Alzheimer-related genes show accelerated evolution
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA575233 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-01-19 | GSE138261 | GEO
Project description:Alzheimer's disease (AD) is a neurodegenerative disorder of unknown cause with complex genetic and environmental traits. While AD is extremely prevalent in human elderly, it hardly occurs in non-primate mammals and even non-human-primates develop only an incomplete form of the disease. This specificity of AD to human clearly implies a phylogenetic aspect. Still, the evolutionary dimension of AD pathomechanism remains difficult to prove and has not been established so far. To analyze the evolutionary age and dynamics of AD-associated-genes, we established the AD-associated genome-wide RNA-profile comprising both protein-coding and non-protein-coding transcripts. We than applied a systematic analysis on the conservation of splice-sites as a measure of gene-structure based on multiple alignments across vertebrates of homologs of AD-associated-genes. Here, we show that nearly all AD-associated-genes are evolutionarily old and did not originate later in evolution than not-AD-associated-genes. However, the gene-structures of loci, that exhibit AD-associated changes in their expression, evolve faster than the genome at large. While protein-coding-loci exhibit an enhanced rate of small changes in gene structure, non-coding loci show even much larger changes. The accelerated evolution of AD-associated-genes indicates a more rapid functional adaptation of these genes. In particular AD-associated non-coding-genes play an important, as yet largely unexplored, role in AD. This phylogenetic trait indicates that recent adaptive evolution of human brain is causally involved in basic principles of neurodegeneration. It highlights the necessity for a paradigmatic change of our disease-concepts and to reconsider the appropriateness of current animal-models to develop disease-modifying strategies that can be translated to human.
| S-EPMC8758480 | biostudies-literature
Project description:Long noncoding RNA sequences evolve relatively rapidly, but it is unclear whether this is due to relaxed constraint or accelerated evolution. Here, we trace the recent evolutionary history of human lncRNAs, using genomes of multiple individuals from all great ape species to map fixed lineage-specific nucleotide variants. We find that the lower conservation of lncRNAs compared to protein coding genes partially arises from lncRNA’s more recent evolutionary origin. We identify more than one hundred lncRNAs that show some evidence of accelerated evolution in at least one primate species, including 17 in human. Several of these display transcriptional regulatory activity in an RNA-specific reporter assay. By experimentally reconstructing the ancestral lncRNA sequence, we find that this activity has been altered by human-specific nucleotide substitutions. Functional analysis of accelerated lncRNAs with specific expression in blood suggests lncRNAs have participated in adaptive regulatory changes in the immune system during recent human evolution. Together our results provide evidence that accelerated evolution of lncRNAs may have contributed, through regulatory changes, to human-specific phenotypes.
2018-11-30 | GSE80554 | GEO
Project description:Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in oligodendrocytes and show that oligodendrocytes have undergone accelerated gene expression evolution in the human lineage. The signature of acceleration is enriched for cell type-specific expression alterations in schizophrenia. These results underscore the importance of oligodendrocytes in human brain evolution.
2019-12-31 | GSE123936 | GEO
Project description:Sexually dimorphic traits are subject to diversifying selection. Also genes with a male biased gene expression are probably affected by sexual selection and have a high rate of protein evolution. We used SAGE to measure sex biased gene expression in Drosophila pseudoobscura. Consistent with previous results from D. melanogaster, a larger number of genes were male biased (402 genes) than female biased (138 genes). About 34% of the genes changed the sex related expression pattern between D. melanogaster and D. pseudoobscura. Combining gene expression with protein divergence between both species, we observed a striking difference in rate of evolution for genes with a male biased gene expression in one species only. Contrary to expectations, D. pseudoobscura genes in this category showed no accelerated rate of protein evolution, while D. melanogaster genes did. If sexual selection is driving molecular evolution of male biased genes, our data imply a radically different selection regime in D. pseudoobscura. Keywords: SAGE Male and female SAGE libraries of D. pseudoobscura were developed for analyzing the gene expression pattern.
2006-07-27 | E-GEOD-2840 | biostudies-arrayexpress
Project description:Accelerated evolution of oligodendrocytes in human brain
| PRJNA510347 | ENA
Project description:Sexually dimorphic traits are subject to diversifying selection. Also genes with a male biased gene expression are probably affected by sexual selection and have a high rate of protein evolution. We used SAGE to measure sex biased gene expression in Drosophila pseudoobscura. Consistent with previous results from D. melanogaster, a larger number of genes were male biased (402 genes) than female biased (138 genes). About 34% of the genes changed the sex related expression pattern between D. melanogaster and D. pseudoobscura. Combining gene expression with protein divergence between both species, we observed a striking difference in rate of evolution for genes with a male biased gene expression in one species only. Contrary to expectations, D. pseudoobscura genes in this category showed no accelerated rate of protein evolution, while D. melanogaster genes did. If sexual selection is driving molecular evolution of male biased genes, our data imply a radically different selection regime in D. pseudoobscura. Keywords: SAGE
2006-07-27 | GSE2840 | GEO
Project description:Transient genomic instability drives tumorigenesis through accelerated clonal evolution
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Project description:The genetic bases underlying the evolution of morphological and functional innovations of the mammalian inner ear are poorly understood. Gene regulatory regions are thought to play an important role in the evolution of form and function. To uncover crucial hearing genes whose regulatory machinery evolved specifically in mammalian lineages, we mapped accelerated noncoding sequences (ACNEs) in inner ear transcription factors (TFs) identifying PKNOX2 as the gene displaying the largest amount of ACNEs. To investigate the function of PKNOX2-ACNEs, we tested them using enhancer assays in transgenic zebrafish and unmasked transcriptional enhancers that acquired novel expression patterns as a consequence of the evolutionary process they underwent. Even though PKNOX2 is one of the most highly expressed genes in cochlear hair cells, its function was unknown. Thus, to explore the role of PKNOX2 in mammalian hearing, we generated Pknox2 null mice using CRISPR/Cas9 technology. Pknox2-/- mice exhibited reduced distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) thresholds at high frequencies together with an increase in peak 1 amplitude, consistent with a higher number of IHCs-auditory nerve synapsis observed at the cochlear basal region. A comprehensive cochlear transcriptomic analysis of Pknox2-/- and Pknox2+/+ mice revealed that key auditory genes are under Pknox2 control. Hence, we report, for the first time, that PKNOX2 has a critical function regulating cochlear sensitivity at higher frequencies and that its regulatory machinery underwent lineage-specific evolution, providing novel insight into the contribution of this TF to normal auditory function and to the evolution of high-frequency hearing.
2023-06-01 | GSE171921 | GEO