title: The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.
abstract: Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.
authors.affiliation: Department of Human Genetics, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Nitzan
authors.initials: N
authors.lastname: Mekel-Bobrov
authors.forename: Danielle
authors.initials: D
authors.lastname: Posthuma
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Gilbert
authors.forename: Penelope
authors.initials: P
authors.lastname: Lind
authors.forename: M Florencia
authors.initials: MF
authors.lastname: Gosso
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Bates
authors.forename: Tinca J C
authors.initials: TJ
authors.lastname: Polderman
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Whalley
authors.forename: Helen
authors.initials: H
authors.lastname: Fox
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Evans
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Croydon
authors.initials: C
authors.lastname: Fernandes
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Lahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D005075:Biological Evolution; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002648:Child; D003598:Cytoskeletal Proteins; D019143:Evolution, Molecular; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics; D008967:Molecular Biology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide
chemical_list: C467202:ASPM protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins