MicroRNA expression and regulation in human, chimpanzee, and macaque brain
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PROVIDER: PRJNA136625 | ENA |
REPOSITORIES: ENA
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Project description:Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence between adult humans, chimpanzees and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using combination of high-throughput sequencing, miRNA microarrays and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% - between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2-4% of mRNA and 4-6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA-driven regulation on the human evolutionary lineage, were further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions. Human, chimpanzee, and rhesus: mRNA, microRNA, and microRNA sequencing. Neuroblastoma cell lines: miRNA transfection experiments were conducted on two human-derived neuroblastoma cell lines (SH-SY5Y and SK-N-SH). Briefly, cells were plated in 0.5ml of growth medium, without antibiotics, 24h prior to transfection. miRNA mimics-Lipofectamine 2000 (Invitrogen) complexes were prepared freshly before transfection according to the manufacturer's protocol. SH-SY5Y and SK-N-SH cells were transfected in six-well plates using miRNA mimics-Lipofectamine 2000 with a final oligonucleotide concentration of 10nmol/L. In parallel, negative control transfections with mock oligonucleotides were conducted according to the manufacturer's protocol. For each cell line, transfections with negative control oligonucleotides were carried out in two independent replicates. Cells were harvested after 24h, total RNA were extracted with Trizol reagent (Invitrogen) and further processed and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays following the manufacturer's instructions. The gene expression levels were determined using rma in the R Affy package.
2011-10-17 | E-GEOD-26545 | biostudies-arrayexpress
Project description:Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence between adult humans, chimpanzees and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using combination of high-throughput sequencing, miRNA microarrays and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% - between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2-4% of mRNA and 4-6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA-driven regulation on the human evolutionary lineage, were further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions.
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Project description:We performed deep strand-specific sequencing of poly-adenylated RNA (polyA+ RNAseq) from human, chimpanzee, macaque and mouse tissues, with the goal of detecting numerous non-annotated poorly expressed and antisense genes. We identified thousands of annotated and novel genes, especially in testis. We discovered that ~2% of the human and chimpanzee multiexonic genes were specific from such species.
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Project description:we used RNA-Seq to quantify the RNA editing level at more than 8,000 previously annotated exonic A-to-I RNA editing sites in two brain regions - prefrontal cortex and cerebellum - of humans, chimpanzees and rhesus macaques. We observed substantial conservation of RNA editing levels between the brain regions, as well as among the three primate species. Evolutionary changes in RNA editing were nonetheless evident among the species. Across lifespan, we observed an increase of the RNA editing level with advanced age in both brain regions of all three primate species. poly(A) enriched RNAs extracted from pooled samples of two brain regions: CBC and PFC of chimpanzee and macaque, fragmented, revers transcribed to double-stranded cDNA using random hexamers. Sequencing libraries were prepared according to the paired-end non-strand-specific sample preparation protocol of Illumina. Each sample was sequenced in a separate lane in the Illumina Genome Analyzer II system, using the 75-bp paired-end sequencing protocol. human data was downloaded from SRA [SRP005169]
2014-01-07 | E-GEOD-45244 | biostudies-arrayexpress
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Project description:We identified human-specific gene expression patterns in the brain by comparing expression with chimpanzee and rhesus macaque. DpnII tag-based libraries were generated from human, chimpanzee, and rhesus macaque brain (frontal pole, hippocampus, caudate nucleus), and sequenced using an Illumina Genome Analyzer.
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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).
2015-06-19 | GSE38804 | GEO
Project description:While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such change remain poorly understood. Here we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA) expression in two brain regions within macaques, chimpanzees and humans throughout their lifespan. We find that developmental profiles of trans-regulators, such as miRNA, as well as their target genes, show the fastest rates of human-specific evolutionary change. Changes in expression of a few key regulators may be a major driving force behind human brain evolution. Human, chimpanzee and rhesus macaque post-mortem brain samples from the prefrontal cortex and cerebellar cortex were collected. The age ranges of the individuals in all three species covered the respective species' postnatal maturation period from infancy to old adulthood. RNA extracted from the dissected tissue was hybridized to B72.
2011-12-09 | E-GEOD-29356 | biostudies-arrayexpress
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)
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