August 10, 2012

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(Left) A schematic representation of the sex chromosomes of fugu. A SNP associated with phenotypic sex is located in the Amhr2 gene. (Right) Wild fugu. This study utilized genetic diversity in natural populations of fugu. © Naoki Mizuno

Assistant Professor Kiyoshi Kikuchi and his group at the University of Tokyo’s Fisheries Laboratory have identified a single nucleotide polymorphism (SNP, pronounced “snip”) that is most likely to determine the sex of fugu (the tiger pufferfish). An SNP is a single base alteration in DNA, for example the difference between the sequences AAGC and AATC.

In vertebrates, only four master sex-determining (SD) genes, Sry, Dmrt1, Dmy, and Dm-W, had been identified by the end of 2011. These genes code for transcription factors and are located on only one of the sex chromosomes surrounded by non-recombining regions. It is hypothesized that these sex chromosomes evolved from a pair of homologous chromosomes that diverged after acquiring the SD gene. However, there is no case that shows the inception of the diversification.

Fugu is the first fish whose genome has been sequenced. Dr. Kikuchi and his colleagues took full advantage of available fugu genome resources and investigated the SD locus in fugu by high-resolution genetic mapping and association mapping. They 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. There are no other polymorphic sites perfectly correlated with phenotypic sex. Thus the SNP (homozygous females and heterozygous males) is likely to be responsible for sex determination in fugu. Furthermore, they showed that fugu Amhr2 lies in a region where the recombination between X and Y chromosome still occurs. This result shows that the fugu sex chromosomes represent the first known example of a pre-differentiated phase in the development of sex chromosomes.

Paper information

Takashi Kamiya, Wataru Kai, Satoshi Tasumi, Ayumi Oka, Takayoshi Matsunaga, Naoki Mizuno, Masashi Fujita, Hiroaki Suetake, Shigenori Suzuki, Sho Hosoya, Sumanty Tohari, Sydney Brenner, Toshiaki Miyadai, Byrappa Venkatesh, Yuzuru Suzuki, Kiyoshi Kikuchi, "A Trans-Species Missense SNP in Amhr2 Is Associated with Sex Determination in the Tiger Pufferfish, Takifugu rubripes (Fugu)," PLoS Genetics 8 2012: e1002798, doi: 10.1371/journal.pgen.1002798