Pub Date : 2025-04-19DOI: 10.1038/s41437-025-00761-1
Sara Covarrubias, Carla Gutiérrez-Rodríguez, Clementina González
Tropical dry forests (TDF) are among the ecosystems with the highest deforestation and transformation rates. Because of habitat loss and fragmentation, modified landscapes can impose resistance to the movement of individuals, with important genetic consequences. One of the most affected taxa due to habitat alteration are amphibians, which currently face extreme population declines globally. Here, we used single nucleotide polymorphisms (SNPs) to evaluate genetic diversity, genetic structure, and the effect of landscape elements on genetic connectivity of the Mexican tree frog (Agalychnis dacnicolor) in a TDF biodiversity hotspot in Mexico. We collected samples of 96 individuals from 16 sites located within fragmented areas of TDF and within continuous forest in the Chamela-Cuixmala region. Sampling sites from the fragmented forest showed slightly lower genetic diversity and effective population size compared to those in the continuous forest. We detected three admixed genetic groups, in which most of the sites within the fragmented forest were differentiated from the sites within continuous forest. Although these analyses suggest historical gene flow, we did not detect significant recent migration among the three genetic groups. While original vegetation (TDF + tropical evergreen forest), and in some areas, agriculture facilitated genetic connectivity, open-areas (grasslands + human settlements + exposed soil), and agriculture in other areas limited genetic connectivity in A. dacnicolor. This study helps to understand the factors shaping contemporary population divergence in highly modified complex landscapes, and highlights the importance to maintain connectivity in a rapidly changing ecosystem.
{"title":"Recent habitat modification of a tropical dry forest hotspot drives population genetic divergence in the Mexican leaf frog: a landscape genetics approach","authors":"Sara Covarrubias, Carla Gutiérrez-Rodríguez, Clementina González","doi":"10.1038/s41437-025-00761-1","DOIUrl":"10.1038/s41437-025-00761-1","url":null,"abstract":"Tropical dry forests (TDF) are among the ecosystems with the highest deforestation and transformation rates. Because of habitat loss and fragmentation, modified landscapes can impose resistance to the movement of individuals, with important genetic consequences. One of the most affected taxa due to habitat alteration are amphibians, which currently face extreme population declines globally. Here, we used single nucleotide polymorphisms (SNPs) to evaluate genetic diversity, genetic structure, and the effect of landscape elements on genetic connectivity of the Mexican tree frog (Agalychnis dacnicolor) in a TDF biodiversity hotspot in Mexico. We collected samples of 96 individuals from 16 sites located within fragmented areas of TDF and within continuous forest in the Chamela-Cuixmala region. Sampling sites from the fragmented forest showed slightly lower genetic diversity and effective population size compared to those in the continuous forest. We detected three admixed genetic groups, in which most of the sites within the fragmented forest were differentiated from the sites within continuous forest. Although these analyses suggest historical gene flow, we did not detect significant recent migration among the three genetic groups. While original vegetation (TDF + tropical evergreen forest), and in some areas, agriculture facilitated genetic connectivity, open-areas (grasslands + human settlements + exposed soil), and agriculture in other areas limited genetic connectivity in A. dacnicolor. This study helps to understand the factors shaping contemporary population divergence in highly modified complex landscapes, and highlights the importance to maintain connectivity in a rapidly changing ecosystem.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 5","pages":"306-320"},"PeriodicalIF":3.1,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-12DOI: 10.1038/s41437-025-00760-2
Ben J. Wiens, Lucas H. DeCicco, Jocelyn P. Colella
Hybridization provides a window into the speciation process and reshuffles parental alleles to produce novel recombinant genotypes. Presence or absence of specific hybrid classes across a hybrid zone can provide support for various modes of reproductive isolation. Early generation hybrid classes can be distinguished by their combination of hybrid index and interclass heterozygosity, which can be estimated with molecular data. Hybrid index and interclass heterozygosity are routinely calculated for studies of hybrid zones, but available resources for next-generation sequencing datasets are computationally demanding and tools for visualizing triangle plots are lacking. Here, we provide a resource for identifying ancestry-informative markers (AIMs) from single nucleotide polymorphism (SNP) datasets, calculating hybrid index and interclass heterozygosity, and visualizing the relationship as a triangle plot. Our methods are implemented in the R package triangulaR. We validate our methods on an empirical dataset and simulations of genetic data from a hybrid zone between two parental groups at low, medium, and high levels of divergence. triangulaR provides accurate and precise estimates of hybrid index and interclass heterozygosity with sample sizes as low as five individuals per parental group, and similar levels of error as another program for hybrid index and interclass heterozygosity estimation, bgchm. We explore various allele frequency difference thresholds for AIM identification, and how this threshold influences the accuracy and precision of hybrid index and interclass heterozygosity estimates. We contextualize interpretation of triangle plots by describing theoretical expectations under Hardy-Weinberg Equilibrium and provide recommendations for best practices for identifying AIMs and building triangle plots.
{"title":"triangulaR: an R package for identifying AIMs and building triangle plots using SNP data from hybrid zones","authors":"Ben J. Wiens, Lucas H. DeCicco, Jocelyn P. Colella","doi":"10.1038/s41437-025-00760-2","DOIUrl":"10.1038/s41437-025-00760-2","url":null,"abstract":"Hybridization provides a window into the speciation process and reshuffles parental alleles to produce novel recombinant genotypes. Presence or absence of specific hybrid classes across a hybrid zone can provide support for various modes of reproductive isolation. Early generation hybrid classes can be distinguished by their combination of hybrid index and interclass heterozygosity, which can be estimated with molecular data. Hybrid index and interclass heterozygosity are routinely calculated for studies of hybrid zones, but available resources for next-generation sequencing datasets are computationally demanding and tools for visualizing triangle plots are lacking. Here, we provide a resource for identifying ancestry-informative markers (AIMs) from single nucleotide polymorphism (SNP) datasets, calculating hybrid index and interclass heterozygosity, and visualizing the relationship as a triangle plot. Our methods are implemented in the R package triangulaR. We validate our methods on an empirical dataset and simulations of genetic data from a hybrid zone between two parental groups at low, medium, and high levels of divergence. triangulaR provides accurate and precise estimates of hybrid index and interclass heterozygosity with sample sizes as low as five individuals per parental group, and similar levels of error as another program for hybrid index and interclass heterozygosity estimation, bgchm. We explore various allele frequency difference thresholds for AIM identification, and how this threshold influences the accuracy and precision of hybrid index and interclass heterozygosity estimates. We contextualize interpretation of triangle plots by describing theoretical expectations under Hardy-Weinberg Equilibrium and provide recommendations for best practices for identifying AIMs and building triangle plots.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 5","pages":"251-262"},"PeriodicalIF":3.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41437-025-00760-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-27DOI: 10.1038/s41437-024-00739-5
Jinliang Wang
EMIBD9 is a computer programme implementing two likelihood methods for estimating the 9 condensed IBD coefficients, Δ = {Δ1, Δ2, …, Δ9}, between a pair of individuals from their genotype data. Inbreeding coefficients of and relatedness (or kinship coefficient) between individuals are then calculated from the estimated Δ. One method is designed to apply to a small sample or a sample containing a high proportion of close relatives where allele frequencies and their powers or products are poorly estimated by assuming a large sample of non-inbred and unrelated individuals. It adopts an expectation maximisation (EM) algorithm to estimate both Δ and allele frequencies jointly and iteratively. The other method is designed to apply to a large sample of individuals containing few close relatives. It is fast because it, like all previous estimators, estimates Δ only and does not make iterative updates of allele frequencies by accounting for the inferred relatedness through the EM algorithm. EMIBD9 has both methods implemented for multiple computer platforms (Windows, Mac and Linux), and the Windows version has a GUI that facilitates data input and results visualisation. The GUI can also be used to simulate genotype data which are used to investigate factors affecting relatedness estimation accuracy, to optimise the experimental design of a relatedness study, and to compare the performance of different relatedness estimators.
{"title":"EMIBD9: Estimating 9 condensed IBD coefficients, inbreeding and relatedness from marker genotypes","authors":"Jinliang Wang","doi":"10.1038/s41437-024-00739-5","DOIUrl":"10.1038/s41437-024-00739-5","url":null,"abstract":"EMIBD9 is a computer programme implementing two likelihood methods for estimating the 9 condensed IBD coefficients, Δ = {Δ1, Δ2, …, Δ9}, between a pair of individuals from their genotype data. Inbreeding coefficients of and relatedness (or kinship coefficient) between individuals are then calculated from the estimated Δ. One method is designed to apply to a small sample or a sample containing a high proportion of close relatives where allele frequencies and their powers or products are poorly estimated by assuming a large sample of non-inbred and unrelated individuals. It adopts an expectation maximisation (EM) algorithm to estimate both Δ and allele frequencies jointly and iteratively. The other method is designed to apply to a large sample of individuals containing few close relatives. It is fast because it, like all previous estimators, estimates Δ only and does not make iterative updates of allele frequencies by accounting for the inferred relatedness through the EM algorithm. EMIBD9 has both methods implemented for multiple computer platforms (Windows, Mac and Linux), and the Windows version has a GUI that facilitates data input and results visualisation. The GUI can also be used to simulate genotype data which are used to investigate factors affecting relatedness estimation accuracy, to optimise the experimental design of a relatedness study, and to compare the performance of different relatedness estimators.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 3-4","pages":"155-161"},"PeriodicalIF":3.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41437-024-00739-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-24DOI: 10.1038/s41437-025-00757-x
Eduardo P. Cappa, Charles Chen, Jennifer G. Klutsch, Jaime Sebastian-Azcona, Blaise Ratcliffe, Xiaojing Wei, Letitia Da Ros, Yang Liu, Sudarshana Reddy Bhumireddy, Andy Benowicz, Shawn D. Mansfield, Nadir Erbilgin, Barb R. Thomas, Yousry A. El-Kassaby
{"title":"Correction: Revealing stable SNPs and genomic prediction insights across environments enhance breeding strategies of productivity, defense, and climate-adaptability traits in white spruce","authors":"Eduardo P. Cappa, Charles Chen, Jennifer G. Klutsch, Jaime Sebastian-Azcona, Blaise Ratcliffe, Xiaojing Wei, Letitia Da Ros, Yang Liu, Sudarshana Reddy Bhumireddy, Andy Benowicz, Shawn D. Mansfield, Nadir Erbilgin, Barb R. Thomas, Yousry A. El-Kassaby","doi":"10.1038/s41437-025-00757-x","DOIUrl":"10.1038/s41437-025-00757-x","url":null,"abstract":"","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 3-4","pages":"247-247"},"PeriodicalIF":3.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41437-025-00757-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-22DOI: 10.1038/s41437-025-00752-2
Alice M. Godden, Willian T. A. F. Silva, Berrit Kiehl, Cécile Jolly, Leighton Folkes, Ghazal Alavioon, Simone Immler
Environmental factors affect not only paternal condition but may translate into the following generations where sperm-mediated small RNAs (sRNAs) can contribute to the transmission of paternal effects. sRNAs play a key role in the male germ line in genome maintenance and repair, and particularly in response to environmental stress and the resulting increase in transposable element (TE) activity. Here, we investigated how the social environment (high competition, low competition) of male zebrafish Danio rerio affects sRNAs in sperm and how these are linked to gene expression and TE activity in their offspring. In a first experiment, we collected sperm samples after exposing males to each social environment for 2 weeks to test for differentially expressed sperm micro- (miRNA) and piwi-interacting RNAs (piRNA). In a separate experiment, we performed in vitro fertilisations after one 2-week period using a split-clutch design to control for maternal effects and collected embryos at 24 h to test for differentially expressed genes and TEs. We developed new computational prediction tools to link sperm sRNAs with differentially expressed TEs and genes in the embryos. Our results support the idea that the molecular stress response in the male germ line has significant down-stream effects on the molecular pathways, and we provide a direct link between sRNAs, TEs and gene expression.
{"title":"Environmentally induced variation in sperm sRNAs is linked to gene expression and transposable elements in zebrafish offspring","authors":"Alice M. Godden, Willian T. A. F. Silva, Berrit Kiehl, Cécile Jolly, Leighton Folkes, Ghazal Alavioon, Simone Immler","doi":"10.1038/s41437-025-00752-2","DOIUrl":"10.1038/s41437-025-00752-2","url":null,"abstract":"Environmental factors affect not only paternal condition but may translate into the following generations where sperm-mediated small RNAs (sRNAs) can contribute to the transmission of paternal effects. sRNAs play a key role in the male germ line in genome maintenance and repair, and particularly in response to environmental stress and the resulting increase in transposable element (TE) activity. Here, we investigated how the social environment (high competition, low competition) of male zebrafish Danio rerio affects sRNAs in sperm and how these are linked to gene expression and TE activity in their offspring. In a first experiment, we collected sperm samples after exposing males to each social environment for 2 weeks to test for differentially expressed sperm micro- (miRNA) and piwi-interacting RNAs (piRNA). In a separate experiment, we performed in vitro fertilisations after one 2-week period using a split-clutch design to control for maternal effects and collected embryos at 24 h to test for differentially expressed genes and TEs. We developed new computational prediction tools to link sperm sRNAs with differentially expressed TEs and genes in the embryos. Our results support the idea that the molecular stress response in the male germ line has significant down-stream effects on the molecular pathways, and we provide a direct link between sRNAs, TEs and gene expression.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 3-4","pages":"234-246"},"PeriodicalIF":3.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41437-025-00752-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-18DOI: 10.1038/s41437-025-00756-y
Fotis Pappas, Martin Johnsson, Göran Andersson, Paul V. Debes, Christos Palaiokostas
Differential DNA methylation due to epigenetic phenomena is crucial in regulating gene expression. Understanding the consequences of such differential expression on sperm quality parameters may provide insights into the underlying mechanisms of male reproductive success. Nonetheless, male fertility in fish remains understudied despite its critical importance to overall reproductive success in nature and captivity. This study investigated the DNA methylation landscape in spermatozoa of domesticated Arctic charr (Salvelinus alpinus) and its associations with sperm quality parameters. Computer assisted-semen analysis (CASA) was performed in 47 sperm samples of farmed Arctic charr, followed by enzymatic methylation sequencing (EM-seq). Our results showed that the DNA of Arctic charr sperm is highly methylated (mean value of ~86%), though variations were observed in genomic features involved in gene regulation. Methylation at variable CpG sites exhibited regional correlation decaying by physical distance, while methylation similarities among individuals were strongly coupled with genetic variation and mirrored pedigree structure. Comethylation network analyses for promoters, CpG islands and first introns revealed genomic modules significantly correlated with sperm quality traits (p < 0.05; Bonferroni adjusted), with distinct patterns suggesting a resource trade-off between sperm concentration and kinematics. Furthermore, annotation and gene-set enrichment analysis highlighted biological mechanisms related to spermatogenesis, cytoskeletal regulation, and mitochondrial function, all vital to sperm physiology. These findings suggest that DNA methylation is a critical and fundamental factor influencing male fertility in Arctic charr, providing insights into the underlying mechanisms of male reproductive success.
{"title":"Sperm DNA methylation landscape and its links to male fertility in a non-model teleost using EM-seq","authors":"Fotis Pappas, Martin Johnsson, Göran Andersson, Paul V. Debes, Christos Palaiokostas","doi":"10.1038/s41437-025-00756-y","DOIUrl":"10.1038/s41437-025-00756-y","url":null,"abstract":"Differential DNA methylation due to epigenetic phenomena is crucial in regulating gene expression. Understanding the consequences of such differential expression on sperm quality parameters may provide insights into the underlying mechanisms of male reproductive success. Nonetheless, male fertility in fish remains understudied despite its critical importance to overall reproductive success in nature and captivity. This study investigated the DNA methylation landscape in spermatozoa of domesticated Arctic charr (Salvelinus alpinus) and its associations with sperm quality parameters. Computer assisted-semen analysis (CASA) was performed in 47 sperm samples of farmed Arctic charr, followed by enzymatic methylation sequencing (EM-seq). Our results showed that the DNA of Arctic charr sperm is highly methylated (mean value of ~86%), though variations were observed in genomic features involved in gene regulation. Methylation at variable CpG sites exhibited regional correlation decaying by physical distance, while methylation similarities among individuals were strongly coupled with genetic variation and mirrored pedigree structure. Comethylation network analyses for promoters, CpG islands and first introns revealed genomic modules significantly correlated with sperm quality traits (p < 0.05; Bonferroni adjusted), with distinct patterns suggesting a resource trade-off between sperm concentration and kinematics. Furthermore, annotation and gene-set enrichment analysis highlighted biological mechanisms related to spermatogenesis, cytoskeletal regulation, and mitochondrial function, all vital to sperm physiology. These findings suggest that DNA methylation is a critical and fundamental factor influencing male fertility in Arctic charr, providing insights into the underlying mechanisms of male reproductive success.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 5","pages":"293-305"},"PeriodicalIF":3.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41437-025-00756-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-17DOI: 10.1038/s41437-025-00755-z
Esteban J. Jurcic, Joaquín Dutour, Pamela V. Villalba, Carmelo Centurión, Rodolfo J. C. Cantet, Sebastián Munilla, Eduardo P. Cappa
Traditionally, a pedigree-based individual-tree mixed model (ABLUP) has been used in forest genetic evaluations to identify individuals with the highest breeding values (BVs). ABLUP is a Markovian causal model, as any individual BV can be expressed as a linear regression on its parental BVs. The regression coefficients are based on the genealogical parent-offspring relationship and are equal to one-half. This study aimed to develop and apply two new causal models that replace these fixed coefficients with ones calculated using genomic information, specifically derived from the genomic-based relationship matrix. We compared the performance of these genomic-based causal models with ABLUP and non-causal GBLUP models. To do so, we evaluated a four-generation population of Eucalyptus grandis, consisting of 3082 genotyped trees with 14,033 single nucleotide polymorphism markers. Six traits were assessed in 1219 trees across the first three breeding cycles. The heritability and genetic means estimates were higher in the causal pedigree- and genomic-based models compared to GBLUP. Realized genetic gains were similar across all models, but the causal models more closely matched the predicted gains than GBLUP. In turn, GBLUP demonstrated better predictive performance, albeit with lower precision. The causal models developed in this study enable discerning intra-familial variations in the predictions of BVs at a lower computational burden and offer a potential alternative to the GBLUP model.
{"title":"Forest tree breeding using genomic Markov causal models: a new approach to genomic tree breeding improvement","authors":"Esteban J. Jurcic, Joaquín Dutour, Pamela V. Villalba, Carmelo Centurión, Rodolfo J. C. Cantet, Sebastián Munilla, Eduardo P. Cappa","doi":"10.1038/s41437-025-00755-z","DOIUrl":"10.1038/s41437-025-00755-z","url":null,"abstract":"Traditionally, a pedigree-based individual-tree mixed model (ABLUP) has been used in forest genetic evaluations to identify individuals with the highest breeding values (BVs). ABLUP is a Markovian causal model, as any individual BV can be expressed as a linear regression on its parental BVs. The regression coefficients are based on the genealogical parent-offspring relationship and are equal to one-half. This study aimed to develop and apply two new causal models that replace these fixed coefficients with ones calculated using genomic information, specifically derived from the genomic-based relationship matrix. We compared the performance of these genomic-based causal models with ABLUP and non-causal GBLUP models. To do so, we evaluated a four-generation population of Eucalyptus grandis, consisting of 3082 genotyped trees with 14,033 single nucleotide polymorphism markers. Six traits were assessed in 1219 trees across the first three breeding cycles. The heritability and genetic means estimates were higher in the causal pedigree- and genomic-based models compared to GBLUP. Realized genetic gains were similar across all models, but the causal models more closely matched the predicted gains than GBLUP. In turn, GBLUP demonstrated better predictive performance, albeit with lower precision. The causal models developed in this study enable discerning intra-familial variations in the predictions of BVs at a lower computational burden and offer a potential alternative to the GBLUP model.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 5","pages":"280-292"},"PeriodicalIF":3.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although depression significantly impacts fitness, some hypotheses suggest that it may offer a survival benefit. However, there has been limited systematic investigation into the selection pressures acting on genes associated with depression at the genomic level. Here, we conducted comparative genomic analyses and computational molecular evolutionary analyses on 320 depression-associated genes at two levels, i.e., across the primate phylogeny (long timescale selection) and in modern human populations (recent selection). We identified seven genes under positive selection in the human lineage, and 46 genes under positive selection in modern human populations. Most positively selected variants in modern human populations were at UTR regions and non-coding exons, indicating the importance of gene expression regulation in the evolution of depression-associated genes. Positively selected genes are not only related to immune responses, but also function in reproduction and dietary adaptation. Notably, the proportion of depression-associated genes under positive selection was significantly higher than the positively selected genes at the genome-wide average level in African, East Asian, and South Asian populations. We also identified two positively selected loci that happened to be associated with depression in the South Asian population. Our study revealed that depression-associated genes are subject to varying selection pressures across different populations. We suggest that, in precision medicine—particularly in gene therapy—it is crucial to consider the specific functions of genes within distinct populations.
{"title":"Detection of positive selection on depression-associated genes","authors":"Shiyu Yang, Chenqing Zheng, Canwei Xia, Jihui Kang, Langyu Gu","doi":"10.1038/s41437-025-00753-1","DOIUrl":"10.1038/s41437-025-00753-1","url":null,"abstract":"Although depression significantly impacts fitness, some hypotheses suggest that it may offer a survival benefit. However, there has been limited systematic investigation into the selection pressures acting on genes associated with depression at the genomic level. Here, we conducted comparative genomic analyses and computational molecular evolutionary analyses on 320 depression-associated genes at two levels, i.e., across the primate phylogeny (long timescale selection) and in modern human populations (recent selection). We identified seven genes under positive selection in the human lineage, and 46 genes under positive selection in modern human populations. Most positively selected variants in modern human populations were at UTR regions and non-coding exons, indicating the importance of gene expression regulation in the evolution of depression-associated genes. Positively selected genes are not only related to immune responses, but also function in reproduction and dietary adaptation. Notably, the proportion of depression-associated genes under positive selection was significantly higher than the positively selected genes at the genome-wide average level in African, East Asian, and South Asian populations. We also identified two positively selected loci that happened to be associated with depression in the South Asian population. Our study revealed that depression-associated genes are subject to varying selection pressures across different populations. We suggest that, in precision medicine—particularly in gene therapy—it is crucial to consider the specific functions of genes within distinct populations.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 5","pages":"263-272"},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41437-025-00753-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-13DOI: 10.1038/s41437-025-00754-0
Mark Milhaven, Aman Garg, Cyril J. Versoza, Susanne P. Pfeifer
The rate of spontaneous (de novo) germline mutation is a key parameter in evolutionary biology, impacting genetic diversity and contributing to the evolution of populations and species. Mutation rates themselves evolve over time but the mechanisms underlying the mutation rate variation observed across the Tree of Life remain largely to be elucidated. In recent years, whole genome sequencing has enabled the estimation of mutation rates for several organisms. However, due to a lack of community standards, many previous studies differ both empirically – most notably, in the depth of sequencing used to reliably identify de novo mutations – and computationally – utilizing different computational pipelines to detect germline mutations as well as different analysis strategies to mitigate technical artifacts – rendering comparisons between studies challenging. Using a pedigree of Western chimpanzees as an illustrative example, we here quantify the effects of commonly utilized quality metrics to reliably identify de novo mutations at different levels of sequencing coverage. We demonstrate that datasets with a mean depth of ≤ 30X are ill-suited for the detection of de novo mutations due to high false positive rates that can only be partially mitigated by computational filter criteria. In contrast, higher coverage datasets enable a comprehensive identification of de novo mutations at low false positive rates, with minimal benefits beyond a sequencing coverage of 60X, suggesting that future work should favor breadth (by sequencing additional individuals) over depth. Importantly, the simulation and analysis framework described here provides conceptual guidelines that will allow researchers to take study design and species-specific resources into account when determining computational filtering strategies for their organism of interest.
{"title":"Quantifying the effects of computational filter criteria on the accurate identification of de novo mutations at varying levels of sequencing coverage","authors":"Mark Milhaven, Aman Garg, Cyril J. Versoza, Susanne P. Pfeifer","doi":"10.1038/s41437-025-00754-0","DOIUrl":"10.1038/s41437-025-00754-0","url":null,"abstract":"The rate of spontaneous (de novo) germline mutation is a key parameter in evolutionary biology, impacting genetic diversity and contributing to the evolution of populations and species. Mutation rates themselves evolve over time but the mechanisms underlying the mutation rate variation observed across the Tree of Life remain largely to be elucidated. In recent years, whole genome sequencing has enabled the estimation of mutation rates for several organisms. However, due to a lack of community standards, many previous studies differ both empirically – most notably, in the depth of sequencing used to reliably identify de novo mutations – and computationally – utilizing different computational pipelines to detect germline mutations as well as different analysis strategies to mitigate technical artifacts – rendering comparisons between studies challenging. Using a pedigree of Western chimpanzees as an illustrative example, we here quantify the effects of commonly utilized quality metrics to reliably identify de novo mutations at different levels of sequencing coverage. We demonstrate that datasets with a mean depth of ≤ 30X are ill-suited for the detection of de novo mutations due to high false positive rates that can only be partially mitigated by computational filter criteria. In contrast, higher coverage datasets enable a comprehensive identification of de novo mutations at low false positive rates, with minimal benefits beyond a sequencing coverage of 60X, suggesting that future work should favor breadth (by sequencing additional individuals) over depth. Importantly, the simulation and analysis framework described here provides conceptual guidelines that will allow researchers to take study design and species-specific resources into account when determining computational filtering strategies for their organism of interest.","PeriodicalId":12991,"journal":{"name":"Heredity","volume":"134 5","pages":"273-279"},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41437-025-00754-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1038/s41437-025-00749-x
Barbora Bergelová, Václav Gvoždík, Martin Knytl
Chromosomal rearrangements are fundamental evolutionary drivers leading to genomic diversification. African clawed frogs (genus Xenopus, subgenera Silurana and Xenopus) represent an allopolyploid model system with conserved chromosome numbers in species with the same ploidy within each subgenus. Two significant interchromosomal rearrangements have been identified: a translocation between chromosomes 9 and 2, found in subgenus Silurana, and a fusion between chromosomes 9 and 10, probably widespread in subgenus Xenopus. Here, we study the allotetraploid Xenopus pygmaeus (subgenus Xenopus) based on in-depth karyotype analysis using chromosome measurements and fluorescent in situ hybridization (FISH). We designed FISH probes for genes associated with translocation and fusion to test for the presence of the two main types of rearrangements. We also examined the locations of 5S and 28S ribosomal tandem repeats, with the former often associated with telomeric regions and the latter with nucleolus organizer regions (NORs). The translocation-associated gene mapping did not detect the translocation in X. pygmaeus, supporting the hypothesis that the translocation is restricted to Silurana, but instead identified a pericentromeric inversion on chromosome 2S. The fusion-associated gene mapping confirmed the fusion of chromosomes 9 and 10, supporting this fusion as an ancestral state in subgenus Xenopus. As expected, the 5S repeats were found predominantly in telomere regions on almost all chromosomes. The nucleolar 28S repeats were localized on chromosome 6S, a position previously found only in the closely related species X. parafraseri, whereas other, phylogenetically more distant species have NORs located on different chromosomes. We therefore hypothesize that a jumping mechanism could explain the relatively frequent changes in the location of NORs during Xenopus evolution.
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