Abstract
Heterogametic sex chromosomes have evolved independently in various lineages of vertebrates. Such sex chromosome pairs often contain nonrecombining regions, with one of the chromosomes harboring a master sex-determining (SD) gene. It is hypothesized that these sex chromosomes evolved from a pair of autosomes that diverged after acquiring the SD gene. By linkage and association mapping of the SD locus in fugu (Takifugu rubripes), we show that a SNP (C/G) in the anti-Müllerian hormone receptor type II (Amhr2) gene is the only polymorphism associated with phenotypic sex. This SNP changes an amino acid (His/Asp384) in the kinase domain. While females are homozygous (His/His384), males are heterozygous. Sex in fugu is most likely determined by a combination of the two alleles of Amhr2. Consistent with this model, the medaka hotei mutant carrying a substitution in the kinase domain of Amhr2 causes a female phenotype. The association of the Amhr2 SNP with phenotypic sex is conserved in two other species of Takifugu but not in Tetraodon. The fugu SD locus shows no sign of recombination suppression between X and Y chromosomes. Thus, fugu sex chromosomes represent an unusual example of proto–sex chromosomes. Such undifferentiated X-Y chromosomes may be more common in vertebrates than previously thought.
Highlights
Diverse systems of sex determination have evolved independently in the animal and plant kingdoms [1]
We investigated the SD locus in fugu by high-resolution genetic mapping and association mapping
We found that a SNP that changes an amino acid (His/Asp384) in the kinase domain of anti-Mullerian hormone receptor type II (Amhr2) is perfectly associated with phenotypic sex
Summary
Diverse systems of sex determination have evolved independently in the animal and plant kingdoms [1]. This implies that Amhr2D384 is a dominant allele This interpretation is consistent with the male to female sex-reversal in the medaka Amhr homozygous mutant (hotei) that has a loss-of-function mutation in the kinase domain (Tyr390Cys) [22], located 13 positions downstream of fugu Asp384 (see Figure 3C). Allelic Sex Determination by a Non-Transcription Factor In vertebrates, previously four master SD genes were known: Sry in therian mammals [4]; Dmrt in chicken [5]; Dmy in medaka [6]; and Dm-W in Xenopus laevis [7]. Since Amh/ Amhr signaling plays a role downstream of the SD gene in many vertebrates including mammals, birds and medaka [15,22,35], the fixation of such a downstream factor as the new SD locus might explain the later onset of the gonadal dimorphism, which occurs around 8–9 weeks after fertilization in fugu. The extent of the contribution of sex-reversed XY females in maintaining similarity at the SD locus of fugu is unclear
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