ArticleGenome biology2021
Evolutionary conservation and divergence of the human brain transcriptome.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 95 citations in OpenAlex.
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- A General Principle of Neuronal Evolution Reveals a Human-Accelerated Neuron Type Potentially Underlying the High Prevalence of Autism in Humans.Molecular biology and evolution · 2025Article
- β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity.Molecular neurodegeneration · 2025Article
- Systematical Comparison Reveals Distinct Brain Transcriptomic Characteristics in Depression Models Induced by Gut Microbiota Dysbiosis and Chronic Stress.Molecular neurobiology · 2025Article
- Neuronal growth patterns and synapse formation are mediated by distinct activity-dependent mechanisms.Scientific reports · 2025Article
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- Benchmarking macaque brain gene expression for horizontal and vertical translation.Science advances · 2025Article
- Cross-species imputation and comparison of single-cell transcriptomic profiles.Genome biology · 2025Article
- A general principle of neuronal evolution reveals a human-accelerated neuron type potentially underlying the high prevalence of autism in humans.bioRxiv : the preprint server for biology · 2025Article
- Exploring the therapeutic potential of psychedelics: Fear extinction mechanisms and amygdala modulation.Psychedelics · 2025Article
- Exploring the Expanded Role of Astrocytes in Primate Brain Evolution via Changes in Gene Expression.Brain, behavior and evolution · 2025Review
- Inhibitory Systems in Brain Evolution: Pathways of Vulnerability in Neurodevelopmental Disorders.Brain, behavior and evolution · 2025Review
- ER and SOCE CaCell calcium · 2024Article
- Cross-species imputation and comparison of single-cell transcriptomic profiles.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMouse models have allowed for the direct interrogation of genetic effects on molecular, physiological, and behavioral brain phenotypes. However, it is unknown to what extent neurological or psychiatric traits may be human- or primate-specific and therefore which components can be faithfully recapitulated in mouse models.
resultsWe compare conservation of co-expression in 116 independent data sets derived from human, mouse, and non-human primate representing more than 15,000 total samples. We observe greater changes occurring on the human lineage than mouse, and substantial regional variation that highlights cerebral cortex as the most diverged region. Glia, notably microglia, astrocytes, and oligodendrocytes are the most divergent cell type, three times more on average than neurons. We show that cis-regulatory sequence divergence explains a significant fraction of co-expression divergence. Moreover, protein coding sequence constraint parallels co-expression conservation, such that genes with loss of function intolerance are enriched in neuronal, rather than glial modules. We identify dozens of human neuropsychiatric and neurodegenerative disease risk genes, such as COMT, PSEN-1, LRRK2, SHANK3, and SNCA, with highly divergent co-expression between mouse and human and show that 3D human brain organoids recapitulate in vivo co-expression modules representing several human cell types.
conclusionsWe identify robust co-expression modules reflecting whole-brain and regional patterns of gene expression. Compared with those that represent basic metabolic processes, cell-type-specific modules, most prominently glial modules, are the most divergent between species. These data and analyses serve as a foundational resource to guide human disease modeling and its interpretation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.