Distorted sex ratios: a window into RNAi-mediated silencing

Abstract

Some species ofDrosophila have unequal ratios of males to females, and now two genes--one responsible for such sex-ratio distortion and one that suppresses it--have been identified in one of these species.

Figure 1. Mechanistic and Evolutionary Model for sex-ratio Distortion

The X-linked Dox gene first evolved to target an unknown component of the Y chromosome, so that Y-bearing sperm fail to develop. This leads to an increased transmission frequency of the Dox-bearing X chromosome and a female-biased sex ratio. It remains unclear whether Dox is an RNA or protein-coding gene. Later, a transposition of Dox to Chromosome 3 created the Nmy gene. siRNAs produced from the double-stranded hairpin of Nmy target the homologous region of Dox for degradation via the RNAi pathway. As a result, Y-bearing sperm develop normally, and X-chromosome meiotic drive is suppressed. The model depicts a pre-meiotic germ cell, but the cellular manifestation of distortion occurs during nuclear condensation and maturation of sperm. Only the sex and third chromosomes are shown.

Figure 2. Two Models for the Role of Responder (Rsp) in Segregation Distortion (SD)

The Sd gene encodes a truncated RanGAP, which mislocalizes to the nucleus. (A) In a previous model [14], nuclear RanGAP binds abnormally to Rsp satellite repeats on Chromosome 2 during spermatogenesis. Chromatin condensation is disrupted in chromosomes carrying a high number of repeats (Rsp ^S), resulting in developmental failure of sperm bearing these chromosomes [16]. (B) Alternatively, SD is caused by disruption of an RNAi-dependent silencing process as suggested by Tao et al. [3]. Mislocalized RanGAP disrupts proper nuclear transport of small Rsp-derived RNAs and ribonucleoprotein (RNP) complexes that are required to repress the Rsp satellites. As a result, proper heterochromatic repression of Rsp ^S is disrupted, causing defects in chromatin condensation and loss of Rsp ^S-bearing sperm.

Figure 3. Model for the Role of RNAi in Hybrid Embryonic Lethality

Hybrid embryos produced from D. melanogaster mothers and D. simulans fathers inherit Zhr-derived rasiRNAs from the maternal cytoplasm. These small RNAs are required during the early embryonic divisions for proper silencing of the Zhr locus. In contrast, hybrid embryos from D. simulans mothers and D. melanogaster fathers do not contain maternally loaded Zhr rasiRNAs. As a result, Zhr is not silenced in hybrid females carrying the D. melanogaster X chromosome, resulting in heterochromatin decondensation and embryonic death. Hybrid male embryos from this cross do not carry the D. melanogaster X and thus are viable. We suggest that the 359-bp, 1.688-g/cm³ satellite corresponds to Zhr (see text for details).