scholarly journals Proteolytic Activation of Human-specific Olduvai Domains by the Furin Protease

2021 ◽  
Author(s):  
Ashley Pacheco ◽  
Aaron Issaian ◽  
Jonathan Davis ◽  
Nathan Anderson ◽  
Travis Nemkov ◽  
...  
Keyword(s):  
Human Brain ◽  
Copy Number ◽  
Brain Size ◽  
Active Agent ◽  
Brain Evolution ◽  
Variable Number ◽  
Coding Region ◽  
Proteolytic Activation ◽  
Highly Correlated ◽  
Human Specific

Olduvai protein domains (formerly DUF1220) show the greatest human-specific increase in copy number of any coding region in the genome and are highly correlated with human brain evolution and cognitive disease. The majority of human copies are found within four NBPF genes organized in a variable number of a tandemly arranged three-domain blocks called Olduvai triplets. Here we show that these human-specific Olduvai domains are posttranslationally processed by the furin protease, with a cleavage site occurring once at each triplet. These findings suggest that all expanded human-specific NBPF genes encode proproteins consisting of many independent Olduvai triplet proteins which are activated by furin processing. The exceptional correlation of Olduvai copy number and brain size taken together with our new furin data, indicates the ultimate target of selection was a rapid increase in dosage of autonomously functioning Olduvai triplet proteins, and that these proteins are the primary active agent underlying Olduvai's role in human brain expansion.

scholarly journals Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution

2018 ◽  
Author(s):  
Alex A Pollen ◽  
Aparna Bhaduri ◽  
Madeline G Andrews ◽  
Tomasz J Nowakowski ◽  
Olivia S Meyerson ◽  
...  
Keyword(s):  
Human Brain ◽  
Regulatory Networks ◽  
Radial Glia ◽  
Brain Size ◽  
Metabolic Stress ◽  
Brain Evolution ◽  
Cell Types ◽  
Segmental Duplications ◽  
Systematic Analysis ◽  
Human Specific

Direct comparisons of human and non-human primate brain tissue have the potential to reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is largely 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. First, we systematically evaluated the fidelity of organoid models to primary human and macaque cortex, finding organoid models preserve gene regulatory networks related to cell types and developmental processes but exhibit increased metabolic stress. Second, we identified 261 genes differentially expressed in human compared to chimpanzee organoids and macaque cortex. Many of these genes overlap with human-specific segmental duplications and a subset suggest increased PI3K/AKT/mTOR activation in human outer radial glia. Together, our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.

scholarly journals Emerging Roles of Long Non-Coding RNAs as Drivers of Brain Evolution

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1399 ◽  
Author(s):  
Geraldine Zimmer-Bensch
Keyword(s):  
Human Brain ◽  
Cognitive Abilities ◽  
Brain Size ◽  
Expression Patterns ◽  
Brain Evolution ◽  
Relative Volume ◽  
Structural Reorganization ◽  
Protein Coding ◽  
Human Brain Evolution ◽  
Transcriptional Regulatory

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain with precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of lncRNAs have newly appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. lncRNAs are increasingly reported to be involved in neurodevelopmental processes suggested to underlie human brain evolution, including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

scholarly journals Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels

2020 ◽  
Vol 37 (9) ◽  
pp. 2531-2548
Author(s):  
Gerrald A Lodewijk ◽  
Diana P Fernandes ◽  
Iraklis Vretzakis ◽  
Jeanne E Savage ◽  
Frank M J Jacobs
Keyword(s):  
Human Brain ◽  
Brain Size ◽  
Modern Human ◽  
Copy Number Variations ◽  
Optimal Dosage ◽  
Protein Coding ◽  
Protein Levels ◽  
Human Genomes ◽  
Coding Variants ◽  
Human Specific

Abstract Ever since the availability of genomes from Neanderthals, Denisovans, and ancient humans, the field of evolutionary genomics has been searching for protein-coding variants that may hold clues to how our species evolved over the last ∼600,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive toward low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population.

Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution

2016 ◽  
Vol 136 (2) ◽  
pp. 193-204 ◽  
Author(s):  
Lei Shi ◽  
Enzhi Hu ◽  
Zhenbo Wang ◽  
Jiewei Liu ◽  
Jin Li ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Size ◽  
Brain Evolution ◽  
Human Brain Evolution ◽  
The Brain ◽  
Insight Into ◽  
Selection Of

scholarly journals Emerging Roles of Long Non-Coding RNAs as Drivers of Brain Evolution

2019 ◽  
Author(s):  
Geraldine Zimmer-Bensch
Keyword(s):  
Human Brain ◽  
Cognitive Abilities ◽  
Brain Size ◽  
Expression Patterns ◽  
Brain Evolution ◽  
Relative Volume ◽  
Structural Reorganization ◽  
Protein Coding ◽  
Human Brain Evolution ◽  
Transcriptional Regulatory

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

scholarly journals The impact of locomotion on the brain evolution of squirrels and close relatives

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ornella C. Bertrand ◽  
Hans P. Püschel ◽  
Julia A. Schwab ◽  
Mary T. Silcox ◽  
Stephen L. Brusatte
Keyword(s):  
Body Mass ◽  
Brain Size ◽  
Brain Evolution ◽  
Olfactory Bulbs ◽  
Component Size ◽  
Highly Correlated ◽  
Close Relatives ◽  
The Impact ◽  
The Brain ◽  
Opposing Effect

AbstractHow do brain size and proportions relate to ecology and evolutionary history? Here, we use virtual endocasts from 38 extinct and extant rodent species spanning 50+ million years of evolution to assess the impact of locomotion, body mass, and phylogeny on the size of the brain, olfactory bulbs, petrosal lobules, and neocortex. We find that body mass and phylogeny are highly correlated with relative brain and brain component size, and that locomotion strongly influences brain, petrosal lobule, and neocortical sizes. Notably, species living in trees have greater relative overall brain, petrosal lobule, and neocortical sizes compared to other locomotor categories, especially fossorial taxa. Across millions of years of Eocene-Recent environmental change, arboreality played a major role in the early evolution of squirrels and closely related aplodontiids, promoting the expansion of the neocortex and petrosal lobules. Fossoriality in aplodontiids had an opposing effect by reducing the need for large brains.

scholarly journals Accelerated evolution of oligodendrocytes in human brain

2019 ◽  
Author(s):  
Stefano Berto ◽  
Isabel Mendizabal ◽  
Noriyoshi Usui ◽  
Kazuya Toriumi ◽  
Paramita Chatterjee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Rhesus Macaques ◽  
Brain Evolution ◽  
Cell Types ◽  
Specific Expression ◽  
Accelerated Evolution ◽  
Human Brain Evolution ◽  
Cell Type Specific Expression ◽  
Human Specific

SUMMARYRecent 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 similar or 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 neurons and oligodendrocytes and show that both cell-types exhibit human-specific upregulation. Moreover, oligodendrocytes have undergone accelerated gene expression evolution in the human lineage compared to neurons. 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.

scholarly journals Genetic Mechanisms Underlying the Evolution of Connectivity in the Human Cortex

2022 ◽  
Vol 15 ◽  
Author(s):  
Ewoud R. E. Schmidt ◽  
Franck Polleux
Keyword(s):  
Human Brain ◽  
Molecular Mechanisms ◽  
Brain Size ◽  
Cognitive Capacity ◽  
Genetic Modifiers ◽  
Physiological Properties ◽  
Human Neurons ◽  
Genetic Mechanisms ◽  
And Function ◽  
Human Specific

One of the most salient features defining modern humans is our remarkable cognitive capacity, which is unrivaled by any other species. Although we still lack a complete understanding of how the human brain gives rise to these unique abilities, the past several decades have witnessed significant progress in uncovering some of the genetic, cellular, and molecular mechanisms shaping the development and function of the human brain. These features include an expansion of brain size and in particular cortical expansion, distinct physiological properties of human neurons, and modified synaptic development. Together they specify the human brain as a large primate brain with a unique underlying neuronal circuit architecture. Here, we review some of the known human-specific features of neuronal connectivity, and we outline how novel insights into the human genome led to the identification of human-specific genetic modifiers that played a role in the evolution of human brain development and function. Novel experimental paradigms are starting to provide a framework for understanding how the emergence of these human-specific genomic innovations shaped the structure and function of neuronal circuits in the human brain.

Diet and Brain Evolution: Nutritional Implications of Large Human Brain Size

2011 ◽  
pp. 3-15
Author(s):  
William R. Leonard ◽  
J. Josh Snodgrass ◽  
Marcia L. Robertson
Keyword(s):  
Human Brain ◽  
Brain Size ◽  
Brain Evolution

Putting humans in their proper place

2006 ◽  
Vol 29 (1) ◽  
pp. 15-16 ◽  
Author(s):  
R. I. M. Dunbar
Keyword(s):  
Human Brain ◽  
Brain Size ◽  
Brain Evolution ◽  
Developmental Constraints ◽  
Proper Place ◽  
Human Brain Evolution ◽  
Machiavellian Intelligence ◽  
Initial Jump

Striedter's account of human brain evolution fails on two key counts. First, he confuses developmental constraints with selection explanations in the initial jump in hominid brain size around two MYA. Second, he misunderstands the Machiavellian Intelligence explanation.

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