Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens

  title={Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens},
  author={Nitzan Mekel-Bobrov and Sandra L. Gilbert and Patrick Evans and Eric J. Vallender and Jeffrey R. Anderson and Richard R. Hudson and Sarah A. Tishkoff and Bruce T. Lahn},
  pages={1720 - 1722}
The gene ASPM (abnormal spindle-like microcephaly associated) is a specific regulator of brain size, and its evolution in the lineage leading to Homo sapiens was driven by strong positive selection. Here, we show that one genetic variant of ASPM in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing… 
Comment on "Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens" and "Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans"
It is shown that models of human history that include both population growth and spatial structure can generate the observed patterns without selection.
Comment on "Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens"
When ASPM is compared empirically to a large number of other loci, its variation is not unusual and does not support selection.
Response to Comment on "Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens" and "Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans"
Computer simulations are presented to argue that the haplotype structure found at the microcephalin and ASPM genes can be better explained by demographic history rather than by selection.
The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.
The overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ, and highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.
Cytoskeletal genes regulating brain size.
MCPH , a disorder of neurogenic mitosis affecting foetal brain growth
One of the most notable trends in human evolution is the dramatic increase in brain size that has occurred in the great ape clade, culminating in humans, which is believed to have resulted in the authors' ability to perform higher cognitive functions.
Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals
Extensive evidence for positive selection having acted on the majority of microcephaly loci not just in primates but also across non-primate mammals is found, suggesting that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals.
Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees
The degree of coding variation at ASPM is characterized in a large sample of chimpanzees, and potential associations between genotype and various measures of brain morphology are examined, suggesting ASPM variation might play a role in shaping natural variation in brain structure in nonhuman primates.
ASPM and the Evolution of Cerebral Cortical Size in a Community of New World Monkeys
The results suggest that a multitude of interacting genes have driven the evolution of larger brains among primates, with different genes involved in this process in different encephalized lineages, or at least with evidence for positive selection not readily apparent for the same genes in all lineages.
Phylogenetic Analysis of ASPM, a Major Contributor Gene of Microcephaly
Bioinformatics analysis includes syntenic relationship of ASPM and its phylogenetic studies with reference to various selected orthologs revealed information about conservation of genes among different ortholog species and their evolutionary relationship.


Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans.
It is shown that the evolution of ASPM is significantly accelerated in great apes, especially along the ape lineages leading to humans, which is consistent with its putative role in the evolutionary enlargement of the human brain.
Genetic links between brain development and brain evolution
It is proposed that genes that regulate brain size during development, such as microcephaly genes, are chief contributors in driving the evolutionary enlargement of the human brain.
Evolution of the human ASPM gene, a major determinant of brain size.
Evidence is provided suggesting that human ASPM went through an episode of accelerated sequence evolution by positive Darwinian selection after the split of humans and chimpanzees but before the separation of modern non-Africans from Africans.
Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion
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,
ASPM is a major determinant of cerebral cortical size
It is shown that the most common cause of MCPH is homozygous mutation of ASPM, the human ortholog of the Drosophila melanogaster abnormal spindle gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts.
Signatures of natural selection in the human genome
Signs of natural selection left in the authors' genome can be used to identify genes that might underlie variation in disease resistance or drug metabolism, but these signatures are confounded by population history and by variation in local recombination rates.
Genetic Structure of the Ancestral Population of Modern Humans
This ancestral population was characterized by an effective size of about 10,000 as estimated from the nucleotide diversity; this size may describe the number of breeding individuals over a long time during the Middle Pleistocene or reflect a speciation bottleneck from an initially larger population at the end of this period.
Evolution of the brain and intelligence
Genetic Structure of Human Populations
General agreement of genetic and predefined populations suggests that self-reported ancestry can facilitate assessments of epidemiological risks but does not obviate the need to use genetic information in genetic association studies.