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The  LRRC37  gene family maps to a complex region of the human genome and has been subjected to multiple rounds of segmental duplication. We investigate the expression and regulation of this gene family in multiple tissues and organisms and show a testis-specific expression of this gene family in mouse but a more ubiquitous pattern of expression among primates. Evolutionary and phylogenetic analyses support a model in which new alternative promoters have been acquired during primate evolution. We identify two promoters, Cl8 and particularly Cl3, both of which are highly active in the cerebellum and fetal brain in human and have been duplicated from a promoter region of two unrelated genes,  BPTF  and  DND1 , respectively. Two of these more broadly expressed gene family members,  LRRC37A1  and  A4 , define the boundary of a common human inversion polymorphism mapping to chromosome 17q21.31 (the  MAPT  locus)—a region associated with risk for frontal temporal dementia, Parkinsonism, and intellectual disability. We propose that the regulation of the  LRRC37  family occurred in a stepwise manner, acquiring foreign promoters from  BPTF  and  DND1  via segmental duplication. This unusual evolutionary trajectory altered the regulation of the  LRRC37  family, leading to increased expression in the fetal brain and cerebellum.

Primate segmental duplication creates novel promoters for theLRRC37gene family within the 17q21.31 inversion polymorphism region