Project description:Gene order, or microsynteny, is generally thought not to be conserved across metazoan phyla. Only a handful of exceptions, typically of tandemly duplicated genes such as Hox genes, have been discovered. Here, we performed a systematic survey for microsynteny conservation in 17 genomes and identified nearly 600 pairs of unrelated genes that have remained together across over 600 million years of evolution. Using multiple genome-wide resources, including several genomic features, epigenetic marks, sequence conservation and microarray expression data, we provide extensive evidence that many of these ancient microsyntenic arrangements have been conserved in order to preserve either (i) the coordinated transcription of neighboring genes, or (ii) Genomic Regulatory Blocks (GRBs), in which transcriptional enhancers controlling key developmental genes are contained within nearby “bystander” genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos to further investigate putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results show that ancient genomic associations are far more common in modern metazoans than previously thought – likely involving over 12% of the ancestral bilaterian genome – and that cis-regulatory constraints have played a major role in conserving the architecture of metazoan genomes. ChIP-seq H3K27me3 of 24hpf zebrafish embryos
Project description:The Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in ancient samples. Here, we used a massively parallel reporter assay in embryonic stem cells, neural progenitor cells and bone osteoblasts to investigate the regulatory effects of the 14,042 single-nucleotide modern human-specific variants. Overall, 1,791 (13%) of sequences containing these variants showed active regulatory activity, and 407 (23%) of these drove differential expression between human groups. Differentially active sequences were associated with divergent transcription factor binding motifs, and with genes enriched for vocal tract and brain anatomy and function. This work provides insight into the regulatory function of variants that emerged along the modern human lineage and the recent evolution of human gene expression.
Project description:Gene order, or microsynteny, is generally thought not to be conserved across metazoan phyla. Only a handful of exceptions, typically of tandemly duplicated genes such as Hox genes, have been discovered. Here, we performed a systematic survey for microsynteny conservation in 17 genomes and identified nearly 600 pairs of unrelated genes that have remained together across over 600 million years of evolution. Using multiple genome-wide resources, including several genomic features, epigenetic marks, sequence conservation and microarray expression data, we provide extensive evidence that many of these ancient microsyntenic arrangements have been conserved in order to preserve either (i) the coordinated transcription of neighboring genes, or (ii) Genomic Regulatory Blocks (GRBs), in which transcriptional enhancers controlling key developmental genes are contained within nearby “bystander” genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos to further investigate putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results show that ancient genomic associations are far more common in modern metazoans than previously thought – likely involving over 12% of the ancestral bilaterian genome – and that cis-regulatory constraints have played a major role in conserving the architecture of metazoan genomes.
Project description:Ancient Isthmian genomes address anthropological questions on pre-contact burials.
The comparison with modern Panamanians highlights genomic structure on the Isthmus.
A genomic component drives the Isthmian groups on a distinctive variability axis.
A previously unknown Pleistocene ancestry identified in the Isthmo-Colombian area.