Polygenic Sex Determination System in Zebrafish

Abstract

BackgroundDespite the popularity of zebrafish as a research model, its sex determination (SD) mechanism is still unknown. Most cytogenetic studies failed to find dimorphic sex chromosomes and no primary sex determining switch has been identified even though the assembly of zebrafish genome sequence is near to completion and a high resolution genetic map is available. Recent publications suggest that environmental factors within the natural range have minimal impact on sex ratios of zebrafish populations. The primary aim of this study is to find out more about how sex is determined in zebrafish.Methodology/Principal FindingsUsing classical breeding experiments, we found that sex ratios across families were wide ranging (4.8% to 97.3% males). On the other hand, repeated single pair crossings produced broods of very similar sex ratios, indicating that parental genotypes have a role in the sex ratio of the offspring. Variation among family sex ratios was reduced after selection for breeding pairs with predominantly male or female offspring, another indication that zebrafish sex is regulated genetically. Further examinations by a PCR-based “blind assay" and array comparative genomic hybridization both failed to find universal sex-linked differences between the male and female genomes. Together with the ability to increase the sex bias of lines by selective breeding, these data suggest that zebrafish is unlikely to utilize a chromosomal sex determination (CSD) system.Conclusions/SignificanceTaken together, our study suggests that zebrafish sex is genetically determined with limited, secondary influences from the environment. As we have not found any sign for CSD in the species, we propose that the zebrafish has a polygenic sex determination system.

Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes

“…Our results on sex ratio variation among, but not within, families of domesticated zebrafish corroborate previous observations from other PSD systems (48)(49)(50), namely that at normal temperatures offspring sex ratio has a genetic component with strong influence of parental genotypes (30). These data support the earlier claims that sex determination in domesticated zebrafish is polygenic (30,31,33,51).…”

“…These data support the earlier claims that sex determination in domesticated zebrafish is polygenic (30,31,33,51). Then, with the temperature experiments performed in this study, we added an additional level of complexity to this polygenic system by showing different family-by-temperature crossing reaction norms, hence demonstrating the existence of GxE interactions.…”

“…Data from most cytogenetic studies (for a review, see ref. 29) and breeding experiments (30,31) indicated the lack of sex chromosomes, pointing to PSD, whereas a hormonal sex reversal experiment (32) and restriction siteassociated DNA (RAD) mapping data from crosses involving wild-type parents pointed toward a ZZ/ZW CSD system (33,34). Eventually, comparative analysis of wild-caught and domesticated lines indicated the presence of sex chromosomes in the former and the apparent loss of the region harboring the sexdetermining gene during the domestication process in the latter (34).…”

Wild Sex in Zebrafish: Loss of the Natural Sex Determinant in Domesticated Strains

“…In the absence of germ cells (Slanchev et al 2005;Siegfried and Nusslein-Volhard 2008) and in mutants in which oocytes undergo apoptosis (Rodríguez-Marí et al 2005, 2010Rodríguez-Marí and Postlethwait 2011), gonads develop as testes and individuals become males. Remarkably, mutants that produce oocytes early and reproduce as females can transform into fertile males after oocyte depletion, showing that oocytes are necessary both for primary sex determination and for maintenance of female phenotype in adult zebrafish (Dranow et al 2013).As expected from the hypothesis that oocyte death is a major feature of zebrafish sex determination, harsh environmental conditions tend to shift sex ratios in favor of males; such factors include gamma rays, hypoxia, high density, high temperature, altered thermocycles, and poor nutrition (Walker-Durchanek 1980;Shang et al 2006;Lawrence et al 2008;Abozaid et al 2011Abozaid et al , 2012Liew et al 2012;Villamizar et al 2012). Zebrafish does not, however, have a typical environmental sex-determination (ESD) mechanism like some sauropsids for which temperature is a cue (Charnier 1966;Lang and Andrews 1994;Merchant-Larios and Diaz-Hernandez 2013;Mork et al 2014).…”

“…Repeated matings of zebrafish pairs from AB, TU (Tuebingen), and Toh strains produce consistent sex ratios, but different pairs can give quite different sex ratios (Liew et al 2012). This result is expected if zebrafish has a genetic basis for sex determination with polygenic control that differs among strains (Liew et al 2012).…”