GeneticsPub Date : 2024-10-07DOI: 10.1093/genetics/iyae133
Jackson Bladen, Hyuck-Jin Nam, Nitin Phadnis
{"title":"Transformation of meiotic drive into hybrid sterility in Drosophila.","authors":"Jackson Bladen, Hyuck-Jin Nam, Nitin Phadnis","doi":"10.1093/genetics/iyae133","DOIUrl":"10.1093/genetics/iyae133","url":null,"abstract":"<p><p>Hybrid male sterility is one of the fastest evolving intrinsic reproductive barriers between recently isolated populations. A leading explanation for the evolution of hybrid male sterility involves genomic conflicts with meiotic drivers in the male germline. There are, however, few examples directly linking meiotic drive to hybrid sterility. In this study, we report that the Sex-Ratio chromosome of Drosophila pseudoobscura, which causes X-chromosome drive within the USA subspecies, causes near-complete male sterility when it is moved into the genetic background of the Bogota subspecies. In addition, we show that this new form of sterility is genetically distinct from the sterility of F1 hybrid males in crosses between USA males and Bogota females. Our observations provide a tractable study system where noncryptic drive within species is transformed into strong hybrid sterility between very young subspecies.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-10-03DOI: 10.1093/genetics/iyae158
Hongfei Ji, Dian Chen, Christopher Fang-Yen
{"title":"Automated multimodal imaging of Caenorhabditis elegans behavior in multi-well plates.","authors":"Hongfei Ji, Dian Chen, Christopher Fang-Yen","doi":"10.1093/genetics/iyae158","DOIUrl":"10.1093/genetics/iyae158","url":null,"abstract":"<p><p>Assays of behavior in model organisms play an important role in genetic screens, drug testing, and the elucidation of gene-behavior relationships. We have developed an automated, high-throughput imaging and analysis method for assaying behaviors of the nematode C. elegans. We use high-resolution optical imaging to longitudinally record the behaviors of 96 animals at a time in multi-well plates, and computer vision software to quantify the animals' locomotor activity, behavioral states, and egg laying events. To demonstrate the capabilities of our system we used it to examine the role of serotonin in C. elegans behavior. We found that egg-laying events are preceded by a period of reduced locomotion, and that this decline in movement requires serotonin signaling. In addition, we identified novel roles of serotonin receptors SER-1 and SER-7 in regulating the effects of serotonin on egg laying across roaming, dwelling, and quiescent locomotor states. Our system will be useful for performing genetic or chemical screens for modulators of behavior.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-09-30DOI: 10.1093/genetics/iyae157
Alexander Mackintosh, Derek Setter
{"title":"Genealogical asymmetry under the IM model and a two-taxon test for gene flow.","authors":"Alexander Mackintosh, Derek Setter","doi":"10.1093/genetics/iyae157","DOIUrl":"https://doi.org/10.1093/genetics/iyae157","url":null,"abstract":"<p><p>Methods for detecting gene flow between populations often rely on asymmetry in the average length of particular genealogical branches, with the ABBA-BABA test being a well known example. Currently, asymmetry-based methods cannot be applied to a pair of populations and such analyses are instead performed using model-based methods. Here we investigate genealogical asymmetry under a two-population Isolation with Migration model. We focus on genealogies where the first coalescence event is between lineages sampled from different populations, as the external branches of these genealogies have equal expected length as long as there is no post-divergence gene flow. We show that unidirectional gene flow breaks this symmetry and results in the recipient population having longer external branches. We derive expectations for the probability of this genealogical asymmetry and propose a simple statistic (Am) to detect it from genome sequence data. Am provides a two-taxon test for gene flow that only requires a single unphased diploid genome from each population, with no outgroup information. We use analytic expectations and simulations to explore how recombination, unequal effective population sizes, bidirectional gene flow and background selection influence Am and find that the statistic provides unambiguous evidence for gene flow under a continent-island history. We estimate Am for genome sequence data from Heliconius butterflies and Odocoileus deer, generating results consistent with previous model-based analyses. Our work highlights a signal of gene flow overlooked to date and provides a method that complements existing approaches for investigating the demographic history of recently diverged populations.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-09-24DOI: 10.1093/genetics/iyae155
Gaston I Jofre, Andrius J Dagilis, Victoria E Sepúlveda, Tayte Anspach, Ashutosh Singh, Anuradha Chowdhary, Daniel R Matute
{"title":"Admixture in the fungal pathogen Blastomyces.","authors":"Gaston I Jofre, Andrius J Dagilis, Victoria E Sepúlveda, Tayte Anspach, Ashutosh Singh, Anuradha Chowdhary, Daniel R Matute","doi":"10.1093/genetics/iyae155","DOIUrl":"10.1093/genetics/iyae155","url":null,"abstract":"<p><p>Blastomyces is an emerging primary fungal pathogen that affects patients worldwide. The evolutionary processes that have resulted in the current diversity in the genus remain largely unexplored. We used whole genome sequences from 99 Blastomyces isolates, including two sequenced in this study using long-read technologies, to infer the phylogenetic relationships between Blastomyces species. We find that five different methods infer five different phylogenetic trees. Additionally, we find gene tree discordance along the genome with differences in the relative phylogenetic placement of several species of Blastomyces, which we hypothesize is caused by introgression. Our results suggest the urgent need to systematically collect Blastomyces samples around the world and study the evolutionary processes that govern intra- and interspecific variation in these medically important fungi.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-09-04DOI: 10.1093/genetics/iyae123
{"title":"Correction to: Fixation times of de novo and standing beneficial variants in subdivided populations.","authors":"","doi":"10.1093/genetics/iyae123","DOIUrl":"10.1093/genetics/iyae123","url":null,"abstract":"","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-09-04DOI: 10.1093/genetics/iyae098
Jia Wen, Quan Sun, Le Huang, Lingbo Zhou, Margaret F Doyle, Lynette Ekunwe, Peter Durda, Nels C Olson, Alexander P Reiner, Yun Li, Laura M Raffield
{"title":"Gene expression and splicing QTL analysis of blood cells in African American participants from the Jackson Heart Study.","authors":"Jia Wen, Quan Sun, Le Huang, Lingbo Zhou, Margaret F Doyle, Lynette Ekunwe, Peter Durda, Nels C Olson, Alexander P Reiner, Yun Li, Laura M Raffield","doi":"10.1093/genetics/iyae098","DOIUrl":"10.1093/genetics/iyae098","url":null,"abstract":"<p><p>Most gene expression and alternative splicing quantitative trait loci (eQTL/sQTL) studies have been biased toward European ancestry individuals. Here, we performed eQTL and sQTL analyses using TOPMed whole-genome sequencing-derived genotype data and RNA-sequencing data from stored peripheral blood mononuclear cells in 1,012 African American participants from the Jackson Heart Study (JHS). At a false discovery rate of 5%, we identified 17,630 unique eQTL credible sets covering 16,538 unique genes; and 24,525 unique sQTL credible sets covering 9,605 unique genes, with lead QTL at P < 5e-8. About 24% of independent eQTLs and independent sQTLs with a minor allele frequency > 1% in JHS were rare (minor allele frequency < 0.1%), and therefore unlikely to be detected, in European ancestry individuals. Finally, we created an open database, which is freely available online, allowing fast query and bulk download of our QTL results.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-09-04DOI: 10.1093/genetics/iyae115
Thomas P Conway, Lucia Simonicova, W Scott Moye-Rowley
{"title":"Overlapping coactivator function is required for transcriptional activation by the Candida glabrata Pdr1 transcription factor.","authors":"Thomas P Conway, Lucia Simonicova, W Scott Moye-Rowley","doi":"10.1093/genetics/iyae115","DOIUrl":"10.1093/genetics/iyae115","url":null,"abstract":"<p><p>Azole resistance in the pathogenic yeast Candida glabrata is a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding gene CDR1. Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactive PDR1 alleles. While the identity of hyperactive PDR1 alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and 2 different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI/SNF complex Snf2 chromatin remodeling protein and 2 different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking either SNF2 or SPT7 exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI/SNF and SAGA exhibited a profound defect in PDR1 autoregulation, revealing that these complexes work together to ensure high-level Pdr1-dependent gene transcription.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tetraploid interspecific hybrids between Asian and African rice species restore fertility depending on killer-protector loci for hybrid sterility.","authors":"Daichi Kuniyoshi, Megumi Ishihara, Koichi Yamamori, Yohei Koide, Yuji Kishima","doi":"10.1093/genetics/iyae104","DOIUrl":"10.1093/genetics/iyae104","url":null,"abstract":"<p><p>Interspecific F1 hybrids between Asian (Oryza sativa) and African rice (Oryza glaberrima) exhibit severe sterility caused by the accumulation of hybrid sterility genes/loci at 15 or more loci. The mechanisms underlying the hybrid sterility genes are largely unknown; however, a few genes associated with the killer-protector system, which is the system most frequently associated with hybrid sterility genes, have been identified. We previously produced fertile plants as tetraploids derived from diploid interspecific F1 hybrids through anther culture; therefore, it was suggested that hybrid sterility could be overcome following tetraploidization. We investigated whether tetraploid interspecific plants produced by crossing are fertile and tested the involvement of hybrid sterility genes in the process. Fertile tetraploid interspecific F1 hybrid plants were obtained by crossing 2 tetraploids of O. sativa and O. glaberrima. To elucidate the relationships between pollen fertility and the hybrid sterility loci in the tetraploid F1 microspores, we performed genetic analyses of the tetraploid F2 hybrids and diploid plants obtained from the microspores of tetraploid interspecific hybrids by anther culture. The result suggested that the tetraploid interspecific hybrids overcame pollen and seed infertility based on the proportion of loci with the killer-protector system present in the tetraploids. The heterozygous hybrid sterility loci with the killer-protector system in the tetraploid segregate the homozygous killed allele (16.7-21.4%), with more than three-quarters of the gametes surviving. We theoretically and experimentally demonstrated that fertile rice progenies can be grown from tetraploid interspecific hybrids.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-09-04DOI: 10.1093/genetics/iyae106
Qixuan Weng, Lihong Wan, Geburah C Straker, Tom D Deegan, Bernard P Duncker, Aaron M Neiman, Ed Luk, Nancy M Hollingsworth
{"title":"An acidic loop in the forkhead-associated domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates.","authors":"Qixuan Weng, Lihong Wan, Geburah C Straker, Tom D Deegan, Bernard P Duncker, Aaron M Neiman, Ed Luk, Nancy M Hollingsworth","doi":"10.1093/genetics/iyae106","DOIUrl":"10.1093/genetics/iyae106","url":null,"abstract":"<p><p>The meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast, Saccharomyces cerevisiae. MEK1 limits resection at double-strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion, MEK1 promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover-specific pathway that enables chromosome synapsis. In addition, Mek1 phosphorylation of the meiosis-specific transcription factor, Ndt80, regulates the meiotic recombination checkpoint that prevents exit from pachytene when DSBs are present. Mek1 interacts with Ndt80 through a 5-amino acid sequence, RPSKR, located between the DNA-binding and activation domains of Ndt80. AlphaFold Multimer modeling of a fragment of Ndt80 containing the RPSKR motif and full-length Mek1 indicated that RPSKR binds to an acidic loop located in the Mek1 FHA domain, a noncanonical interaction with this motif. A second protein, the 5'-3' helicase Rrm3, similarly interacts with Mek1 through an RPAKR motif and is an in vitro substrate of Mek1. Genetic analysis using various mutants in the MEK1 acidic loop validated the AlphaFold model, in that they specifically disrupt 2-hybrid interactions with Ndt80 and Rrm3. Phenotypic analyses further showed that the acidic loop mutants are defective in the meiotic recombination checkpoint and, in certain circumstances, exhibit more severe phenotypes compared to the NDT80 mutant with the RPSKR sequence deleted, suggesting that additional, as yet unknown, substrates of Mek1 also bind to Mek1 using an RPXKR motif.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GeneticsPub Date : 2024-09-04DOI: 10.1093/genetics/iyae112
Jennifer T Krystosek, Douglas K Bishop
{"title":"Chk2 homolog Mek1 limits exonuclease 1-dependent DNA end resection during meiotic recombination in Saccharomyces cerevisiae.","authors":"Jennifer T Krystosek, Douglas K Bishop","doi":"10.1093/genetics/iyae112","DOIUrl":"10.1093/genetics/iyae112","url":null,"abstract":"<p><p>The conserved Rad2/XPG family 5'-3' exonuclease, exonuclease 1 (Exo1), plays many roles in DNA metabolism including during resolution of DNA double-strand breaks via homologous recombination. Prior studies provided evidence that the end resection activity of Exo1 is downregulated in yeast and mammals by Cdk1/2 family cyclin-dependent and checkpoint kinases, including budding yeast kinase Rad53 which functions in mitotic cells. Here, we provide evidence that the master meiotic kinase Mek1, a paralog of Rad53, limits 5'-3' single-strand resection at the sites of programmed meiotic DNA breaks. Mutational analysis suggests that the mechanism of Exo1 suppression by Mek1 differs from that of Rad53.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}