The Neurodevelopmental Gene MSANTD2 Belongs to a Gene Family Formed by Recurrent Molecular Domestication of Harbinger Transposons at the Base of Vertebrates

The formation of new genes is a major source of organism evolutionary innovation. Beyond their mutational effects, transposable elements can be co-opted by host genomes to form different types of sequences including novel genes, through a mechanism named molecular domestication. We report the formation of four genes through molecular domestication of Harbinger transposons, three in a common ancestor of jawed vertebrates about 500 million years ago and one in sarcopterygians approx. 430 million years ago. Additionally, one processed pseudogene arose approx. 60 million years ago in simians. In zebrafish, Harbinger-derived genes are expressed during early development but also in adult tissues, and predominantly co-expressed in male brain. In human, expression was detected in multiple organs, with major expression in the brain particularly during fetal development. We used CRISPR/Cas9 with direct gene knock-out in the F0 generation and the morpholino antisense oligonucleotide knock-down technique to study in zebrafish the function of one of these genes called MSANTD2, which has been suggested to be associated to neuro-developmental diseases such as autism spectrum disorders and schizophrenia in human. MSANTD2 inactivation led to developmental delays including tail and nervous system malformation at one day post fertilization. Affected embryos showed dead cell accumulation, major anatomical defects characterized by impaired brain ventricle formation and alterations in expression of some characteristic genes involved in vertebrate nervous system development. Hence, the characterization of MSANTD2 and other Harbinger-derived genes might contribute to a better understanding of the genetic innovations having driven the early evolution of the vertebrate nervous system.