Female specific piRNA determines sex in silkworm

By | April 27, 2021
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Men and women differ in many obvious ways and this sexual dimorphism results from the integration of two processes: sex determination and sexual differentiation. Scientists in the field unraveled the genetic and molecular mechanisms, which determines sex and this research mostly was aimed at understanding how the genes that encode proteins act as sex determinants. In one of the amazing finds of recent times , Japanese scientists working on Bombyx mori ( silkworm) have shown that small non coding RNAs called as PIWI-interacting RNAs (piRNAs) ( Infact a single piRNA from female) plays a significant role in determination of sex of organism. . piRNAs doesnot code for a protein and are present in germ cells. PIWI-interacting RNAs (piRNAs) form a distinct class of small, 24-30 nt single stranded non-coding RNAs which are associated with the PIWI proteins, namely Piwi, Aubergine (Aub) and Argonaute 3 (AGO3) in Drosophila. The biogenesis of piRNAs  differ  from other small RNA biogenesis like micro RNAs (miRNAs) or endogenous small interfering RNAs (esiRNAs) which require Dicer dependent pathway. Studies have shown that the PIWI/piRNA complex has an evolutionary conserved role in the silencing of transposable elements (TE) in the germline of animals.

Sex determination in silkworm

Unlike Drosophila, mouse and humans, the chromosomal make-up of silkmoth is ZZ in males and ZW in females. In silkworm sex is determined by the presence or absence of a W sex chromosome . The silkworm W chromosome plays a dominant role in female determination (similar to Y chromosome in Humans), suggesting the existence of a dominant feminizing gene in this chromosome. However the exact mechanism for sex determination in lepidopterans has always eluded the scientists and so as the master gene on W chromosome, responsible for sex determination

The current hypothesis is that the presence or absence of a strong W-linked factor determines the sex of the organism. The important players in Drosophila sex determination (Sxl, Tra-2) are present in silkworm but are not functionally conserved in determining sex of the organism, except for Dsx which also sex specifically spliced in silkworm and known to play important role in sex determination in all insects including Silkworm.

Researchers from University of Tokyo Graduate School of Agricultural and Life Sciences and colleagues demonstrated that a single  PIWI-interacting RNA (piRNA) originating from female specific W chromosome, names fem  is the feminizing factor of B. mori, acting as a switch for sex determination and hence solved an eighty year old puzzle. The W chromosome is almost fully occupied by transposable element sequences and no functional protein-coding gene has been identified. The work published in reputed nature journal showed that inhibition of Fem-derived piRNA-mediated signalling in female embryos leads to the production of the male-specific splice variants of B. mori doublesex (Bmdsx), a gene which acts at the end of the sex differentiation cascade in many insects. Further, the work identifies a target for female specific piRNA on Z chromosome and named it Masc, which encodes a  CCCH-type zinc finger protein and silencing of Masc mRNA by Fem piRNA is required for the production of female-specific isoforms of Bmdsx in female embryos. In males (chromosome make up ZZ ) lacking W chromosome and hence no fem to repress Masc leading to development of embryo as male. This study for the first time shows that a single small non coding RNA is responsible for primary sex determination in the WZ system.

Reference :

Takashi Kiuchi, Hikaru Koga, Munetaka Kawamoto, Keisuke Shoji, Hiroki Sakai, Yuji Arai, Genki Ishihara, Shinpei Kawaoka, Sumio Sugano, Toru Shimada, Yutaka Suzuki, Masataka G. Suzuki, Susumu Katsuma,
“A single female-specific piRNA is the primary determiner of sex in the silkworm”,
  doi: 10.1038/nature13315.