Project description:The relationship between evolutionary genome remodeling and the three-dimensional structure of the genome remain largely unexplored. Here we use the heavily rearranged gibbon genome to examine how evolutionary chromosomal rearrangements impact genome-wide chromatin interactions, topologically associating domains (TADs), and their epigenetic landscape. We use high-resolution maps of gibbon-human breaks of synteny (BOS), apply Hi-C in gibbon, measure an array of epigenetic features, and perform cross-species comparisons. We find that gibbon rearrangements occur at TAD boundaries, independent of the parameters used to identify TADs. This overlap is supported by a remarkable genetic and epigenetic similarity between BOS and TAD boundaries, namely presence of CpG islands and SINE elements, and enrichment in CTCF and H3K4me3 binding. Cross-species comparisons reveal that regions orthologous to BOS also correspond with boundaries of large (400-600kb) TADs in human and other mammalian species. The co-localization of rearrangement breakpoints and TAD boundaries may be due to higher chromatin fragility at these locations and/or increased selective pressure against rearrangements that disrupt TAD integrity. We also examine the small portion of BOS that did not overlap with TAD boundaries and gave rise to novel TADs in the gibbon genome. We postulate that these new TADs generally lack deleterious consequences. Lastly, we show that limited epigenetic homogenization occurs across breakpoints, irrespective of their time of occurrence in the gibbon lineage. Overall, our findings demonstrate remarkable conservation of chromatin interactions and epigenetic landscape in gibbons, in spite of extensive genomic shuffling.
Project description:The relationship between evolutionary genome remodeling and the three-dimensional structure of the genome remain largely unexplored. Here we use the heavily rearranged gibbon genome to examine how evolutionary chromosomal rearrangements impact genome-wide chromatin interactions, topologically associating domains (TADs), and their epigenetic landscape. We use high-resolution maps of gibbon-human breaks of synteny (BOS), apply Hi-C in gibbon, measure an array of epigenetic features, and perform cross-species comparisons. We find that gibbon rearrangements occur at TAD boundaries, independent of the parameters used to identify TADs. This overlap is supported by a remarkable genetic and epigenetic similarity between BOS and TAD boundaries, namely presence of CpG islands and SINE elements, and enrichment in CTCF and H3K4me3 binding. Cross-species comparisons reveal that regions orthologous to BOS also correspond with boundaries of large (400-600kb) TADs in human and other mammalian species. The co-localization of rearrangement breakpoints and TAD boundaries may be due to higher chromatin fragility at these locations and/or increased selective pressure against rearrangements that disrupt TAD integrity. We also examine the small portion of BOS that did not overlap with TAD boundaries and gave rise to novel TADs in the gibbon genome. We postulate that these new TADs generally lack deleterious consequences. Lastly, we show that limited epigenetic homogenization occurs across breakpoints, irrespective of their time of occurrence in the gibbon lineage. Overall, our findings demonstrate remarkable conservation of chromatin interactions and epigenetic landscape in gibbons, in spite of extensive genomic shuffling.
Project description:The relationship between evolutionary genome remodeling and the three-dimensional structure of the genome remain largely unexplored. Here we use the heavily rearranged gibbon genome to examine how evolutionary chromosomal rearrangements impact genome-wide chromatin interactions, topologically associating domains (TADs), and their epigenetic landscape. We use high-resolution maps of gibbon-human breaks of synteny (BOS), apply Hi-C in gibbon, measure an array of epigenetic features, and perform cross-species comparisons. We find that gibbon rearrangements occur at TAD boundaries, independent of the parameters used to identify TADs. This overlap is supported by a remarkable genetic and epigenetic similarity between BOS and TAD boundaries, namely presence of CpG islands and SINE elements, and enrichment in CTCF and H3K4me3 binding. Cross-species comparisons reveal that regions orthologous to BOS also correspond with boundaries of large (400-600kb) TADs in human and other mammalian species. The co-localization of rearrangement breakpoints and TAD boundaries may be due to higher chromatin fragility at these locations and/or increased selective pressure against rearrangements that disrupt TAD integrity. We also examine the small portion of BOS that did not overlap with TAD boundaries and gave rise to novel TADs in the gibbon genome. We postulate that these new TADs generally lack deleterious consequences. Lastly, we show that limited epigenetic homogenization occurs across breakpoints, irrespective of their time of occurrence in the gibbon lineage. Overall, our findings demonstrate remarkable conservation of chromatin interactions and epigenetic landscape in gibbons, in spite of extensive genomic shuffling.
Project description:Chromosome rearrangements in small apes are up to 20 times more frequent than in most mammals. Because of their complexity, the full extent of chromosome evolution in these hominoids is not yet fully documented. However, previous work with array painting, BAC-FISH and selective sequencing in two of the four karyomorphs, has shown that high resolution methods can precisely define chromosome breakpoints and map the complex flow of evolutionary chromosome rearrangements. Here we use these tools to precisely define the rearrangements that have occurred in the remaining two karyomorphs, genera Symphalangus (2n=50), and Hoolock (2n=38). This research provides the most comprehensive insight into the evolutionary origins of chromosome rearrangements involved in transforming small apes genome. Bioinformatics analyses of the human-gibbon synteny breakpoints revealed association with transposable elements and segmental duplications providing some insight into the mechanisms that might have promoted rearrangements in small apes. In the near future, the comparison of gibbon genome sequences will provide novel insights to test hypotheses concerning the mechanisms of chromosome evolution. The precise definition of synteny block boundaries and orientation, chromosomal fusions, and centromere repositioning event presented here will facilitate genome sequence assembly for these close relatives of humans.
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.
Project description:Whole genome sequencing (WGS) of tongue cancer samples and cell line was performed to identify the fusion gene translocation breakpoint. WGS raw data was aligned to human reference genome (GRCh38.p12) using BWA-MEM (v0.7.17). The BAM files generated were further analysed using SvABA (v1.1.3) tool to identify translocation breakpoints. The translocation breakpoints were annotated using custom scripts, using the reference GENCODE GTF (v30). The fusion breakpoints identified in the SvABA analysis were additionally confirmed using MANTA tool (v1.6.0).
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: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.
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