Project description:Genome wide DNA methylation profiling of brain and liver from human and chimpanzee. The Illumina HumanMethylation27 DNA Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs for each sample. Samples included liver and NeuN-positive/NeuN-negative/unsorted brain in three individuals from each of two species (human and chimpanzee).
Project description:Genome wide DNA methylation profiling of brain and liver from human and chimpanzee. The Illumina HumanMethylation27 DNA Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs for each sample. Samples included liver and NeuN-positive/NeuN-negative/unsorted brain in three individuals from each of two species (human and chimpanzee). Bisulphite converted DNA from the 24 samples were hybridised to the Illumina HumanMethylation27 Beadchip (HumanMethylation27_270596_v.1.2)
Project description:The origin of humans was accompanied by the emergence of new behavioral and cognitive functions, including language and specialized forms of abstract representation. However, the molecular foundations of these human capabilities are poorly understood. Because of the extensive similarity between human and chimpanzee DNA sequences, it has been suggested that many of the key phenotypic differences between species result primarily from alterations in the regulation of genes rather than in their sequences. To characterize gene expression patterns accross the brain and investigate the genetic basis of human specializations in brain organization and cognition, we used microarrays to quantify the transcript levels of thousands of genes in tissue samples from different brain regions of several human and chimpanzee individuals. Our results indicated that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans, and suggests that the human brain is characterized by elevated levels of neuronal activity. Keywords: Species comparative study
Project description:The origin of humans was accompanied by the emergence of new behavioral and cognitive functions, including language and specialized forms of abstract representation. However, the molecular foundations of these human capabilities are poorly understood. Because of the extensive similarity between human and chimpanzee DNA sequences, it has been suggested that many of the key phenotypic differences between species result primarily from alterations in the regulation of genes rather than in their sequences. To characterize gene expression patterns accross the brain and investigate the genetic basis of human specializations in brain organization and cognition, we used microarrays to quantify the transcript levels of thousands of genes in tissue samples from different brain regions of several human and chimpanzee individuals. Our results indicated that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans, and suggests that the human brain is characterized by elevated levels of neuronal activity. Experiment Overall Design: Gene-expression profiling was performed on 32 tissue samples from different brain regions of a total of 7 humans and 4 chimpanzees. Most samples were hybridized to a single independent arrays, but in a few cases 2 replicates from the same sample were performed, totaling 37 different arrays.
Project description:Accelerated brain development is a unique feature of the human species. Not only the size but also morphology, in particular the connections between frontal cortex and basal ganglia distinguish the human brain from great apes and other primates. Recent findings suggest that structural features which may be important for language acquisition are influenced by FOXP2, key regulator of CNTNAP2. CNTNAP2 is one of the largest genes in the chimpanzee genome, encompassing 2.5 Mb. It encodes a neurexin with essential roles in the vertebrate nervous system. The aim of our study was to compare the methylation patterns of CNTNAP2 in human and chimpanzee brains, assuming that epigenetic regulation is essential for brain development and human language abilities. To this end, we designed a NimbleGen tiling array covering the entire chimpanzee CNTNAP2 gene plus 0.1 Mb up- and downstream flanking sequence with an average resolution of 13 bp. Methylated DNA ImmunoPreciptation (MeDIP) was used to enrich cytosine-methylated DNA fragments for downstream analysis with high-resolution tiling arrays.
Project description:Accelerated brain development is a unique feature of the human species. Not only the size but also morphology, in particular the connections between frontal cortex and basal ganglia distinguish the human brain from great apes and other primates. Recent findings suggest that structural features which may be important for language acquisition are influenced by FOXP2, key regulator of CNTNAP2. CNTNAP2 is one of the largest genes in the chimpanzee genome, encompassing 2.5 Mb. It encodes a neurexin with essential roles in the vertebrate nervous system. The aim of our study was to compare the methylation patterns of CNTNAP2 in human and chimpanzee brains, assuming that epigenetic regulation is essential for brain development and human language abilities. To this end, we designed a NimbleGen tiling array covering the entire chimpanzee CNTNAP2 gene plus 0.1 Mb up- and downstream flanking sequence with an average resolution of 13 bp. Methylated DNA ImmunoPreciptation (MeDIP) was used to enrich cytosine-methylated DNA fragments for downstream analysis with high-resolution tiling arrays. MeDIP-based CNTNAP2 methylation profiling
Project description:Human Accelerated Regions (HARs) are highly conserved across species but exhibit a significant excess of human-specific sequence changes, suggesting they may have gained novel functions in human evolution. HARs include gene regulatory elements with human-specific activity and have been implicated in the evolution of the human brain. However, our understanding of how HARs contributed to uniquely human features of the brain is hindered by a lack of insight into the genes and pathways that HARs regulate. It is unknown whether HARs acted by altering the expression of gene targets conserved between HARs and their chimpanzee orthologs or by gaining new gene targets in human, a mechanism termed enhancer hijacking. We generated a high-resolution map of chromatin interactions for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs) to comprehensively identify gene targets in both species. HARs and their chimpanzee orthologs targeted a conserved set of 2,963 genes enriched for neurodevelopmental processes including neurogenesis and synaptic transmission. Changes in HAR enhancer activity were correlated with changes in conserved gene target expression. Conserved targets were enriched among genes differentially expressed between human and chimpanzee NSCs or between human and non-human primate developing and adult brain. Species-specific HAR gene targets did not converge on known biological functions and were not significantly enriched among differentially expressed genes, suggesting that most HARs did not alter gene expression via enhancer hijacking. HAR gene targets, including differentially expressed targets, also showed cell type-specific expression patterns in the developing human brain, notably in outer radial glia, which are hypothesized to contribute to human cortical expansion. Our findings support that HARs influenced human brain evolution by altering the expression of a conserved set of gene targets and provide the means to functionally link HARs with novel human brain features.
Project description:mRNA-seq were conducted for iPS cells of human-1 (409-B2/HPS0076), human-2 (Nips-B2/HPS0223), chimpanzee-1 (kiku/0138F-1), and chimpanzee-2 (mari/0274F-2). To compare gene expression levels, the reads were first mapped to the chimpanzee genome (panTro5), and mapped reads were then mapped to the human genome (hg38). Gene expression was anlyzed based on the hg38 annotation.