scholarly journals RNA editing controls meiotic drive by a Neurospora Spore killer

2021 ◽  
Author(s):  
Nicholas A. Rhoades ◽  
Thomas M. Hammond
Keyword(s):  
Amino Acid ◽  
Rna Editing ◽  
Stop Codon ◽  
Meiotic Drive ◽  
Transmission Mechanism ◽  
Mrna Editing ◽  
Vegetative Tissue ◽  
Spore Killing ◽  
Protein Variants ◽  
Spore Killer

ABSTRACTNeurospora Sk-2 is a complex meiotic drive element that is transmitted to offspring through sexual reproduction in a biased manner. Sk-2’s biased transmission mechanism involves spore killing, and recent evidence has demonstrated that spore killing is triggered by a gene called rfk-1. However, a second gene, rsk, is also critically important for meiotic drive by spore killing because it allows offspring with an Sk-2 genotype to survive the toxic effects of rfk-1. Here, we present evidence demonstrating that rfk-1 encodes two protein variants: a 102 amino acid RFK-1A and a 130 amino acid RFK-1B, but only RFK-1B is toxic. We also show that expression of RFK-1B requires an early stop codon in rfk-1 mRNA to undergo adenosine-to-inosine (A-to-I) mRNA editing. Finally, we demonstrate that RFK-1B is toxic when expressed within vegetative tissue of Spore killer sensitive (SkS) strains, and that this vegetative toxicity can be overcome by co-expressing Sk-2’s version of RSK. Overall, our results demonstrate that Sk-2 uses RNA editing to control when its spore killer is produced, and that the primary killing and resistance functions of Sk-2 can be conferred upon an SkS strain by the transfer of only two genes.

scholarly journals Combinations of Spok genes create multiple meiotic drivers in Podospora

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Aaron A Vogan ◽  
S Lorena Ament-Velásquez ◽  
Alexandra Granger-Farbos ◽  
Jesper Svedberg ◽  
Eric Bastiaans ◽  
...  
Keyword(s):  
Gene Family ◽  
Sexual Reproduction ◽  
Phylogenetic Analyses ◽  
Natural Populations ◽  
Meiotic Drive ◽  
Kinase Domain ◽  
Podospora Anserina ◽  
Spore Killing ◽  
Different Strains ◽  
Spore Killer

Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74–167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.

scholarly journals An introgressed gene causes meiotic drive in Neurospora sitophila

2020 ◽  
Author(s):  
Jesper Svedberg ◽  
Aaron A. Vogan ◽  
Nicholas A. Rhoades ◽  
Dilini Sarmarajeewa ◽  
David J. Jacobson ◽  
...  
Keyword(s):  
Rna Interference ◽  
Natural Populations ◽  
Meiotic Drive ◽  
Host Genome ◽  
Origin And Evolution ◽  
Filamentous Ascomycete ◽  
Selfish Genes ◽  
A Genome ◽  
Spore Killing ◽  
Spore Killer

AbstractMeiotic 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. Through molecular dissection, we show that a single 405 nucleotide 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 is likely to have been introgressed from the closely related species N. 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 new light on the diversity of genes capable of causing meiotic drive, their origin and evolution and their interaction with the host genome.Significance StatementIn order to survive, most organisms have to deal with parasites. Such parasites can be other organisms, or sometimes, selfish genes found within the host genome itself. While much is known about parasitic organisms, the interaction with their hosts and their ability to spread within and between species, much less is known about selfish genes. We here identify a novel selfish “spore killer” gene in the fungus Neurospora sitophila. The gene appears to have evolved within the genus, but has entered the species through hybridization and introgression. We also show that the host can counteract the gene through RNA interference. These results shed new light on the diversity of selfish genes in terms of origin, evolution and host interactions.

scholarly journals Spore-Killing Meiotic Drive Factors in a Natural Population of the Fungus Podospora anserina

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 593-605 ◽  
Author(s):  
Marijn van der Gaag ◽  
Alfons J M Debets ◽  
Jessica Oosterhof ◽  
Marijke Slakhorst ◽  
Jessica A G M Thijssen ◽  
...  
Keyword(s):  
Linkage Group ◽  
The Netherlands ◽  
Natural Population ◽  
Local Population ◽  
Meiotic Drive ◽  
Podospora Anserina ◽  
Group Iii ◽  
Spore Killing ◽  
Different Types ◽  
Spore Killer

Abstract In fungi, meiotic drive is observed as spore killing. In the secondarily homothallic ascomycete Podospora anserina it is characterized by the abortion of two of the four spores in the ascus. We have identified seven different types of meiotic drive elements (Spore killers). Among 99 isolates from nature, six of these meiotic drive elements occurred in a local population. Spore killers comprise 23% of the natural population of P. anserina in Wageningen, The Netherlands, sampled from 1991 to 1997. One Spore-killer type was also found in a French strain dating from 1937. All other isolates found so far are sensitive to spore killing. All seven Spore killer types differ in the percentage of asci that show killing and in their mutual interactions. Interactions among Spore killer types showed either mutual resistance or dominant epistasis. Most killer elements could be assigned to linkage group III but are not tightly linked to the centromere.

scholarly journals A meiotic drive element in the maize pathogenFusarium verticillioidesis located within a 102-kb region of chromosome V

2016 ◽  
Author(s):  
Jay Pyle ◽  
Tejas Patel ◽  
Brianna Merril ◽  
Chabu Nsokoshi ◽  
Morgan McCall ◽  
...  
Keyword(s):  
Mapping Population ◽  
Fusarium Verticillioides ◽  
Meiotic Drive ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Toxic Compounds ◽  
Hypervariable Regions ◽  
Spore Killing ◽  
Spore Killer ◽  
Extra Gene

ABSTRACTFusarium verticillioidesis an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Sporekiller(SkK) that causes nearly all surviving meiotic progeny from anSkK× Spore killer-susceptible (SkS) cross to inherit theSkKallele.SkKhas been mapped to chromosome V but the genetic element responsible for meiotic drive and spore killing has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from anSkK×SkSmapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location ofSkKto a contiguous 102-kb region of chromosome V, herein referred to as theSklocus. Relative toSkSgenotypes,SkKgenotypes have one extra gene within this locus for a total of 42 genes. The additional gene inSkKgenotypes, named SKL1 forSpore Killer Locus 1, is the most highly expressed gene from theSklocus during early stages of sexual development. TheSklocus also has three hypervariable regions, the longest of which includesSKL1. The possibility thatSKL1, or another gene from theSklocus, is an essential component of meiotic drive and spore killing is discussed.

scholarly journals Identification of a genetic element required for spore killing in Neurospora

2018 ◽  
Author(s):  
Nicholas A. Rhoades ◽  
Austin M. Harvey ◽  
Dilini A. Samarajeewa ◽  
Jesper Svedberg ◽  
Aykhan Yusifov ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Meiotic Drive ◽  
Present Evidence ◽  
Partial Duplication ◽  
Genome Defense ◽  
Right Border ◽  
A Genome ◽  
Spore Killing ◽  
The Right ◽  
Spore Killer

ABSTRACTMeiotic drive elements like Spore killer-2 (Sk-2) in Neurospora are transmitted through sexual reproduction to the next generation in a biased manner. Sk-2 achieves this biased transmission through spore killing. Here, we identify rfk-1 as a gene required for the spore killing mechanism. The rfk-1 gene is associated with a 1,481 bp DNA interval (called AH36) near the right border of the 30 cM Sk-2 element, and its deletion eliminates the ability of Sk-2 to kill spores. The rfk-1 gene also appears to be sufficient for spore killing because its insertion into a non-Sk-2 isolate disrupts sexual reproduction after the initiation of meiosis. Although the complete rfk-1 transcript has yet to be defined, our data indicate that rfk-1 encodes a protein of at least 39 amino acids and that rfk-1 has evolved from a partial duplication of gene ncu07086. We also present evidence that rfk-1’s location near the right border of Sk-2 is critical for the success of spore killing. Increasing the distance of rfk-1 from the right border of Sk-2 causes it to be inactivated by a genome defense process called meiotic silencing by unpaired DNA (MSUD), adding to accumulating evidence that MSUD exists, at least in part, to protect genomes from meiotic drive.

scholarly journals An introgressed gene causes meiotic drive in Neurospora sitophila

2021 ◽  
Vol 118 (17) ◽  
pp. e2026605118
Author(s):  
Jesper Svedberg ◽  
Aaron A. Vogan ◽  
Nicholas A. Rhoades ◽  
Dilini Sarmarajeewa ◽  
David J. Jacobson ◽  
...  
Keyword(s):  
Natural Populations ◽  
Meiotic Drive ◽  
Reading Frame ◽  
Origin And Evolution ◽  
Filamentous Ascomycete ◽  
Genome Defense ◽  
Genome Wide ◽  
A Genome ◽  
Spore Killing ◽  
Spore Killer

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.

scholarly journals Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1): structure–function relationships of RNA editing and dimerization

1999 ◽  
Vol 40 (4) ◽  
pp. 623-635 ◽  
Author(s):  
Ba-Bie Teng ◽  
Scott Ochsner ◽  
Qian Zhang ◽  
Kizhake V. Soman ◽  
Paul P. Lau ◽  
...  
Keyword(s):  
Structure Function ◽  
Rna Editing ◽  
Apolipoprotein B ◽  
Mutational Analysis ◽  
Mrna Editing ◽  
Editing Enzyme

scholarly journals A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans

2021 ◽  
Author(s):  
Barbara Vona ◽  
Neda Mazaheri ◽  
Sheng-Jia Lin ◽  
Lucy A. Dunbar ◽  
Reza Maroofian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Amino Acid ◽  
Rna Splicing ◽  
Stop Codon ◽  
Missense Variant ◽  
Homozygosity Mapping ◽  
Deafness Gene ◽  
Expression Studies ◽  
Hearing Function

AbstractDeafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.

scholarly journals A rare large duplication of MLH1 identified in Lynch syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abhishek Kumar ◽  
Nagarajan Paramasivam ◽  
Obul Reddy Bandapalli ◽  
Matthias Schlesner ◽  
Tianhui Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lynch Syndrome ◽  
Splice Site ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Splice Donor Site ◽  
Laboratory Diagnostics ◽  
Mmr Genes ◽  
Base Pair Deletion ◽  
Splice Site Variant

Abstract Background The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation. Methods In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families. Results Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site. Conclusions We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.

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