Project description:Co-option of transposable elements (TEs) to become part of existing or new enhancers is an important mechanism for evolution of gene regulation. However, contributions of lineage-specific TE insertions to recent regulatory adaptations remain poorly understood. Gibbons present a suitable model to study these contributions as they have evolved a lineage-specific TE called LAVA (LINE-AluSz-VNTR-AluLIKE), which is still active in the gibbon genome. The LAVA retrotransposon is thought to have played a role in the emergence of the highly rearranged structure of the gibbon genome by disrupting transcription of cell cycle genes. In this study, we investigated whether LAVA may have also contributed to the evolution of gene regulation by adopting enhancer function. We characterized fixed and polymorphic LAVA insertions across multiple gibbons and found 96 LAVA elements overlapping enhancer chromatin states. Moreover, LAVA was enriched in multiple transcription factor binding motifs, was bound by an important transcription factor (PU.1), and was associated with higher levels of gene expression in cis. We found gibbon-specific signatures of purifying/positive selection at 27 LAVA insertions. Two of these insertions were fixed in the gibbon lineage and overlapped with enhancer chromatin states, representing putative co-opted LAVA enhancers. These putative enhancers were located within genes encoding SETD2 and RAD9A, two proteins that facilitate accurate repair of DNA double-strand breaks and prevent chromosomal rearrangement mutations. Co-option of LAVA in these genes may have influenced regulation of processes that preserve genome integrity. Our findings highlight the importance of considering lineage-specific TEs in studying evolution of gene regulatory elements.
Project description:Co-option of transposable elements (TEs) to become part of existing or new enhancers is an important mechanism for evolution of gene regulation. However, contributions of lineage-specific TE insertions to recent regulatory adaptations remain poorly understood. Gibbons present a suitable model to study these contributions as they have evolved a lineage-specific TE called LAVA (LINE-AluSz-VNTR-AluLIKE), which is still active in the gibbon genome. The LAVA retrotransposon is thought to have played a role in the emergence of the highly rearranged structure of the gibbon genome by disrupting transcription of cell cycle genes. In this study, we investigated whether LAVA may have also contributed to the evolution of gene regulation by adopting enhancer function. We characterized fixed and polymorphic LAVA insertions across multiple gibbons and found 96 LAVA elements overlapping enhancer chromatin states. Moreover, LAVA was enriched in multiple transcription factor binding motifs, was bound by an important transcription factor (PU.1), and was associated with higher levels of gene expression in cis. We found gibbon-specific signatures of purifying/positive selection at 27 LAVA insertions. Two of these insertions were fixed in the gibbon lineage and overlapped with enhancer chromatin states, representing putative co-opted LAVA enhancers. These putative enhancers were located within genes encoding SETD2 and RAD9A, two proteins that facilitate accurate repair of DNA double-strand breaks and prevent chromosomal rearrangement mutations. Co-option of LAVA in these genes may have influenced regulation of processes that preserve genome integrity. Our findings highlight the importance of considering lineage-specific TEs in studying evolution of gene regulatory elements.
Project description:Co-option of transposable elements (TEs) to become part of existing or new enhancers is an important mechanism for evolution of gene regulation. However, contributions of lineage-specific TE insertions to recent regulatory adaptations remain poorly understood. Gibbons present a suitable model to study these contributions as they have evolved a lineage-specific TE called LAVA (LINE-AluSz-VNTR-AluLIKE), which is still active in the gibbon genome. The LAVA retrotransposon is thought to have played a role in the emergence of the highly rearranged structure of the gibbon genome by disrupting transcription of cell cycle genes. In this study, we investigated whether LAVA may have also contributed to the evolution of gene regulation by adopting enhancer function. We characterized fixed and polymorphic LAVA insertions across multiple gibbons and found 96 LAVA elements overlapping enhancer chromatin states. Moreover, LAVA was enriched in multiple transcription factor binding motifs, was bound by an important transcription factor (PU.1), and was associated with higher levels of gene expression in cis. We found gibbon-specific signatures of purifying/positive selection at 27 LAVA insertions. Two of these insertions were fixed in the gibbon lineage and overlapped with enhancer chromatin states, representing putative co-opted LAVA enhancers. These putative enhancers were located within genes encoding SETD2 and RAD9A, two proteins that facilitate accurate repair of DNA double-strand breaks and prevent chromosomal rearrangement mutations. Co-option of LAVA in these genes may have influenced regulation of processes that preserve genome integrity. Our findings highlight the importance of considering lineage-specific TEs in studying evolution of gene regulatory elements.
Project description:Co-option of transposable elements (TEs) to become part of existing or new enhancers is an important mechanism for evolution of gene regulation. However, contributions of lineage-specific TE insertions to recent regulatory adaptations remain poorly understood. Gibbons present a suitable model to study these contributions as they have evolved a lineage-specific TE called LAVA (LINE-AluSz-VNTR-AluLIKE), which is still active in the gibbon genome. The LAVA retrotransposon is thought to have played a role in the emergence of the highly rearranged structure of the gibbon genome by disrupting transcription of cell cycle genes. In this study, we investigated whether LAVA may have also contributed to the evolution of gene regulation by adopting enhancer function. We characterized fixed and polymorphic LAVA insertions across multiple gibbons and found 96 LAVA elements overlapping enhancer chromatin states. Moreover, LAVA was enriched in multiple transcription factor binding motifs, was bound by an important transcription factor (PU.1), and was associated with higher levels of gene expression in cis. We found gibbon-specific signatures of purifying/positive selection at 27 LAVA insertions. Two of these insertions were fixed in the gibbon lineage and overlapped with enhancer chromatin states, representing putative co-opted LAVA enhancers. These putative enhancers were located within genes encoding SETD2 and RAD9A, two proteins that facilitate accurate repair of DNA double-strand breaks and prevent chromosomal rearrangement mutations. Co-option of LAVA in these genes may have influenced regulation of processes that preserve genome integrity. Our findings highlight the importance of considering lineage-specific TEs in studying evolution of gene regulatory elements.
Project description:In this pioneering study, we present the first comprehensive catalog of 683 small non-coding miRNAs for Astyanax mexicanus. Focusing on an early developmental stage, miRNAs were extracted and sequenced from 24hpf embryos of surface fish and three distinct cavefish morphs (Pachón, Tinaja, and Molino). We utilized in silico analyses to predict putative 3’UTR targets of these miRNAs, revealing a unique and extensive miRNA landscape in cavefish. Small RNA sequencing identified over 100 differentially expressed miRNAs in each cave morph compared to surface fish at 24hpf, suggesting early activation of miRNA-mediated silencing pathways. Notably, a subset of miRNAs was common across all three cave morphs, constituting cave-specific miRNAs potentially instrumental in cave adaptation. To unravel the functional implications of these cave-specific miRNAs, we analyzed their predicted target genes. Gene Ontology (GO) term analysis unveiled pathways which align with known adaptations in cavefish, primarily affecting development and metabolism. Further, cross-validating with a sample mRNAseq data from Pachón and surface fish also strongly suggested impact of these miRNAs on cave adaptation associated pathways. This study establishes a foundation for exploring miRNA-mediated gene regulation in cavefish, shedding light on their potential role in regulating early developmental and metabolic adaptations crucial for troglomorphic features. The comprehensive miRNA catalog provided will also guide future investigations into the intricate world of miRNA-mediated evolution in cave-adapted species.
Project description:Organisms adapt to and survive in environments with varying nutrient availability. Cis-regulatory changes play important roles in adaptation and phenotypic evolution. To what extent cis-regulatory elements contribute to metabolic adaptation is less understood. Here we have utilized a unique vertebrate model, Astyanax mexicanus, that survives in nutrient rich surface and nutrient deprived cave water to uncover gene regulatory networks in metabolic adaptation. We performed genome-wide analysis of accessible chromatin and histone modifications in the liver tissue of one surface and two independently derived cave populations, providing the first genome-wide epigenetic landscape in this organism. We find that many cis-regulatory elements differ between surface and the cavefish, while the two independently derived cave populations have evolved remarkably similar regulatory signatures. Changes in gene regulatory networks between the surface and cave morphotypes point to global changes in key metabolic pathways.
Project description:Organisms adapt to and survive in environments with varying nutrient availability. Cis-regulatory changes play important roles in adaptation and phenotypic evolution. To what extent cis-regulatory elements contribute to metabolic adaptation is less understood. Here we have utilized a unique vertebrate model, Astyanax mexicanus, that survives in nutrient rich surface and nutrient deprived cave water to uncover gene regulatory networks in metabolic adaptation. We performed genome-wide analysis of accessible chromatin and histone modifications in the liver tissue of one surface and two independently derived cave populations, providing the first genome-wide epigenetic landscape in this organism. We find that many cis-regulatory elements differ between surface and the cavefish, while the two independently derived cave populations have evolved remarkably similar regulatory signatures. Changes in gene regulatory networks between the surface and cave morphotypes point to global changes in key metabolic pathways.
Project description:we report a transcriptome-wide comparative investigation between surface and cave species in Sinocyclocheilus. De novo transcriptome assemblies were performed on surface and cave species; then the Sinocyclocheilus contigs were annotated with Gene Ontology. RNA-Seq assays revealed reduced transcription of a series of visual phototransduction and retinal disease related genes in cave-dwelling species compared with surface species. Degeneration of the retina in Sinocyclocheilus cavefish might occur in a lens-independent way by the down-regulation of several transcriptional factors, which have direct roles in retina development and maintenance, such as crx, rorb and Wnt pathway members. Examination of 2 different eye samples in 2 Sinocyclocheilus species.