Sk-2 is a meiotic drive element that was discovered in wild populations of Neurospora fungi over 40 years ago. While early studies quickly determined that Sk-2 transmits itself through sexual reproduction in a biased manner via spore killing, the genetic factors responsible for this phenomenon have remained mostly unknown. Here, we identify and characterize rfk-1, a gene required for Sk-2-based spore killing. The rfk-1 gene contains four exons, three introns, and two stop codons, the first of which undergoes RNA editing to a tryptophan codon during sexual development. Translation of an unedited rfk-1 transcript in vegetative tissue is expected to produce a 102-amino acid protein, whereas translation of an edited rfk-1 transcript in sexual tissue is expected to produce a protein with 130 amino acids. These findings indicate that unedited and edited rfk-1 transcripts exist and that these transcripts could have different roles with respect to the mechanism of meiotic drive by spore killing. Regardless of RNA editing, spore killing only succeeds if rfk-1 transcripts avoid silencing caused by a genome defense process called meiotic silencing by unpaired DNA (MSUD). We show that rfk-1's MSUD avoidance mechanism is linked to the genomic landscape surrounding the rfk-1 gene, which is located near the Sk-2 border on the right arm of chromosome III. In addition to demonstrating that the location of rfk-1 is critical to spore-killing success, our results add to accumulating evidence that MSUD helps protect Neurospora genomes from complex meiotic drive elements.
18Meiotic drive elements cause their own preferential transmission following meiosis. In 19 fungi this phenomenon takes the shape of spore killing, and in the filamentous 20 ascomycete Neurospora sitophila, the Sk-1 spore killer element is found in many 21 natural populations. In this study, we identify the gene responsible for spore killing in 22Sk-1 by generating both long and short-read genomic data and by using these data to 23 perform a genome wide association test. Through molecular dissection, we show that 24 a single 405 nucleotide long open reading frame generates a product that both acts as a 25 poison capable of killing sibling spores and as an antidote that rescues spores that 26 produce it. By phylogenetic analysis, we demonstrate that the gene is likely to have 27 been introgressed from the closely related species N. hispaniola, and we identify three 28 subclades of N. sitophila, one where Sk-1 is fixed, another where Sk-1 is absent, and a 29 third where both killer and sensitive strain are found. Finally, we show that spore 30 killing can be suppressed through an RNA interference based genome defense 31 pathway known as meiotic silencing by unpaired DNA. Spk-1 is not related to other 32 known meiotic drive genes, and similar sequences are only found within Neurospora. 33 These results shed new light on the diversity of genes capable of causing meiotic 34 drive, their origin and evolution and their interaction with the host genome. 35 36 37 Significance Statement 38In order to survive, most organisms have to deal with parasites. Such parasites can be 39 other organisms, or sometimes, selfish genes found within the host genome itself. 40While much is known about parasitic organisms, the interaction with their hosts and 41 their ability to spread within and between species, much less is known about selfish 42 genes. We here identify a novel selfish "spore killer" gene in the fungus Neurospora 43 sitophila. The gene appears to have evolved within the genus, but has entered the 44 species through hybridization and introgression. We also show that the host can 45 counteract the gene through RNA interference. These results shed new light on the 46 diversity of selfish genes in terms of origin, evolution and host interactions. 47 111 sitophila. Using whole genome sequencing of 56 N. sitophila strains we show that Sk-112 1 spore killing is caused by a single gene and demonstrate that it is responsible for 113 both killing and resistance. Our data suggests that the Sk-1 gene has been introgressed 114 from a different Neurospora species, potentially N. hispaniola. Furthermore, we show 115 that the population structure of N. sitophila is divided into three subclades, one of 116 which is fixed for Sk-1, one where Sk-1 is absent and a third where killers and 117 sensitives intermix. Finally, we show that spore killing can be suppressed in certain 118 crosses by an RNAi based genome defense mechanism known as meiotic silencing by 119 unpaired DNA (MSUD). 120 Results 121The locus responsible for spore killing i...
The pairing of homologous chromosomes represents a critical step of meiosis in nearly all sexually reproducing species. In many organisms, pairing involves chromosomes that remain apparently intact. The mechanistic nature of homology recognition at the basis of such pairing is unknown. Using “meiotic silencing by unpaired DNA” (MSUD) as a model process, we demonstrate the existence of a cardinally different approach to DNA homology recognition in meiosis. The main advantage of MSUD over other experimental systems lies in its ability to identify any relatively short DNA fragment lacking a homologous allelic partner. Here, we show that MSUD does not rely on the canonical mechanism of meiotic recombination, yet it is promoted by REC8, a conserved component of the meiotic cohesion complex. We also show that certain patterns of interspersed homology are recognized as pairable during MSUD. Such patterns need to be colinear and must contain short tracts of sequence identity spaced apart at 21 or 22 base pairs. By using these periodicity values as a guiding parameter in all-atom molecular modeling, we discover that homologous DNA molecules can pair by forming quadruplex-based contacts with an interval of 2.5 helical turns. This process requires right-handed plectonemic coiling and additional conformational changes in the intervening double-helical segments. Our results 1) reconcile genetic and biophysical evidence for the existence of direct homologous double-stranded DNA (dsDNA)–dsDNA pairing, 2) identify a role for this process in initiating RNA interference, and 3) suggest that chromosomes can be cross-matched by a precise mechanism that operates on intact dsDNA molecules.
Meiotic drive elements cause their own preferential transmission following meiosis. In fungi, this phenomenon takes the shape of spore killing, and in the filamentous ascomycete Neurospora sitophila, the Sk-1 spore killer element is found in many natural populations. In this study, we identify the gene responsible for spore killing in Sk-1 by generating both long- and short-read genomic data and by using these data to perform a genome-wide association test. We name this gene Spk-1. Through molecular dissection, we show that a single 405-nt-long open reading frame generates a product that both acts as a poison capable of killing sibling spores and as an antidote that rescues spores that produce it. By phylogenetic analysis, we demonstrate that the gene has likely been introgressed from the closely related species Neurospora hispaniola, and we identify three subclades of N. sitophila, one where Sk-1 is fixed, another where Sk-1 is absent, and a third where both killer and sensitive strain are found. Finally, we show that spore killing can be suppressed through an RNA interference-based genome defense pathway known as meiotic silencing by unpaired DNA. Spk-1 is not related to other known meiotic drive genes, and similar sequences are only found within Neurospora. These results shed light on the diversity of genes capable of causing meiotic drive, their origin and evolution, and their interaction with the host genome.
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