Isolation of dominant XO-feminizing mutations in Caenorhabditis elegans: new regulatory tra alleles and an X chromosome duplication with implications for primary sex determination.

Abstract

A strain of Caenorhabditis elegans was constructed that permits selection of dominant or sex-linked mutations that transform XO animals (normally male) into fertile females, using a feminizing mutation, tra-2(e2046gf), which by itself does not sexually transform XO males. Twenty-three mutations were isolated after chemical mutagenesis and found to fall into both expected classes (four dominant tra-1 mutations and eight recessive xol-1 mutations) and novel classes. The novel mutations include 10 second-site mutations of tra-2, which are called eg mutations, for enhanced gain-of-function. The tra-2(gf, eg) alleles lead to complete dominant transformation of XO animals from fertile male into fertile female. Also isolated was a duplication of the left end of the X chromosome, eDp26, which has dominant XO lethal and feminizing properties, unlike all previously isolated duplications of the X chromosome. The properties of eDp26 indicate that it carries copies of one or more numerator elements, which act as part of the primary sex-determination signal, the X:A ratio. The eDp26 duplication is attached to the left tip of the X chromosome in inverted orientation and consequently can be used to generate unstable attached-X chromosomes.

Mechanisms of sex determination and X-chromosome dosage compensation

“…Initial evidence for XSEs came from the identification of relatively large X-chromosome duplications derived from the left end of X that caused XO-specific lethality ( Akerib and Meyer 1994 ; Hodgkin et al 1994 ; Hodgkin and Albertson 1995 ). The lethality was suppressed by mutations in sdc-2 .…”