Project description:Centromeres are functionally conserved chromosomal loci essential for proper chromosome segregation during cell division, yet they show high sequence diversity across species. A near universal feature of centromeres is the presence of repetitive sequences, such as satellites and transposable elements (TEs). Because of their rapidly evolving karyotypes, gibbons represent a compelling model to investigate divergence of functional centromere sequences across short evolutionary timescales. Previously, we identified a novel composite retrotransposon, LAVA, that is exclusive to gibbons and expanded within the centromere regions of one gibbon genus, Hoolock. In this study, we use ChIP-seq, RNA-seq and fluorescence in situ hybridization to comprehensively investigate the repeat content of centromeres of the four extant gibbon genera (Hoolock, Hylobates, Nomascus and Siamang). We find that CENP-A nucleosomes and the DNA-protein interface with the inner kinetochore are enriched in retroelements in all gibbon genera, rather than satellite DNA. We find that LAVA in Hoolock is enriched in the centromeres of most chromosomes and shows centromere- and species-specific sequence and structural differences compared to other genera, potentially as a result of its co-option to a centromeric function. In contrast, we found that a centromeric retroelement-derived macrosatellite, SST1, corresponds with chromosome breakpoint reuse across gibbons and shows high sequence conservation across genera. Finally, using de novo assembly of centromere-specific sequences, we determine that transcripts originating from gibbon centromeres recapitulate species-specific TE diversity. Combined, our data reveals dynamic, species-specific shifts in repeat content that define gibbon centromeres and coincide with the extensive karyotypic diversity observed within this lineage.
Project description:Centromeres are functionally conserved chromosomal loci essential for proper chromosome segregation during cell division, yet they show high sequence diversity across species. A near universal feature of centromeres is the presence of repetitive sequences, such as satellites and transposable elements (TEs). Because of their rapidly evolving karyotypes, gibbons represent a compelling model to investigate divergence of functional centromere sequences across short evolutionary timescales. Previously, we identified a novel composite retrotransposon, LAVA, that is exclusive to gibbons and expanded within the centromere regions of one gibbon genus, Hoolock. In this study, we use ChIP-seq, RNA-seq and fluorescence in situ hybridization to comprehensively investigate the repeat content of centromeres of the four extant gibbon genera (Hoolock, Hylobates, Nomascus and Siamang). We find that CENP-A nucleosomes and the DNA-protein interface with the inner kinetochore are enriched in retroelements in all gibbon genera, rather than satellite DNA. We find that LAVA in Hoolock is enriched in the centromeres of most chromosomes and shows centromere- and species-specific sequence and structural differences compared to other genera, potentially as a result of its co-option to a centromeric function. In contrast, we found that a centromeric retroelement-derived macrosatellite, SST1, corresponds with chromosome breakpoint reuse across gibbons and shows high sequence conservation across genera. Finally, using de novo assembly of centromere-specific sequences, we determine that transcripts originating from gibbon centromeres recapitulate species-specific TE diversity. Combined, our data reveals dynamic, species-specific shifts in repeat content that define gibbon centromeres and coincide with the extensive karyotypic diversity observed within this lineage.
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:We report the application of DNA sequencing technology for high-throughput sequencing of mix bis-PCR products totally 38 based on bisulfate treated DNA from human, chimpanzee, gibbon, macaque and crab eating macaque profrontal cortex tissues. Mix bisulfate PCR products from 1 tissues, 23 individula humans, 2 individual chimpanzees, 1 individual gibbons, 7 individual rhesus macaques and 5 crab eating macaques were sequenced by using MiSeq
Project description:We report the application of DNA sequencing technology for high-throughput sequencing of mix candidate genes' PCR products totally 38 based on DNA from human, chimpanzee, gibbon, macaque and crab eating macaque profrontal cortex tissues. Mix candidate genes PCR products from 1 tissues, 22 individual humans, 2 individual chimpanzees, 1 individual gibbons,15 individual rhesus macaques and 5 crab eating macaques were sequenced by using MiSeq