Human Evolution: Enhancing the Brain

Enard, Wolfgang

doi:10.1016/j.cub.2015.03.031

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Finally, because gene regulation has diverged significantly between primates and model organisms such as mice, zebrafish or flies, it is hard to test hypotheses about the functional effects of regulatory mutations. In this review, we discuss advances to address these barriers with an emphasis on linking sequence to function, complementing other recent papers that explore genetic and regulatory changes in human evolution [ 8 – 13 ].…”

Section: Post-genomic Challenges For Determining Uniquely Human Biolomentioning

confidence: 99%

Human evolution: the non-coding revolution

Franchini

Pollard

2017

BMC Biol

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What made us human? Gene expression changes clearly played a significant part in human evolution, but pinpointing the causal regulatory mutations is hard. Comparative genomics enabled the identification of human accelerated regions (HARs) and other human-specific genome sequences. The major challenge in the past decade has been to link diverged sequences to uniquely human biology. This review discusses approaches to this problem, progress made at the molecular level, and prospects for moving towards genetic causes for uniquely human biology.

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Section: Post-genomic Challenges For Determining Uniquely Human Biolomentioning

confidence: 99%

Human evolution: the non-coding revolution

Franchini

Pollard

2017

BMC Biol

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“…ens neanderthalensis, which is the hominid with the biggest brain size [1,2]. Brain development is a dynamic process that requires a complex molecular network to coordinate the genesis of specific cell types, the maintenance and homeostasis of stem cells, and the wiring of different cells within the brain structure.…”

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confidence: 99%

The DNA damage response molecule MCPH1 in brain development and beyond

Liu¹,

Zhou²,

Wang³

2016

ABBS

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Microcephalin (MCPH1) is identified as being responsible for the neurodevelopmental disorder primary microcephaly type 1, which is characterized by a smaller-than-normal brain size and mental retardation. MCPH1 has originally been identified as an important regulator of telomere integrity and of cell cycle control. Genetic and cellular studies show that MCPH1 controls neurogenesis by coordinating the cell cycle and the centrosome cycle and thereby regulating the division mode of neuroprogenitors to prevent the exhaustion of the progenitor pool and thereby microcephaly. In addition to its role in neurogenesis, MCPH1 plays a role in gonad development. MCPH1 also functions as a tumor suppressor in several human cancers as well as in mouse models. Here, we review the role of MCPH1 in DNA damage response, cell cycle control, chromosome condensation and chromatin remodeling. We also summarize the studies on the biological functions of MCPH1 in brain size determination and in pathologies, including infertility and cancer.

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Species-Specific Changes in a Primate Transcription Factor Network Provide Insights into the Molecular Evolution of the Primate Prefrontal Cortex

Berto

Nowick

2018

Genome Biology and Evolution

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The human prefrontal cortex (PFC) differs from that of other primates with respect to size, histology, and functional abilities. Here, we analyzed genome-wide expression data of humans, chimpanzees, and rhesus macaques to discover evolutionary changes in transcription factor (TF) networks that may underlie these phenotypic differences. We determined the co-expression networks of all TFs with species-specific expression including their potential target genes and interaction partners in the PFC of all three species. Integrating these networks allowed us inferring an ancestral network for all three species. This ancestral network as well as the networks for each species is enriched for genes involved in forebrain development, axonogenesis, and synaptic transmission. Our analysis allows us to directly compare the networks of each species to determine which links have been gained or lost during evolution. Interestingly, we detected that most links were gained on the human lineage, indicating increase TF cooperativity in humans. By comparing network changes between different tissues, we discovered that in brain tissues, but not in the other tissues, the human networks always had the highest connectivity. To pinpoint molecular changes underlying species-specific phenotypes, we analyzed the sub-networks of TFs derived only from genes with species-specific expression changes in the PFC. These sub-networks differed significantly in structure and function between the human and chimpanzee. For example, the human-specific sub-network is enriched for TFs implicated in cognitive disorders and for genes involved in synaptic plasticity and cognitive functions. Our results suggest evolutionary changes in TF networks that might have shaped morphological and functional differences between primate brains, in particular in the human PFC.

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Human Evolution: Enhancing the Brain

Abstract: Humans have tripled their brain size since they split from the chimpanzee lineage. A new paper provides for the first time functional evidence that an enhancer contributed to this expansion by accelerating the cell cycle in neural progenitors.

Cited by 3 publications

References 21 publications

Human evolution: the non-coding revolution

Human evolution: the non-coding revolution

The DNA damage response molecule MCPH1 in brain development and beyond

Species-Specific Changes in a Primate Transcription Factor Network Provide Insights into the Molecular Evolution of the Primate Prefrontal Cortex

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