Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Liu, Xiling
Somel, Mehmet
Tang, Lin
Yan, Zheng
Jiang, Xi
Guo, Song
Yuan, Yuan
He, Liu
Oleksiak, Anna
Zhang, Yan
Li, Na
Hu, Yuhui
Chen, Wei
Qiu, Zilong
Paeaebo, Svante
Khaitovich, Philipp
Over the course of ontogenesis, the human brain and human cognitive abilities develop in parallel, resulting in a phenotype strikingly distinct from that of other primates. Here, we used microarrays and RNA-sequencing to examine human-specific gene expression changes taking place during postnatal brain development in the prefrontal cortex and cerebellum of humans, chimpanzees, and rhesus macaques. We show that the most prominent human-specific expression change affects genes associated with synaptic functions and represents an extreme shift in the timing of synaptic development in the prefrontal cortex, but not the cerebellum. Consequently, peak expression of synaptic genes in the prefrontal cortex is shifted from <1 yr in chimpanzees and macaques to 5 yr in humans. This result was supported by protein expression profiles of synaptic density markers and by direct observation of synaptic density by electron microscopy. Mechanistically, the human-specific change in timing of synaptic development involves the MEF2A-mediated activity-dependent regulatory pathway. Evolutionarily, this change may have taken place after the split of the human and the Neanderthal lineages.


Rapid metabolic evolution in human prefrontal cortex
Fu, Xing; Giavalisco, Patrick; Liu, Xiling; Catchpole, Gareth; Fu, Ning; Ning, Zhi-Bin; Guo, Song; Yan, Zheng; Somel, Mehmet; Paeaebo, Svante; Zeng, Rong; Willmitzer, Lothar; Khaitovich, Philipp (2011-04-12)
Human evolution is characterized by the rapid expansion of brain size and drastic increase in cognitive capabilities. It has long been suggested that these changes were accompanied by modifications of brain metabolism. Indeed, human-specific changes on gene expression or amino acid sequence were reported for a number of metabolic genes, but actual metabolite measurements in humans and apes have remained scarce. Here, we investigate concentrations of more than 100 metabolites in the prefrontal and cerebellar...
MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates
Somel, Mehmet; Tang, Lin; Yan, Zheng; Hu, Haiyang; Guo, Song; Jiang, Xi; Zhang, Xiaoyu; Xu, Guohua; Xie, Gangcai; Li, Na; Hu, Yuhui; Chen, Wei; Paeaebo, Svante; Khaitovich, Philipp (2011-12-01)
While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such changes are unknown. 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 constitutive gene expression divergence (species differences independent of age) is comparable between humans and chimpanzees. However, ...
Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony
Somel, Mehmet; Liu, Xiling (Elsevier BV, 2014-12-01)
Primate brain transcriptome comparisons within the last 12 years have yielded interesting but contradictory observations on how the transcriptome evolves, and its adaptive role in human cognitive evolution. Since the human-chimpanzee common ancestor, the human prefrontal cortex transcriptome seems to have evolved more than that of the chimpanzee. But at the same time, most expression differences among species, especially those observed in adults, appear as consequences of neutral evolution at cis-regulatory...
Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism
Liu, Xiling; Han, Dingding; Somel, Mehmet; Jiang, Xi; Hui, Haiyang; Guijarro, Patricia; Zhang, Ning; Mitchell, Amanda; Halene, Tobias; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Paeaebo, Svante; Akbarian, Schahram; Khaitovich, Philipp (2016-09-01)
Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in...
Emergence of verb and object concepts through learning affordances
Dağ, Nilgün; Kalkan, Sinan; Şahin, Erol; Department of Computer Engineering (2010)
Researchers are still far from thoroughly understanding and building accurate computational models of the mechanisms in human mind that give rise to cognitive processes such as emergence of concepts and language acquisition. As a new attempt to give an insight into this issue, in this thesis, we are concerned about developing a computational model that leads to the emergence of concepts. Speci cally, we investigate how a robot can acquire verb and object concepts through learning affordances, a notion first...
Citation Formats
X. Liu et al., “Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques,” GENOME RESEARCH, pp. 611–622, 2012, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/42447.