scholarly journals Widespread misregulation of inter-species hybrid transcriptomes due to sex-specific and sex-chromosome regulatory evolution

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009409
Author(s):  
Santiago Sánchez-Ramírez ◽  
Jörg G. Weiss ◽  
Cristel G. Thomas ◽  
Asher D. Cutter
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Sex Chromosome ◽  
Sequence Divergence ◽  
Nematode Species ◽  
Stabilizing Selection ◽  
Species Hybrid ◽  
Hybrid Male ◽  
Specific Expression ◽  
Developmental Defects

When gene regulatory networks diverge between species, their dysfunctional expression in inter-species hybrid individuals can create genetic incompatibilities that generate the developmental defects responsible for intrinsic post-zygotic reproductive isolation. Both cis- and trans-acting regulatory divergence can be hastened by directional selection through adaptation, sexual selection, and inter-sexual conflict, in addition to cryptic evolution under stabilizing selection. Dysfunctional sex-biased gene expression, in particular, may provide an important source of sexually-dimorphic genetic incompatibilities. Here, we characterize and compare male and female/hermaphrodite transcriptome profiles for sibling nematode species Caenorhabditis briggsae and C. nigoni, along with allele-specific expression in their F1 hybrids, to deconvolve features of expression divergence and regulatory dysfunction. Despite evidence of widespread stabilizing selection on gene expression, misexpression of sex-biased genes pervades F1 hybrids of both sexes. This finding implicates greater fragility of male genetic networks to produce dysfunctional organismal phenotypes. Spermatogenesis genes are especially prone to high divergence in both expression and coding sequences, consistent with a “faster male” model for Haldane’s rule and elevated sterility of hybrid males. Moreover, underdominant expression pervades male-biased genes compared to female-biased and sex-neutral genes and an excess of cis-trans compensatory regulatory divergence for X-linked genes underscores a “large-X effect” for hybrid male expression dysfunction. Extensive regulatory divergence in sex determination pathway genes likely contributes to demasculinization of XX hybrids. The evolution of genetic incompatibilities due to regulatory versus coding sequence divergence, however, are expected to arise in an uncorrelated fashion. This study identifies important differences between the sexes in how regulatory networks diverge to contribute to sex-biases in how genetic incompatibilities manifest during the speciation process.

scholarly journals Widespread misregulation of inter-species hybrid transcriptomes due to sex-specific and sex-chromosome regulatory evolution

2020 ◽  
Author(s):  
Santiago Sánchez-Ramírez ◽  
Jörg G. Weiss ◽  
Cristel G. Thomas ◽  
Asher D. Cutter
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Regulatory Networks ◽  
Genetic Networks ◽  
Stabilizing Selection ◽  
Species Hybrid ◽  
Regulatory Evolution ◽  
Speciation Process ◽  
Gene Regulatory ◽  
Species Hybrids

AbstractWhen gene regulatory networks diverge between species, their dysfunctional expression in inter-species hybrid individuals can create genetic incompatibilities that generate the developmental defects responsible for intrinsic post-zygotic reproductive isolation. Both cis- and trans-acting regulatory divergence can be hastened by directional selection through adaptation, sexual selection, and inter-sexual conflict, in addition to inconspicuous evolution under stabilizing selection. Dysfunctional sex-biased gene expression, in particular, may provide an important source of sexually-dimorphic genetic incompatibilities. Here, we characterize and compare male and female/hermaphrodite transcriptome profiles for sibling nematode species Caenorhabditis briggsae and C. nigoni, along with allele-specific expression in their F1 hybrids, to deconvolve features of expression divergence and regulatory dysfunction. Despite evidence of widespread stabilizing selection on gene expression, misexpression of sex-biased genes pervades F1 hybrids of both sexes. This finding implicates greater fragility of male genetic networks to produce dysfunctional organismal phenotypes. Spermatogenesis genes are especially prone to high divergence in both expression and coding sequences, consistent with a “faster male” model for Haldane’s rule and elevated sterility of hybrid males. Moreover, underdominant expression pervades male-biased genes compared to female-biased and sex-neutral genes and an excess of cis-trans compensatory regulatory divergence for X-linked genes underscores a “large-X effect” for hybrid male expression dysfunction. Extensive regulatory divergence in sex determination pathway genes likely contributes to feminization of XX hybrids. The evolution of genetic incompatibilities due to regulatory versus coding sequence divergence, however, are expected arise in an uncorrelated fashion. This study identifies important differences between the sexes in how regulatory networks diverge to contribute to sex-biases in how genetic incompatibilities manifest during the speciation process.Author’s summaryAs species diverge, many mutations that affect traits do so by altering gene expression. Such gene regulatory changes also accumulate in the control of static traits, due to compensatory effects of mutation on multiple regulatory elements. Theory predicts many of these changes to cause inter-species hybrids to experience dysfunctional gene expression that leads to reduced fitness, disproportionately affecting genes biased toward expression in one sex and that localize to sex chromosomes. Our analyses of genome-wide gene expression from Caenorhabditis nematode roundworms support these predictions. We find widespread rewiring of gene regulation, despite the extensive morphological stasis and conserved expression profiles that are hallmarks of these animals. Misregulation of expression in inter-species hybrids of both sexes is most severe for genes linked to the X-chromosome, but male organismal phenotypes are most disrupted in hybrids. This fragility of male genetic networks and sex differences in regulatory evolution of local versus distant elements may underlie feminized and sterile phenotypes among hybrids. Our work clarifies how distinct components of regulatory networks evolve and contribute to sex differences in the manifestation of genetic incompatibilities in the speciation process.

scholarly journals Gene Expression Networks in the Drosophila Genetic Reference Panel

2019 ◽  
Author(s):  
Logan J. Everett ◽  
Wen Huang ◽  
Shanshan Zhou ◽  
Mary Anna Carbone ◽  
Richard F. Lyman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Dna Sequences ◽  
Quantitative Trait ◽  
Regulatory Networks ◽  
Target Genes ◽  
Reference Panel ◽  
Modern Biology ◽  
Specific Expression ◽  
Drosophila Genetic Reference Panel

SummaryA major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. Here, we performed deep RNA sequencing of 200 Drosophila Genetic Reference Panel inbred lines with complete genome sequences, and mapped expression quantitative trait loci for annotated genes, novel transcribed regions (most of which are long noncoding RNAs), transposable elements and microbial species. We identified host variants that affect expression of transposable elements, independent of their copy number, as well as microbiome composition. We constructed sex-specific expression quantitative trait locus regulatory networks. These networks are enriched for novel transcribed regions and target genes in heterochromatin and euchromatic regions of reduced recombination, and genes regulating transposable element expression. This study provides new insights regarding the role of natural genetic variation in regulating gene expression and generates testable hypotheses for future functional analyses.

scholarly journals Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Colin D Meiklejohn ◽  
Emily L Landeen ◽  
Kathleen E Gordon ◽  
Thomas Rzatkiewicz ◽  
Sarah B Kingan ◽  
...  
Keyword(s):  
Gene Flow ◽  
Sex Chromosomes ◽  
Population Genomics ◽  
Sex Chromosome ◽  
Hybrid Sterility ◽  
Sequence Divergence ◽  
Meiotic Drive ◽  
Hybrid Male ◽  
Local Sequence

During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of divergent cryptic sex-linked drive systems and, incidentally, genetic incompatibilities. To assess the role of drive during speciation, we combine high-resolution genetic mapping of X-linked hybrid male sterility with population genomics analyses of divergence and recent gene flow between the fruitfly species, Drosophila mauritiana and D. simulans. Our findings reveal a high density of genetic incompatibilities and a corresponding dearth of gene flow on the X chromosome. Surprisingly, we find that a known drive element recently migrated between species and, rather than contributing to interspecific divergence, caused a strong reduction in local sequence divergence, undermining the evolution of hybrid sterility. Gene flow can therefore mediate the effects of selfish genetic elements during speciation.

scholarly journals Intraspecific sequence and gene expression variation contribute little to venom diversity in sidewinder rattlesnakes ( Crotalus cerastes )

2019 ◽  
Vol 286 (1906) ◽  
pp. 20190810 ◽  
Author(s):  
Rhett M. Rautsaw ◽  
Erich P. Hofmann ◽  
Mark J. Margres ◽  
Matthew L. Holding ◽  
Jason L. Strickland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Complex Traits ◽  
Sequence Divergence ◽  
Protein Sequences ◽  
Venom Gland ◽  
Stabilizing Selection ◽  
Protein Coding ◽  
Standing Variation ◽  
Crotalus Cerastes

Traits can evolve rapidly through changes in gene expression or protein-coding sequences. However, these forms of genetic variation can be correlated and changes to one can influence the other. As a result, we might expect traits lacking differential expression to preferentially evolve through changes in protein sequences or morphological adaptation. Given the lack of differential expression across the distribution of sidewinder rattlesnakes ( Crotalus cerastes ), we tested this hypothesis by comparing the coding regions of genes expressed in the venom gland transcriptomes and fang morphology. We calculated Tajima's D and F ST across four populations comparing toxin and nontoxin loci. Overall, we found little evidence of directional selection or differentiation between populations, suggesting that changes to protein sequences do not underlie the evolution of sidewinder venom or that toxins are under extremely variant selection pressures. Although low-expression toxins do not have higher sequence divergence between populations, they do have more standing variation on which selection can act. Additionally, we found significant differences in fang length among populations. The lack of differential expression and sequence divergence suggests sidewinders—given their generalist diet, moderate gene flow and environmental variation—are under stabilizing selection which functions to maintain a generalist phenotype. Overall, we demonstrate the importance of examining the relationship between gene expression and protein-coding changes to understand the evolution of complex traits.

scholarly journals Evaluating the Effect of 3′-UTR Variants in DICER1 and DROSHA on Their Tissue-Specific Expression by miRNA Target Prediction

2021 ◽  
Vol 43 (2) ◽  
pp. 605-617
Author(s):  
Dmitrii S. Bug ◽  
Artem V. Tishkov ◽  
Ivan S. Moiseev ◽  
Natalia V. Petukhova
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Mirna Target ◽  
Target Prediction ◽  
Specific Gene ◽  
Phenotypic Effect ◽  
Specific Expression ◽  
Form Complex ◽  
Tissue Specific

Untranslated gene regions (UTRs) play an important role in controlling gene expression. 3′-UTRs are primarily targeted by microRNA (miRNA) molecules that form complex gene regulatory networks. Cancer genomes are replete with non-coding mutations, many of which are connected to changes in tumor gene expression that accompany the development of cancer and are associated with resistance to therapy. Therefore, variants that occurred in 3′-UTR under cancer progression should be analysed to predict their phenotypic effect on gene expression, e.g., by evaluating their impact on miRNA target sites. Here, we analyze 3′-UTR variants in DICER1 and DROSHA genes in the context of myelodysplastic syndrome (MDS) development. The key features of this analysis include an assessment of both “canonical” and “non-canonical” types of mRNA-miRNA binding and tissue-specific profiling of miRNA interactions with wild-type and mutated genes. As a result, we obtained a list of DICER1 and DROSHA variants likely altering the miRNA sites and, therefore, potentially leading to the observed tissue-specific gene downregulation. All identified variants have low population frequency consistent with their potential association with pathology progression.

scholarly journals Sex-biased gene expression and recent sex chromosome turnover

2021 ◽  
Vol 376 (1833) ◽  
pp. 20200107 ◽  
Author(s):  
Nicolás Lichilín ◽  
Athimed El Taher ◽  
Astrid Böhne
Keyword(s):  
Gene Expression ◽  
Sexual Conflict ◽  
Sex Chromosome ◽  
Sequence Divergence ◽  
Sex Bias ◽  
Sequence Evolution ◽  
Phylogenetic Constraint ◽  
Evolutionary Changes ◽  
Chromosome Sequence ◽  
Evolutionary Pace

Cichlids are well known for their propensity to radiate generating arrays of morphologically and ecologically diverse species in short evolutionary time. Following this rapid evolutionary pace, cichlids show high rates of sex chromosome turnover. We here studied the evolution of sex-biased gene (SBG) expression in 14 recently diverged taxa of the Lake Tanganyika Tropheini cichlids, which show different XY sex chromosomes. Across species, sex chromosome sequence divergence predates divergence in expression between the sexes. Only one sex chromosome, the oldest, showed signs of demasculinization in gene expression and potentially contribution to the resolution of sexual conflict. SBGs in general showed high rates of turnovers and evolved mostly under drift. Sexual selection did not shape the rapid evolutionary changes of SBGs. Male-biased genes evolved faster than female-biased genes, which seem to be under more phylogenetic constraint. We found a relationship between the degree of sex bias and sequence evolution driven by sequence differences among the sexes. Consistent with other species, strong sex bias towards sex-limited expression contributes to resolving sexual conflict in cichlids. This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.

scholarly journals Rampant Misexpression in a Mimulus (Monkeyflower) Introgression Line Caused by Hybrid Sterility, Not Regulatory Divergence

2020 ◽  
Vol 37 (7) ◽  
pp. 2084-2098 ◽  
Author(s):  
Rachel E Kerwin ◽  
Andrea L Sweigart
Keyword(s):  
Male Sterility ◽  
Gene Expression Regulation ◽  
Hybrid Sterility ◽  
Introgression Line ◽  
Transcript Abundance ◽  
Stabilizing Selection ◽  
Hybrid Male ◽  
Specific Expression ◽  
Hybrid Male Sterility ◽  
Genome Wide

Abstract Divergence in gene expression regulation is common between closely related species and may give rise to incompatibilities in their hybrid progeny. In this study, we investigated the relationship between regulatory evolution within species and reproductive isolation between species. We focused on a well-studied case of hybrid sterility between two closely related yellow monkeyflower species, Mimulus guttatus and Mimulus nasutus, that is caused by two epistatic loci, hybrid male sterility 1 (hms1) and hybrid male sterility 2 (hms2). We compared genome-wide transcript abundance across male and female reproductive tissues (i.e., stamens and carpels) from four genotypes: M. guttatus, M. nasutus, and sterile and fertile progeny from an advanced M. nasutus–M. guttatus introgression line carrying the hms1–hms2 incompatibility. We observed substantial variation in transcript abundance between M. guttatus and M. nasutus, including distinct but overlapping patterns of tissue-biased expression, providing evidence for regulatory divergence between these species. We also found rampant genome-wide misexpression, but only in the affected tissues (i.e., stamens) of sterile introgression hybrids carrying incompatible alleles at hms1 and hms2. Examining patterns of allele-specific expression in sterile and fertile introgression hybrids, we found evidence for interspecific divergence in cis- and trans-regulation, including compensatory cis–trans mutations likely to be driven by stabilizing selection. Nevertheless, species divergence in gene regulatory networks cannot explain the vast majority of the gene misexpression we observe in Mimulus introgression hybrids, which instead likely manifests as a downstream consequence of sterility itself.

scholarly journals HAHmiR.DB: A Server Platform For High Altitude Human miRNA-Gene Coregulatory Networks And Associated Regulatory-Circuits

2020 ◽  
Author(s):  
Apoorv Gupta ◽  
Ragumani Sugadev ◽  
Yogendra Kumar Sharma ◽  
Bhuvnesh Kumar ◽  
Pankaj Khurana
Keyword(s):  
Gene Expression ◽  
High Altitude ◽  
Regulatory Networks ◽  
Gene Expression Regulation ◽  
Mirna Gene ◽  
Adaptive Responses ◽  
Specific Expression ◽  
Regulatory Circuits ◽  
Rapid Ascent ◽  
Tf Gene

AbstractRapid ascent to High Altitude (HA) can cause severe damage to body organs and may lead to many fatal disorders. During induction to HA, human body undergoes various physiological, biochemical, hematological and molecular changes to adapt to the extreme environmental conditions. Many literature references hint that gene-expression-regulation and regulatory molecules like microRNAs (miRNAs) and Transcription Factors (TFs) control adaptive responses during HA-stress. These biomolecules are known to interact in a complex combinatorial manner to fine-tune the gene expression and help in controlling the molecular responses during this stress and ultimately help in acclimatization. HAHmiR.DB (High-Altitude Human miRNA Database) is a unique, comprehensive, curated collection of miRNAs that have been experimentally validated to be associated with HA-stress; their level of expression in different altitudes, fold change, experiment duration, biomarker association, disease and drug association, tissue-specific expression level, Gene Ontology (GO) and Kyoto Encyclopaedia of Gene and Genomes (KEGG) pathway associations. As a server platform it also uniquely constructs and analyses interactive miRNA-TF-Gene coregulatory networks and extracts regulatory-circuits/Feed Forward Loops (FFLs) using in-house scripts. These regulatory circuits help to offer mechanistic insights in complex regulatory mechanisms during HA stress. The server can also build these regulatory networks between two and more miRNAs of the database and also identify the regulatory-circuits from this network. Hence HAHmiR.DB is the first-of its-kind database in HA research which a reliable platform to explore, compare, analyse and retrieve miRNAs associated with HA stress, their coregulatory networks and FFL regulatory circuits. HAHmiR.DB is freely accessible at http://www.hahmirdb.in

scholarly journals HAHmiR.DB: a server platform for high-altitude human miRNA–gene coregulatory networks and associated regulatory circuits

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Pankaj Khurana ◽  
Apoorv Gupta ◽  
Ragumani Sugadev ◽  
Yogendra Kumar Sharma ◽  
Bhuvnesh Kumar
Keyword(s):  
Gene Expression ◽  
High Altitude ◽  
Regulatory Networks ◽  
Gene Expression Regulation ◽  
Mirna Gene ◽  
The Body ◽  
Adaptive Responses ◽  
Specific Expression ◽  
Regulatory Circuits ◽  
Tf Gene

Abstract Around 140 million people live in high-altitude (HA) conditions! and even a larger number visit such places for tourism, adventure-seeking or sports training. Rapid ascent to HA can cause severe damage to the body organs and may lead to many fatal disorders. During induction to HA, human body undergoes various physiological, biochemical, hematological and molecular changes to adapt to the extreme environmental conditions. Several literature references hint that gene-expression-regulation and regulatory molecules like miRNAs and transcription factors (TFs) control adaptive responses during HA stress. These biomolecules are known to interact in a complex combinatorial manner to fine-tune the gene expression and help in controlling the molecular responses during this stress and ultimately help in acclimatization. High-Altitude Human miRNA Database (HAHmiR.DB) is a unique, comprehensive and curated collection of miRNAs that have been experimentally validated to be associated with HA stress, their level of expression in different altitudes, fold change, experiment duration, biomarker association, disease and drug association, tissue-specific expression level, Gene Ontology (GO) and Kyoto Encyclopaedia of Gene and Genomes (KEGG) pathway associations. As a server platform, it also uniquely constructs and analyses interactive miRNA–TF–gene coregulatory networks and extracts regulatory circuits/feed-forward loops (FFLs). These regulatory circuits help to offer mechanistic insights into complex regulatory mechanisms during HA stress. The server can also build these regulatory networks between two and more miRNAs of the database and also identify the regulatory circuits from this network. Hence, HAHmiR.DB is the first-of-its-kind database in HA research, which is a reliable platform to explore, compare, analyse and retrieve miRNAs associated with HA stress, their coregulatory networks and FFL regulatory-circuits. HAHmiR.DB is freely accessible at http://www.hahmirdb.in

scholarly journals Gene Expression Networks Across Multiple Tissues Are Associated with Rates of Molecular Evolution in Wild House Mice

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 225 ◽  
Author(s):  
Katya Mack ◽  
Megan Phifer-Rixey ◽  
Bettina Harr ◽  
Michael Nachman
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Gene Evolution ◽  
Purifying Selection ◽  
Evolutionary Constraint ◽  
Mus Musculus Domesticus ◽  
Specific Expression ◽  
Regulatory Variation ◽  
Allele Specific ◽  
Wild House Mice

Interactions between genes can influence how selection acts on sequence variation. In gene regulatory networks, genes that affect the expression of many other genes may be under stronger evolutionary constraint than genes whose expression affects fewer partners. While this has been studied for individual tissue types, we know less about the effects of regulatory networks on gene evolution across different tissue types. We use RNA-sequencing and genomic data collected from Mus musculus domesticus to construct and compare gene co-expression networks for 10 tissue types. We identify tissue-specific expression and local regulatory variation, and we associate these components of gene expression variation with sequence polymorphism and divergence. We found that genes with higher connectivity across tissues and genes associated with a greater number of cross-tissue modules showed significantly lower genetic diversity and lower rates of protein evolution. Consistent with this pattern, “hub” genes across multiple tissues also showed evidence of greater evolutionary constraint. Using allele-specific expression, we found that genes with cis-regulatory variation had lower average connectivity and higher levels of tissue specificity. Taken together, these results are consistent with strong purifying selection acting on genes with high connectivity within and across tissues.

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