RESUMO
Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether human cells exhibit distinct genetic dependencies. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferation. These genes comprised coherent processes, including cell-cycle progression and lysosomal signaling, which we determined to be human-derived by comparison with orangutan cells. Human-specific robustness to CDK2 and CCNE1 depletion persisted in neural progenitor cells and cerebral organoids, supporting the G1-phase length hypothesis as a potential evolutionary mechanism in human brain expansion. Our findings demonstrate that evolutionary changes in human cells reshaped the landscape of essential genes and establish a platform for systematically uncovering latent cellular and molecular differences between species.
Assuntos
Hominidae , Células-Tronco Neurais , Células-Tronco Pluripotentes , Células-Tronco , Animais , Humanos , Pan troglodytes/genéticaRESUMO
The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.
Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Imunidade nas Mucosas , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Citocinas/sangue , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Vetores Genéticos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Testes de Neutralização , Nucleocapsídeo/genética , Nucleocapsídeo/imunologia , Nucleocapsídeo/metabolismo , Pan troglodytes , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced by monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect in passive transfer experiments, mucosal antibody and cross-reactive memory T cell responses were robust, and protection was evident against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in mice and hamsters. However, depletion of memory CD8+ T cells before XBB.1.5 challenge resulted in loss of protection against upper and lower respiratory tract infection. Thus, nasally delivered vaccines stimulate mucosal immunity against emerging SARS-CoV-2 strains, and cross-reactive memory CD8+ T cells mediate protection against lung infection by antigenically distant strains in the setting of low serum levels of cross-reactive neutralizing antibodies.
Assuntos
COVID-19 , Infecções Respiratórias , Vacinas , Cricetinae , Animais , Camundongos , Linfócitos T CD8-Positivos , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Anticorpos Amplamente Neutralizantes , Pan troglodytesRESUMO
The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla, and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that neuroepithelial differentiation is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition, associated with differences in interkinetic nuclear migration and cell cycle length. Comparative RNA sequencing (RNA-seq) reveals differences in expression dynamics of cell morphogenesis factors, including ZEB2, a known epithelial-mesenchymal transition regulator. We show that ZEB2 promotes neuroepithelial transition, and its manipulation and downstream signaling leads to acquisition of nonhuman ape architecture in the human context and vice versa, establishing an important role for neuroepithelial cell shape in human brain expansion.
Assuntos
Evolução Biológica , Encéfalo/citologia , Forma Celular/fisiologia , Animais , Encéfalo/metabolismo , Diferenciação Celular , Linhagem Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Transição Epitelial-Mesenquimal/genética , Expressão Gênica , Gorilla gorilla , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Neurogênese , Neurônios/citologia , Neurônios/metabolismo , Organoides/citologia , Organoides/metabolismo , Pan troglodytes , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismoRESUMO
In a recent issue of Nature, Kanton et al. explore human brain evolution and development by profiling the single-cell transcriptomes and epigenomes of cerebral organoids derived from human, chimpanzee, and macaque stem cells. Their results reveal key molecular characteristics that differentiate humans and non-human primates at the earliest stages of brain development.
Assuntos
Genômica , Organoides , Animais , Encéfalo , Humanos , Pan troglodytes , TranscriptomaRESUMO
Denisovans are an extinct group of humans whose morphology remains unknown. Here, we present a method for reconstructing skeletal morphology using DNA methylation patterns. Our method is based on linking unidirectional methylation changes to loss-of-function phenotypes. We tested performance by reconstructing Neanderthal and chimpanzee skeletal morphologies and obtained >85% precision in identifying divergent traits. We then applied this method to the Denisovan and offer a putative morphological profile. We suggest that Denisovans likely shared with Neanderthals traits such as an elongated face and a wide pelvis. We also identify Denisovan-derived changes, such as an increased dental arch and lateral cranial expansion. Our predictions match the only morphologically informative Denisovan bone to date, as well as the Xuchang skull, which was suggested by some to be a Denisovan. We conclude that DNA methylation can be used to reconstruct anatomical features, including some that do not survive in the fossil record.
Assuntos
Metilação de DNA/genética , Homem de Neandertal/anatomia & histologia , Homem de Neandertal/genética , Pan troglodytes/anatomia & histologia , Pan troglodytes/genética , Fenótipo , Animais , Sequência de Bases , Bases de Dados Genéticas , Extinção Biológica , Fósseis , Genoma Humano/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Esqueleto , CrânioRESUMO
Direct comparisons of human and non-human primate brains can reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is inaccessible during neocortical neurogenesis when differences in brain size first appear. To identify human-specific features of cortical development, we leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee. Despite metabolic differences, organoid models preserve gene regulatory networks related to primary cell types and developmental processes. We further identified 261 differentially expressed genes in human compared to both chimpanzee organoids and macaque cortex, enriched for recent gene duplications, and including multiple regulators of PI3K-AKT-mTOR signaling. We observed increased activation of this pathway in human radial glia, dependent on two receptors upregulated specifically in human: INSR and ITGB8. Our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.
Assuntos
Córtex Cerebral/citologia , Organoides/metabolismo , Animais , Evolução Biológica , Encéfalo/citologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular/genética , Córtex Cerebral/metabolismo , Redes Reguladoras de Genes/genética , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Macaca , Neurogênese/genética , Organoides/crescimento & desenvolvimento , Pan troglodytes , Células-Tronco Pluripotentes/citologia , Análise de Célula Única , Especificidade da Espécie , Transcriptoma/genéticaRESUMO
Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and is a determinant of neuronal number in the mammalian cortex. We find that three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Functional analysis reveals that different alleles of NOTCH2NL have varying potencies to enhance Notch signaling by interacting directly with NOTCH receptors. Consistent with a role in Notch signaling, NOTCH2NL ectopic expression delays differentiation of neuronal progenitors, while deletion accelerates differentiation into cortical neurons. Furthermore, NOTCH2NL genes provide the breakpoints in 1q21.1 distal deletion/duplication syndrome, where duplications are associated with macrocephaly and autism and deletions with microcephaly and schizophrenia. Thus, the emergence of human-specific NOTCH2NL genes may have contributed to the rapid evolution of the larger human neocortex, accompanied by loss of genomic stability at the 1q21.1 locus and resulting recurrent neurodevelopmental disorders.
Assuntos
Encéfalo/embriologia , Córtex Cerebral/fisiologia , Neurogênese/fisiologia , Receptor Notch2/metabolismo , Transdução de Sinais , Animais , Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Feminino , Deleção de Genes , Genes Reporter , Gorilla gorilla , Células HEK293 , Humanos , Neocórtex/citologia , Células-Tronco Neurais/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Pan troglodytes , Receptor Notch2/genética , Análise de Sequência de RNARESUMO
Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution.
Assuntos
DNA/metabolismo , Proteínas Nucleares/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Proteínas de Transporte/química , Proteínas de Transporte/classificação , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , DNA/química , Humanos , Fator de Crescimento Insulin-Like II/química , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Camundongos , Simulação de Dinâmica Molecular , Proteínas Nucleares/química , Proteínas Nucleares/classificação , Proteínas Nucleares/genética , Conformação de Ácido Nucleico , Pan troglodytes , Filogenia , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Alinhamento de SequênciaRESUMO
LINE retrotransposons actively shape mammalian genomes. Denli et al. reveal a new open reading frame, ORF0, on the antisense strand of human LINE-1 encoding a small regulatory protein. This finding may represent the birth of an emerging retrotransposon gene that can adopt various fates, as it can be fused to adjacent host sequences.
Assuntos
Pan troglodytes/genética , Retroelementos , Animais , HumanosRESUMO
Prescott et al. take a step forward in studying primate morphological evolution by a cellular anthropology approach. Through epigenomic profiling of in-vitro-derived cells, the authors identify and characterize candidate cis-regulatory elements underlying divergence in facial morphology between human and chimp, shedding new light on what makes us (look) human.
Assuntos
Epigenômica/métodos , Evolução Molecular , Melhoramento Genético , Crista Neural/citologia , Pan troglodytes/genética , Animais , HumanosRESUMO
cis-regulatory changes play a central role in morphological divergence, yet the regulatory principles underlying emergence of human traits remain poorly understood. Here, we use epigenomic profiling from human and chimpanzee cranial neural crest cells to systematically and quantitatively annotate divergence of craniofacial cis-regulatory landscapes. Epigenomic divergence is often attributable to genetic variation within TF motifs at orthologous enhancers, with a novel motif being most predictive of activity biases. We explore properties of this cis-regulatory change, revealing the role of particular retroelements, uncovering broad clusters of species-biased enhancers near genes associated with human facial variation, and demonstrating that cis-regulatory divergence is linked to quantitative expression differences of crucial neural crest regulators. Our work provides a wealth of candidates for future evolutionary studies and demonstrates the value of "cellular anthropology," a strategy of using in-vitro-derived embryonic cell types to elucidate both fundamental and evolving mechanisms underlying morphological variation in higher primates.
Assuntos
Epigenômica/métodos , Evolução Molecular , Melhoramento Genético , Crista Neural/citologia , Pan troglodytes/genética , Animais , Embrião de Mamíferos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Camundongos Transgênicos , Crista Neural/metabolismo , Especificidade da EspécieRESUMO
LINE-1 retrotransposons are fast-evolving mobile genetic entities that play roles in gene regulation, pathological conditions, and evolution. Here, we show that the primate LINE-1 5'UTR contains a primate-specific open reading frame (ORF) in the antisense orientation that we named ORF0. The gene product of this ORF localizes to promyelocytic leukemia-adjacent nuclear bodies. ORF0 is present in more than 3,000 loci across human and chimpanzee genomes and has a promoter and a conserved strong Kozak sequence that supports translation. By virtue of containing two splice donor sites, ORF0 can also form fusion proteins with proximal exons. ORF0 transcripts are readily detected in induced pluripotent stem (iPS) cells from both primate species. Capped and polyadenylated ORF0 mRNAs are present in the cytoplasm, and endogenous ORF0 peptides are identified upon proteomic analysis. Finally, ORF0 enhances LINE-1 mobility. Taken together, these results suggest a role for ORF0 in retrotransposon-mediated diversity.
Assuntos
Pan troglodytes/genética , Retroelementos , Regiões 5' não Traduzidas , Sequência de Aminoácidos , Animais , Sequência de Bases , Citoplasma/genética , Humanos , Elementos Nucleotídeos Longos e Dispersos , Dados de Sequência Molecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Fases de Leitura Aberta , Processamento Pós-Transcricional do RNA , RNA Antissenso/genética , RNA Mensageiro/química , RNA Mensageiro/genética , Ribossomos/metabolismo , Alinhamento de SequênciaRESUMO
Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size1. As a result, patterns of human centromeric variation and models for their evolution and function remain incomplete, despite centromeres being among the most rapidly mutating regions2,3. Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome4,5. We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks and vary up to 3-fold in size. Moreover, we find that 45.8% of centromeric sequence cannot be reliably aligned using standard methods owing to the emergence of new α-satellite higher-order repeats (HORs). DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by >500 kb. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan and macaque genomes. Comparative analyses reveal a nearly complete turnover of α-satellite HORs, with characteristic idiosyncratic changes in α-satellite HORs for each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the short (p) and long (q) arms across centromeres and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.
Assuntos
Centrômero , Evolução Molecular , Variação Genética , Animais , Humanos , Centrômero/genética , Centrômero/metabolismo , Proteína Centromérica A/metabolismo , Metilação de DNA/genética , DNA Satélite/genética , Cinetocoros/metabolismo , Macaca/genética , Pan troglodytes/genética , Polimorfismo de Nucleotídeo Único/genética , Pongo/genética , Masculino , Feminino , Padrões de Referência , Imunoprecipitação da Cromatina , Haplótipos , Mutação , Amplificação de Genes , Alinhamento de Sequência , Cromatina/genética , Cromatina/metabolismo , Especificidade da EspécieRESUMO
Apes possess two sex chromosomes-the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility1. The X chromosome is vital for reproduction and cognition2. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements-owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.
Assuntos
Hominidae , Cromossomo X , Cromossomo Y , Animais , Feminino , Masculino , Gorilla gorilla/genética , Hominidae/genética , Hominidae/classificação , Hylobatidae/genética , Pan paniscus/genética , Pan troglodytes/genética , Filogenia , Pongo abelii/genética , Pongo pygmaeus/genética , Telômero/genética , Cromossomo X/genética , Cromossomo Y/genética , Evolução Molecular , Variações do Número de Cópias de DNA/genética , Humanos , Espécies em Perigo de Extinção , Padrões de ReferênciaRESUMO
Salmonella Typhi is an exclusive human pathogen that causes typhoid fever. Typhoid toxin is a S. Typhi virulence factor that can reproduce most of the typhoid fever symptoms in experimental animals. Toxicity depends on toxin binding to terminally sialylated glycans on surface glycoproteins. Human glycans are unusual because of the lack of CMAH, which in other mammals converts N-acetylneuraminic acid (Neu5Ac) to N-glycolylneuraminic acid (Neu5Gc). Here, we report that typhoid toxin binds to and is toxic toward cells expressing glycans terminated in Neu5Ac (expressed by humans) over glycans terminated in Neu5Gc (expressed by other mammals). Mice constitutively expressing CMAH thus displaying Neu5Gc in all tissues are resistant to typhoid toxin. The atomic structure of typhoid toxin bound to Neu5Ac reveals the structural bases for its binding specificity. These findings provide insight into the molecular bases for Salmonella Typhi's host specificity and may help the development of therapies for typhoid fever.
Assuntos
Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Glicoproteínas de Membrana/química , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/metabolismo , Salmonella typhi/química , Animais , Toxinas Bacterianas/genética , Linhagem Celular , Células Cultivadas , Cristalografia por Raios X , Especificidade de Hospedeiro , Humanos , Células Jurkat , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Ácidos Neuramínicos/metabolismo , Pan troglodytes , Salmonella typhi/patogenicidade , Febre Tifoide/microbiologiaRESUMO
The naming of Australopithecus africanus in 1925, based on the Taung Child, heralded a new era in human evolutionary studies and turned the attention of the then Eurasian-centric palaeoanthropologists to Africa, albeit with reluctance. Almost one hundred years later, Africa is recognized as the cradle of humanity, where the entire evolutionary history of our lineage prior to two million years ago took place-after the Homo-Pan split. This Review examines data from diverse sources and offers a revised depiction of the genus and characterizes its role in human evolution. For a long time, our knowledge of Australopithecus came from both A. africanus and Australopithecus afarensis, and the members of this genus were portrayed as bipedal creatures that did not use stone tools, with a largely chimpanzee-like cranium, a prognathic face and a brain slightly larger than that of chimpanzees. Subsequent field and laboratory discoveries, however, have altered this portrayal, showing that Australopithecus species were habitual bipeds but also practised arboreality; that they occasionally used stone tools to supplement their diet with animal resources; and that their infants probably depended on adults to a greater extent than what is seen in apes. The genus gave rise to several taxa, including Homo, but its direct ancestor remains elusive. In sum, Australopithecus had a pivotal bridging role in our evolutionary history owing to its morphological, behavioural and temporal placement between the earliest archaic putative hominins and later hominins-including the genus Homo.
Assuntos
Evolução Biológica , Hominidae , Animais , Humanos , Fósseis , Hominidae/anatomia & histologia , Hominidae/classificação , Pan troglodytes/anatomia & histologia , Pan troglodytes/classificação , Crânio/anatomia & histologia , Comportamento de Utilização de Ferramentas , EnvelhecimentoRESUMO
Human-specific genomic changes contribute to the unique functionalities of the human brain1-5. The cellular heterogeneity of the human brain6,7 and the complex regulation of gene expression highlight the need to characterize human-specific molecular features at cellular resolution. Here we analysed single-nucleus RNA-sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing datasets for human, chimpanzee and rhesus macaque brain tissue from posterior cingulate cortex. We show a human-specific increase of oligodendrocyte progenitor cells and a decrease of mature oligodendrocytes across cortical tissues. Human-specific regulatory changes were accelerated in oligodendrocyte progenitor cells, and we highlight key biological pathways that may be associated with the proportional changes. We also identify human-specific regulatory changes in neuronal subtypes, which reveal human-specific upregulation of FOXP2 in only two of the neuronal subtypes. We additionally identify hundreds of new human accelerated genomic regions associated with human-specific chromatin accessibility changes. Our data also reveal that FOS::JUN and FOX motifs are enriched in the human-specifically accessible chromatin regions of excitatory neuronal subtypes. Together, our results reveal several new mechanisms underlying the evolutionary innovation of human brain at cell-type resolution.
Assuntos
Evolução Molecular , Giro do Cíngulo , Animais , Humanos , Núcleo Celular/metabolismo , Cromatina/genética , Cromatina/metabolismo , Conjuntos de Dados como Assunto , Genoma Humano/genética , Genômica , Giro do Cíngulo/citologia , Giro do Cíngulo/metabolismo , Macaca mulatta/genética , Neurônios/classificação , Neurônios/citologia , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Pan troglodytes/genética , Análise da Expressão Gênica de Célula Única , Células-Tronco/citologia , Transposases/metabolismo , Montagem e Desmontagem da CromatinaRESUMO
Long-standing questions about human brain evolution may only be resolved through comparisons with close living evolutionary relatives, such as chimpanzees. This applies in particular to structural white matter (WM) connectivity, which continuously expanded throughout evolution. However, due to legal restrictions on chimpanzee research, neuroscience research currently relies largely on data with limited detail or on comparisons with evolutionarily distant monkeys. Here, we present a detailed magnetic resonance imaging resource to study structural WM connectivity in the chimpanzee. This open-access resource contains (1) WM reconstructions of a postmortem chimpanzee brain, using the highest-quality diffusion magnetic resonance imaging data yet acquired from great apes; (2) an optimized and validated method for high-quality fiber orientation reconstructions; and (3) major fiber tract segmentations for cross-species morphological comparisons. This dataset enabled us to identify phylogenetically relevant details of the chimpanzee connectome, and we anticipate that it will substantially contribute to understanding human brain evolution.