathans to mammals by significant sequence similarity and synteny analyses using vertebrate genome databases. Interestingly,  sox15  was independently pseudogenized at least twice during diversification of the 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 an increased  d  N / d  S  ratio for  sox15  compared to the other three ohnologs during jawed vertebrate evolution.    Conclusions  The findings revealed an asymmetric evolution of  sox15  among the four ohnologs during vertebrate evolution, which was supported by the increased  d  N / d  S  values in cartilaginous fishes, anuran amphibians, and amniotes. The increased  d  N / d  S  value of  sox15  may have been caused mainly by relaxed selection. 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.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12862-021-01864-z.

Independent pseudogenizations and losses of sox15 during amniote diversification following asymmetric ohnolog evolution