ArticlePLoS biology2004
Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.
Article in PLoS biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 197 citations in OpenAlex.
- Reduced Adult Neurogenesis in Humans Results From a Tradeoff Rather Than Direct Negative Selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- A new cancer/testis long noncoding RNA, the OTP-AS1 RNA.Scientific reports · 2024Article
- Cocaine diminishes functional network robustness and destabilizes the energy landscape of neuronal activity in the medial prefrontal cortex.PNAS nexus · 2024Article
- Review
- Article
- Comparative landscape of genetic dependencies in human and chimpanzee stem cells.bioRxiv : the preprint server for biology · 2023Article
- Review
- Equivocal evidence for a link between megalencephaly-related genes and primate brain size evolution.Scientific reports · 2022Article
- Highly Selective, CRISPR/Cas9-Mediated Isolation of Genes and Genomic Loci from Complex Genomes by TAR Cloning in Yeast.Current protocols · 2021Article
- Oncogenic role of abnormal spindle‑like microcephaly‑associated protein in lung adenocarcinoma.International journal of oncology · 2021Article
- A Likelihood Approach for Uncovering Selective Sweep Signatures from Haplotype Data.Molecular biology and evolution · 2020Article
- The journey of Zika to the developing brain.Molecular biology reports · 2020Review
- TAR Cloning: Perspectives for Functional Genomics, Biomedicine, and Biotechnology.Molecular therapy. Methods & clinical development · 2019Review
- Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees.Genes, brain, and behavior · 2019Article
- Overexpression of the ASPM gene is associated with aggressiveness and poor outcome in bladder cancer.Oncology letters · 2019Article
- Untangling Cortical Complexity During Development.Journal of experimental neuroscience · 2018Review
- Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.Human genetics · 2017Article
- Whole exome sequencing identifies a novel homozygous frameshift mutation in the ASPM gene, which causes microcephaly 5, primary, autosomal recessive.F1000Research · 2017Article
- Transformation-associated recombination (TAR) cloning for genomics studies and synthetic biology.Chromosoma · 2016Review
- The cytoskeletal arrangements necessary to neurogenesis.Oncotarget · 2016Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.
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Registered trials
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.