Genetics最新文献

{"title":"Improved sampling of genotypes and species reveals new insights on de novo gene history and regulatory origins.","authors":"Logan K Blair, Julie M Cridland, Yige Luo, David J Begun, Artyom Kopp","doi":"10.1093/genetics/iyaf074","DOIUrl":"10.1093/genetics/iyaf074","url":null,"abstract":"<p><p>The evolution of genes de novo from ancestrally nongenic sequences may be a significant mechanism of gene origin. Many studies have focused on identifying de novo genes in distant evolutionary comparisons, which bias the sample of de novo genes toward older genes that have acquired important functions and have been retained and refined by selection. In this report, we focus on the earliest steps in de novo gene origin by identifying young, polymorphic transcripts that may be missed by other study designs. To accomplish this, we sequenced tissue transcriptomes from a much larger sample of genotypes than have been used in previous analyses of de novo genes in Drosophila melanogaster. We identified 90 potential species-specific de novo genes expressed in the male accessory glands of 29 D. melanogaster lines derived from the same natural population. We find that most young transcripts are both rare in the population and transcribed at low abundance. Improved sampling of both ingroup and outgroup genotypes reveals that many young genes are polymorphic in more than 1 species, resulting in substantial uncertainty about the age and phylogenetic distribution of de novo genes. Among the genes expressed in the same tissue, gene age correlates with proximity to other tissue-specific genes, with the youngest genes being least likely to occur near established tissue-specific genes. This and other lines of evidence suggest that de novo genes do not commonly evolve by simply reutilizing preexisting regulatory elements. Together, these results provide new insights into the origin and early evolution of de novo genes.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053574","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":"Breakpoint-chiasma interference in pericentric inversion heterokaryotypes.","authors":"Øystein Kapperud","doi":"10.1093/genetics/iyaf070","DOIUrl":"10.1093/genetics/iyaf070","url":null,"abstract":"<p><p>Heterozygous inversion breakpoints inhibit the formation of chiasmata in their vicinity, and it has been suggested that they do so through the same mechanism that also causes interference between chiasmata. In this paper, I therefore extend my earlier model of chiasma interference to account for interference between breakpoints and chiasmata in pericentric inversion heterokaryotypes. Using this model to analyze recombination and sterility datasets for Drosophila melanogaster, I find support for the hypothesis that inversion breakpoints interfere with chiasmata in the same way and to the same degree that other chiasmata do. I also find that breakpoints, like chiasmata, appear to show negative interference in the pericentromeric region, and positive interference elsewhere. I discuss the implications of these findings in light of the recent HEI10 coarsening interference hypothesis, and conclude with some remarks about the evolutionary origin of chiasma interference.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023724","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}

{"title":"The proximal enhancer of the snail gene mediates negative autoregulatory feedback in Drosophila melanogaster.","authors":"Leslie Dunipace, James M McGehee, Jihyun Irizarry, Angelike Stathopoulos","doi":"10.1093/genetics/iyaf058","DOIUrl":"10.1093/genetics/iyaf058","url":null,"abstract":"<p><p>Autoregulatory feedback is a mechanism in which a gene product regulates its own expression, stabilizing gene activity amid noise and environmental changes. In Drosophila melanogaster, the gene snail encodes a key transcriptional repressor that regulates the expression of many genes during early embryogenesis, including its own expression. This study focuses on Snail occupancy at both distal and proximal enhancers of the snail gene to understand the cis-regulatory mechanisms involved in autoregulatory control. The coordinated action of these enhancers results in precisely constrained levels of snail expression during early embryogenesis. Using genome editing by CRISPR/Cas9, we found that deletion of each enhancer individually is compatible with embryonic viability under normal conditions. However, the double mutant is lethal, suggesting a functional interplay between the 2 enhancers. To gain further insight, we assayed snail gene expression levels in fixed embryos. Our results revealed that negative autoregulation of snail relies on the proximal enhancer. Moreover, increasing the affinity of binding sites for Dorsal, a transcriptional activator, in the proximal enhancer impaired this autoregulation, suggesting that Snail acts locally to counterbalance Dorsal's input. A mathematical model of snail autoregulatory control further supports our findings, reinforcing the view that the proximal enhancer mediates negative autoregulatory feedback, and implicating the distal enhancer in positive autoregulatory feedback. In summary, Snail's role at the proximal enhancer is pivotal for negative autoregulatory control and essential for balancing the activation mediated by the distal enhancer.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732679","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}

{"title":"Pairing between homologous sequences on the X and chromosome 3 in Drosophila male meiosis.","authors":"Christopher A Hylton, Katie Hansen, John E Tomkiel Dean","doi":"10.1093/genetics/iyaf059","DOIUrl":"10.1093/genetics/iyaf059","url":null,"abstract":"<p><p>Pairing between sex chromosomes in male Drosophila normally occurs at intergenic spacer (IGS) sequences within the tandemly repeated rDNA genes that are located proximally in the heterochromatin on both the X and Y. Pairing is not limited to these sequences, however, and can also occur with high fidelity between the X and segments of X euchromatin that have been translocated to the Y. Such euchromatic pairings can lead to segregation of the X and Y, even when the X is rDNA-deficient, suggesting X-Y conjunction remains at these euchromatic sequences until anaphase I. From these previous observations, however, it was unclear if conjunction occurred directly at euchromatic sequences, or if conjunction occurred due to residual IGS repeats remaining on the rDNA-deleted X. Here, to ask if pairing and conjunction of X euchromatin could occur completely independent of the rDNA, we used fluorescent in situ hybridization to examine pairing between the X chromosome and Dp(1;3) chromosomes that contain a transposed segment of the X. We found that as little as 120 kb of euchromatic homology was sufficient to ensure nearly complete pairing and could contribute to directing segregation. The ability to direct segregation was independent of the conjunction complex proteins Mod(mdg4)-in-meiosis and Teflon. We conclude that pairing can occur at X euchromatin homologies, and these interactions may persist even in the absence of the conjunction complex and contribute to segregation of the paired elements to opposite spindle poles at meiosis I.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732676","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}

{"title":"Replacement of Arabidopsis H2A.Z with human H2A.Z orthologs reveals extensive functional conservation and limited importance of the N-terminal tail sequence for Arabidopsis development.","authors":"Paja Sijacic, Dylan H Holder, Brianna D Silver, Ellen G Krall, Courtney G Willett, Maryam Foroozani, Roger B Deal","doi":"10.1093/genetics/iyaf065","DOIUrl":"10.1093/genetics/iyaf065","url":null,"abstract":"<p><p>The incorporation of histone variants, distinct paralogs of core histones, into chromatin affects all DNA-templated processes in the cell, including the regulation of transcription. In recent years, much research has been focused on H2A.Z, an evolutionarily conserved H2A variant found in all eukaryotes. In order to investigate the functional conservation of H2A.Z histones during eukaryotic evolution, we transformed h2a.z-deficient Arabidopsis thaliana plants with each of the 3 human H2A.Z variants to assess their ability to rescue the mutant defects. We discovered that human H2A.Z.1 and H2A.Z.2.1 fully complement the phenotypic abnormalities of h2a.z plants despite significant divergence in the N-terminal tail sequences of Arabidopsis and human H2A.Zs. In contrast, the brain-specific splice variant H2A.Z.2.2 has a dominant-negative effect in wild-type plants, mimicking an H2A.Z deficiency phenotype. Furthermore, human H2A.Z.1 almost completely reestablishes normal H2A.Z chromatin occupancy in h2a.z plants and restores the expression of more than 84% of misexpressed genes. Finally, we used a series of N-terminal tail truncations of Arabidopsis HTA11 to reveal that the N-terminal tail of Arabidopsis H2A.Z is not necessary for normal plant development under optimal growth conditions but does play an important role in mounting proper abiotic stress responses.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781462","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}

{"title":"Heat tolerance and genetic adaptations in Caenorhabditis briggsae: insights from comparative studies with Caenorhabditis elegans.","authors":"Nikita Jhaveri, Harvir Bhullar, Paul W Sternberg, Bhagwati P Gupta","doi":"10.1093/genetics/iyaf061","DOIUrl":"10.1093/genetics/iyaf061","url":null,"abstract":"<p><p>Temperature tolerance varies widely across species and plays a crucial role in shaping physiological and evolutionary adaptations. Here, we investigate thermal stress responses in Caenorhabditis briggsae and Caenorhabditis elegans using multiple isolates. Our results demonstrate that C. briggsae exhibits enhanced survival, growth, and reproduction at elevated temperatures compared to C. elegans. The increased heat resistance was evident from the L1 larval stage. Notably, C. briggsae isolates from both tropical and temperate regions were equally resistant to heat stress, suggesting that elevated thermal tolerance is an intrinsic feature of this species. To explore the molecular genetic basis of thermal tolerance, we examined expression of heat shock regulators. Transcriptional analysis revealed that C. briggsae mounts a rapid and robust heat shock response, with CBG19186, the closest ortholog of C. eleganshsp-16.2, showing higher induction and faster recovery dynamics. The peak expression of hsp-16.2/CBG19186 occurred at a temperature 2°C higher in C. briggsae than in C. elegans. These findings provide the first in vivo evidence of temperature differences in the transcriptional response of a single protein between the 2 species, suggesting that C. briggsae has evolved a higher thermal limit for key molecular processes, likely contributing to its ability to withstand extreme temperatures. Despite its superior thermal resistance, C. briggsae showed higher sensitivity to oxidative, osmotic, and endoplasmic reticulum stress, suggesting a potential fitness trade-off. Our findings demonstrate significant differences in stress sensitivities between the 2 nematodes, providing a foundation for further investigations into the molecular and evolutionary mechanisms underlying their stress responses.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765532","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}

{"title":"Intrinsically disordered arginine-glycine repeat domains tune sub-nucleolar compartmentalization in Caenorhabditis elegans.","authors":"Emily L Spaulding, Dustin L Updike","doi":"10.1093/genetics/iyaf067","DOIUrl":"10.1093/genetics/iyaf067","url":null,"abstract":"<p><p>Intrinsically disordered arginine-glycine (RG) repeat domains are enriched in multilayered biomolecular condensates such as the nucleolus. Caenorhabditis elegans nucleolar RG repeats are dispensable for nucleolar accumulation and instead contribute to the organization of sub-nucleolar compartments. The sufficiency of RG repeats to facilitate sub-nucleolar compartmentalization is unclear. In this study, we drive expression of full-length RG repeats in the C. elegans germline to test their ability to localize to nucleoli and organize into nucleolar sub-compartments in vivo. We find that repeats accumulate within germ cell nucleoli but do not enrich in the correct sub-compartment. Our results suggest that RG repeats may indirectly influence nucleolar organization by creating an environment favorable for sub-nucleolar compartmentalization of proteins primarily based on their function within the nucleolus.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796528","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}

{"title":"Testing for differences in polygenic scores in the presence of confounding.","authors":"Jennifer Blanc, Jeremy J Berg","doi":"10.1093/genetics/iyaf071","DOIUrl":"10.1093/genetics/iyaf071","url":null,"abstract":"<p><p>Polygenic scores have become an important tool in human genetics, enabling the prediction of individuals' phenotypes from their genotypes. Understanding how the pattern of differences in polygenic score predictions across individuals intersects with variation in ancestry can provide insights into the evolutionary forces acting on the trait in question and is important for understanding health disparities. However, because most polygenic scores are computed using effect estimates from population samples, they are susceptible to confounding by both genetic and environmental effects that are correlated with ancestry. The extent to which this confounding drives patterns in the distribution of polygenic scores depends on the patterns of population structure in both the original estimation panel and in the prediction/test panel. Here, we use theory from population and statistical genetics, together with simulations, to study the procedure of testing for an association between polygenic scores and axes of ancestry variation in the presence of confounding. We use a general model of genetic relatedness to describe how confounding in the estimation panel biases the distribution of polygenic scores in ways that depends on the degree of overlap in population structure between panels. We then show how this confounding can bias tests for associations between polygenic scores and important axes of ancestry variation in the test panel. Specifically, for any given test, there exists a single axis of population structure in the genome-wide association study (GWAS) panel that needs to be controlled for in order to protect the test. In the context of this result, we study the behavior of multiple approaches to control for stratification along this axis, including standard methods such using principal components as fixed covariates in the GWAS, linear mixed models, and a novel approach for directly estimating the axis using the test panel genotypes. Our analyses highlight the role of estimation noise in the models of population structure as a plausible source of residual confounding in polygenic score analyses.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021845","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}

{"title":"Correction to: Season-specific dominance broadly stabilizes polymorphism under symmetric and asymmetric multivoltinism.","authors":"","doi":"10.1093/genetics/iyaf080","DOIUrl":"10.1093/genetics/iyaf080","url":null,"abstract":"","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041455","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}

{"title":"Identification of regions required for allelic specificity at the cell wall remodeling allorecognition checkpoint in Neurospora crassa.","authors":"Adriana M Rico-Ramirez, N Louise Glass","doi":"10.1093/genetics/iyaf062","DOIUrl":"10.1093/genetics/iyaf062","url":null,"abstract":"<p><p>Allorecognition is the ability of organisms/cells to differentiate self from nonself. In Neurospora crassa, allorecognition systems serve as checkpoints to restrict germling/hyphal fusion between genetically incompatible strains. The cell wall remodeling (cwr) checkpoint functions after chemotrophic interactions and is triggered upon cell/hyphal contact, regulating cell wall dissolution and subsequent cell fusion. The cwr region consists of 2 linked loci, cwr-1 and cwr-2, that are under severe linkage disequilibrium. Phylogenetic analyses of N. crassa populations showed that cwr-1/cwr-2 alleles fall into 6 different haplogroups. Strains containing deletions of cwr-1 and cwr-2 fuse with previously haplogroup incompatible cells, indicating that cwr negatively regulates cell fusion. CWR-1 encodes a chitin polysaccharide monooxygenase; the polysaccharide monooxygenase (PMO) domain confers allelic specificity by interacting in trans with the predicted transmembrane protein, CWR-2, from a different haplogroup. However, catalytic activity of CWR-1 is not required for triggering a block in cell fusion. Two variable regions of CWR-1 (L2 and LC) in the PMO domain show high levels of structural variability between different haplogroups. CWR-1 chimeras containing a LC region from a different haplogroup were sufficient to trigger a cell fusion block, suggesting that the complete PMO domain structure is necessary for allorecognition. Modeling of the transmembrane protein CWR-2 revealed allelic variability in the 2 major extracellular domains (ED2/ED4). Chimeras of CWR-2 with swapped ED2 or ED4 or ED2/ED4 from different cwr-2 haplogroups also altered allelic specificity. This work identified key regions of CWR-1 and CWR-2 that contribute to allorecognition specificity, providing insight into the molecular basis of this process.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781457","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}