A maternal-effect selfish genetic element in Caenorhabditis elegans

Abstract

Selfish genetic elements spread in natural populations and have an important role in genome evolution. We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode Caenorhabditis elegans The element is made up of sup-35, a maternal-effect toxin that kills developing embryos, and pha-1, its zygotically expressed antidote. pha-1 has long been considered essential for pharynx development on the basis of its mutant phenotype, but this phenotype arises from a loss of suppression of sup-35 toxicity. Inactive copies of the sup-35/pha-1 element show high sequence divergence from active copies, and phylogenetic reconstruction suggests that they represent ancestral stages in the evolution of the element. Our results suggest that other essential genes identified by genetic screens may turn out to be components of selfish elements.

Fig 1.. A maternal-effect genetic incompatibility on Chr. III.

(A) A marker on Chr. V was introgressed from the reference strain N2 into the DL238 wild isolate. Short-read sequencing of the introgression strain revealed homozygous N2 variants on Chr. III, indicating strong selection in favor of N2 variants during the generation of this strain. (B) DL238 males were crossed to hermaphrodites carrying a null allele of the peel-1/zeel-1 element (niDf9) in an otherwise N2 background (N2 peel-1^−/−). F₁ hermaphrodites were allowed to self-fertilize (top). Alternatively, F₁ hermaphrodites (middle) or males (bottom) were backcrossed to the DL238 parental strain. Embryonic lethality was scored in the F₂ progeny as percent of unhatched eggs. Dashed grey lines indicate expected embryonic lethality under the maternal-effect toxin and zygotic antidote model (see also fig. S2). Sample sizes are shown in parentheses. Error bars indicate 95% binomial confidence intervals, calculated with the Agresti-Coull method (31) (C) Punnett square showing the expected lethality in the F₂. An interaction between a maternal toxin (black rhombus) and a zygotic antidote (white circle) results in 25% embryonic lethality in the F₂ and is compatible with the lethality observed in our crosses. (D) Embryonic lethality in the F₂ progeny of a cross between wild-type N2 hermaphrodites and DL238 males. N2 carries an active copy of peel-1/zeel-1, while DL238 carries an inactive copy. Independent segregation of two fully penetrant parental-effect incompatibilities is expected to result in 43.75% embryonic lethality. Orange and blue bars denote N2 and DL238 haplotypes, respectively.

Fig 2.. sup-35 and pha-1 encode a maternal-effect selfish genetic element.

(A) Alignment of short reads from DL238 to the N2 reference genome (top). A ~50kb region on the right arm of Chr. III selected during the introgression shows sparse alignment throughout with no read support for pha-1 and weak support for sup-35. Whole genome sequence alignment across 26 nematode species (bottom). Values are phyloP scores retrieved from the UCSC genome browser (32) (B) In our model, sup-35 is a maternally deposited toxin and pha-1 is a zygotically expressed antidote. The embryonic lethality in the F₂ of the cross between DL238 and N2 peel-1^−/− (left) was completely rescued when DL238 males were crossed to a strain carrying a sup-35(e2223) loss of function allele (center), and also when both parents carried a pha-1 transgene (right). Error bars indicate 95% binomial confidence intervals, calculated using the Agresti-Coull method (31) (C) The pharynx of a phenotypically wild-type F₂ L1 worm from a DL238 × N2 peel-1^−/−4 cross. (D) The pharynx of an F₂ L1 from the same cross as in (C) showing pharyngeal morphological defects and arrested development.

Fig 3.. The sup-35/pha-1 N2 haplotype is derived and is marked by an inversion.

(Left) A gene tree built using Bayesian inference from the coding region of Y48A6C.4 in 152 C. elegans isolates and four other Caenorhabditis species. DL238, QX1211 and ECA36 cluster together in a separate branch from all other C. elegans isolates. (Right) The synteny in the region containing the sup-35/pha-1 element, as well as three highly conserved genes in the close vicinity (hmt-1, Y48A6C.4, and Y47D3A.29) is schematically represented. (ψ) denotes alleles that are pseudogenized. The genes sup-35 and Y48A6C.4 are inverted in DL238, QX1211, and ECA36 relative to the other 149 C. elegans isolates. The gene order and orientation of hmt-1, Y48A6C.4, and Y47D3A.29 in other Caenorhabditis species suggests that the inverted haplotype is the ancestral, and that the haplotype found in 149 isolates is the derived one.