Widespread genetic incompatibility in C. elegans maintained by balancing selection

Abstract

Natural selection is expected to eliminate genetic incompatibilities from interbreeding populations. We have discovered a globally distributed incompatibility in the primarily selfing species Caenorhabditis elegans that has been maintained despite its negative consequences for fitness. Embryos homozygous for a naturally occurring deletion of the zygotically acting gene zeel-1 arrest if their sperm parent carries an incompatible allele of a second, paternal-effect locus, peel-1. The two interacting loci are tightly linked, with incompatible alleles occurring in linkage disequilibrium in two common haplotypes. These haplotypes exhibit elevated sequence divergence, and population genetic analyses of this region indicate that natural selection is preserving both haplotypes in the population. Our data suggest that long-term maintenance of a balanced polymorphism has permitted the incompatibility to persist despite gene flow across the rest of the genome.

Fig. 1

Paternal effect-by-zygotic lethality. Percent embryonic lethality (total) was scored from crosses shown. Orange and blue indicate Bristol and Hawaii haplotypes, respectively. Pie charts show the proportions of embryos that hatched (white) and failed to hatch (black). F1 individuals were derived from reciprocal Bristol x Hawaii crosses. Embryonic lethality from selfing Bristol and Hawaii hermaphrodites, reciprocal Bristol x Hawaii, and reciprocal Bristol x F1 crosses was less than 0.8% (n > 240).

Fig. 2

zeel-1 and peel-1 map to the same 62 kb interval. A. Colored bars represent Bristol (orange) and Hawaii (blue) haplotypes carried by six RILs used to map zeel-1 and peel-1. Grey bars show regions between undetermined RIL breakpoints. RIL genotypes inferred from mapping crosses are shown to the right of the haplotypes. Red box indicates interval to which zeel-1 and peel-1 map. Gene annotations derive from WormBase (ws170) gene models for Bristol sequence. Bars indicate coverage of fosmid A (WRM0614dC06), fosmid B (WRM0633bE09), and subclones used in transgenic complementation, with rescuing transgenes in red. Asterisk indicates the frameshift introduced into the Y39G10AR.5 subclone. Arrows indicate markers used to genotype wild isolates. All markers are in complete linkage disequilibrium. B. mVista alignment of Hawaii and Bristol sequence across a portion of the zeel-1/peel-1 interval (35). We used default parameters and Bristol as the reference sequence. Black box surrounds the interval of elevated divergence between Bristol and Hawaii. Large (>50 bp) deletions (green) and insertions (grey) in Hawaii relative to the Bristol sequence are shown below the alignment.

Fig. 3

Strains compatible with Bristol and incompatible with Hawaii (orange) and strains compatible with Hawaii and incompatible with Bristol (blue) are globally distributed. Strains compatible with both Bristol and Hawaii (green) derive from a locality in Roxel, Germany. For each locality, only strains known to be genetically distinct are shown. Strain names and localities are presented in Table S7.

Fig. 4

Signature of balancing selection on the zeel-1/peel-1 interval. A. Haplotypes of 1193 base pairs of the srbc-64 gene, excluding gapped sites, are split into two deeply divergent clades, one compatible with Bristol (orange) and one with Hawaii (blue). Doubly-compatible MY19 (green) has a haplotype similar to Bristol. B. Recombination has separated the zeel-1 deletion polymorphism from marker SNPs on both sides of the divergent interval.

Fig. 5

Transgenic complementation identifies Y39G10AR.5 as zeel-1. Embryonic lethality was scored in three crosses: selfing F1 hermaphrodites carrying the transgene, Hawaii hermaphrodites x F1 males carrying the transgene, and Hawaii hermaphrodites carrying the transgene x F1 males. Orange and blue bars designate Bristol and Hawaii haplotypes, respectively. Diagonal segments represent transgenes. Within crosses, each circle represents the result for an independent transgenic line (n/d, not determined). For each result, we scored at least 50 embryos, typically 200−300. Filled circles mark results showing a significant reduction in lethality (χ² one-sided P < 0.005). Most transgenes were not integrated and were therefore not transmitted to all progeny. Arrows designate the single integrated line. In the male backcross with maternal transgene inheritance, where the integrated transgene was transmitted to all progeny, embryonic lethality was 4% (n = 298).