Hydin as the Candidate Master Sex Determination Gene in Channel Catfish (Ictalurus punctatus) and Its Epigenetic Regulation

Abstract

Sex determination is a fascinating area of research. To date, more than 20 master sex determination (SD) genes have been reported from vertebrate animals. With channel catfish (Ictalurus punctatus), much work has been conducted to determine its master SD gene, ranging from genetic linkage mapping, genome-wide association (GWA) analysis, genome sequencing, comparative genome analysis, epigenomic analysis, transcriptome analysis, and functional studies. Here in this mini review, we provide positional, expression, regulatory, and functional evidence supporting hydin (hydrocephalus-inducing protein or HYDIN axonemal central pair apparatus protein-like) as a master SD gene in channel catfish. Hydin is located within the sex determination region (SDR) within a mapped 8.9-Mb non-recombinational segment on chromosome 4 of channel catfish. It is highly expressed in genetic males, but not in genetic females. The alleles of X and Y are highly differentially methylated with the X chromosome being hypermethylated and the Y chromosome hypomethylated. The hypomethylated Y allele of hydin is expressed while the hypermethylated X allele is not expressed. Such allelic expression fits well with the XY sex determination system of channel catfish. Functional analysis using a methylation blocker, 5-aza-dC, demonstrated that demethylation, especially within the SDR, is accompanied with increased expression of hydin, which led to sex reversal of genetic females into phenotypic males. These evidences support the candidacy of hydin as a master SD gene in channel catfish. Future knockout and analysis of affected genes after hydin knockout should provide insights into how hydin functions as a master SD gene.