title: A novel sperm-delivered toxin causes late-stage embryo lethality and transmission ratio distortion in C. elegans.
abstract: The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genetic elements arise that are able to gain a transmission advantage while simultaneously imposing a fitness cost on their hosts. We previously discovered one such element in C. elegans that gains a transmission advantage through a combination of paternal-effect killing and zygotic self-rescue. Here we demonstrate that this element is composed of a sperm-delivered toxin, peel-1, and an embryo-expressed antidote, zeel-1. peel-1 and zeel-1 are located adjacent to one another in the genome and co-occur in an insertion/deletion polymorphism. peel-1 encodes a novel four-pass transmembrane protein that is expressed in sperm and delivered to the embryo via specialized, sperm-specific vesicles. In the absence of zeel-1, sperm-delivered PEEL-1 causes lethal defects in muscle and epidermal tissue at the 2-fold stage of embryogenesis. zeel-1 is expressed transiently in the embryo and encodes a novel six-pass transmembrane domain fused to a domain with sequence similarity to zyg-11, a substrate-recognition subunit of an E3 ubiquitin ligase. zeel-1 appears to have arisen recently, during an expansion of the zyg-11 family, and the transmembrane domain of zeel-1 is required and partially sufficient for antidote activity. Although PEEL-1 and ZEEL-1 normally function in embryos, these proteins can act at other stages as well. When expressed ectopically in adults, PEEL-1 kills a variety of cell types, and ectopic expression of ZEEL-1 rescues these effects. Our results demonstrate that the tight physical linkage between two novel transmembrane proteins has facilitated their co-evolution into an element capable of promoting its own transmission to the detriment of organisms carrying it.
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, New Jersey, United States of America. hsseidel@wisc.edu
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Seidel
authors.forename: Michael
authors.initials: M
authors.lastname: Ailion
authors.forename: Jialing
authors.initials: J
authors.lastname: Li
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Rockman
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development; D004817:Epidermis / Q000002:abnormalities; D005260:Female; D018628:Gene Dosage; D005804:Genes, Lethal; D008040:Genetic Linkage; D040941:Heredity; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000002:abnormalities; D015388:Organelles / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D013094:Spermatozoa / Q000378:metabolism*; D014118:Toxins, Biological / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D014118:Toxins, Biological; C568275:peel-1 protein, C elegans; C568274:zeel-1 proteins, C elegans