The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence

Mekel-Bobrov, Nitzan; Posthuma, Daniëlle; Gilbert, Sandra L.; Lind, Penelope A.; Gosso, M.F.; Luciano, Michelle; Harris, Sarah E.; Bates, Timothy C.; Polderman, Tinca J. C.; Whalley, Lawrence J.; Fox, Helen; Starr, John M.; Evans, Patrick; Montgomery, Grant W.; Fernandes, Croydon; Heutink, Peter; Martin, Nicholas G.; Boomsma, Dorret I.; Deary, Ian J.; Wright, Margaret J.; Geus, Eco J. C. de; Lahn, Bruce T.

doi:10.1093/hmg/ddl487

Cited by 85 publications

(67 citation statements)

References 40 publications

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“…Furthermore, Yu et al 101 demonstrated that ASPM is not unusual compared with other anonymously selected regions in the genome, with respect to tests for selection based on population subdivision, haplotype structure and frequency spectrum, and argued that recent positive selection at this locus is unlikely. In addition, subsequent tests for an association between IQ and specific variants of ASPM and MCPH1 proved to be negative 102 .…”

Section: Box 2 Adaptation In Humansmentioning

confidence: 98%

Recent and ongoing selection in the human genome

et al. 2007

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The recent availability of genome-scale genotyping data has led to the identification of regions of the human genome that seem to have been targeted by selection. These findings have increased our understanding of the evolutionary forces that affect the human genome, have augmented our knowledge of gene function and promise to increase our understanding of the genetic basis of disease. However, inferences of selection are challenged by several confounding factors, especially the complex demographic history of human populations, and concordance between studies is variable. Although such studies will always be associated with some uncertainty, steps can be taken to minimize the effects of confounding factors and improve our interpretation of their findings.The past few years have seen an explosion of studies using molecular data to detect Darwinian natural selection [1][2][3][4][5][6] . With the recent availability of large-scale genotyping data, genome-wide scans for genes or genomic regions that have been targeted by selection have become feasible. These studies have greatly advanced our understanding of human evolution and molecular evolution in general, but they have also sparked considerable controversy.The interest in detecting selection is twofold. First, it stems from a natural curiosity about our evolutionary past and the basic mechanisms that govern molecular evolution. Much of the work in this field through the past four decades has focused on quantifying the relative importance of Darwinian selection and random genetic drift in determining levels of variability within species, as well as divergence between species (for example, REFS 7,8 ). However, as evidence accumulates for a strong role of selection, efforts are increasingly concentrating on identifying and characterizing particular instances of selection and adaptation at the molecular level. In humans, in particular, there has been a strong interest in identifying genes that have undergone recent selection relating to key human traits such as cognitive abilities 4,9,10 .Correspondence to R.N., rasmus@binf.ku.dk. DATABASES Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA second motivation for studying selection stems from the realization that inferences about selection can provide important functional information. For example, genes that are targeted by selection acting on segregating mutations are more likely to be associated with disease (for example, REF. 3 ). Even small fitness effects can, on an evolutionary timescale, leave a distinct pattern. Therefore, it might be possible to identify putative genetic disease factors by identifying regions of the human genome that currently are under selection 3,11 . In general, positions in the genome that are under selection must be of functional importance, otherwise selection could not be operating.The aim of this Review is to discuss some of the major findings regarding selection in humans, and explain...

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Section: Box 2 Adaptation In Humansmentioning

confidence: 98%

Recent and ongoing selection in the human genome

et al. 2007

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“…Indeed, two genes involved in brain development, MCPH1 and ASPM were both shown to continue to evolve adaptively in the human race. However, as yet none of the fast evolving genes could be linked directly to an adaptive phenotype, such as cognitive ability (e.g., Mekel-Bobrov et al 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Given the latter result, it is tempting to assume that ascertaining genes under recent positive selection would identify plausible candidate genes for complex traits (but see Mekel-Bobrov et al 2007). Here we present the results of a genome-wide search for genes that exhibit enhanced rate of protein evolution in primates.…”

Section: Introductionmentioning

confidence: 99%

A Functional Polymorphism under Positive Evolutionary Selection in ADRB2 is Associated with Human Intelligence with Opposite Effects in the Young and the Elderly

et al. 2008

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Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and chimpanzee. Positively selected genes among primates are generally presumed to determine phenotypic differences between humans and chimpanzee, such as the enhanced cognitive ability of our species. Amino acid substitutions segregating in humans at positively selected amino acid sites are expected to affect phenotypic differences among humans. Therefore we conducted an association study in two family based cohorts and one population based cohort between cognitive ability and the most likely candidate gene among the five that harbored more than one such polymorphism. The derived, human-specific allele of the beta-2 adrenergic receptor Arg16Gly polymorphism was found to be the increaser allele for performance IQ in the young, family based cohort but the decreaser allele for two different measures of cognition in the large Scottish cohort of unrelated individuals. The polymorphism is known to affect signaling activity and modulation of beta-2 adrenergic signaling has been shown to adjust memory consolidation, a trait related 123Behav Genet (2009) 39:15-23 DOI 10.1007 to cognition. The opposite effect of the polymorphism on cognition in the two age classes observed in the different cohorts resembles the effect of ADRB2 on hypertension, which also has been reported to be age dependent. This result illustrates the relevance of comparative genomics to detect genes that are involved in human behavior.

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“…A study of 1q21.1 CNVs and brain size found that deletions of the 1q21 region are associated with microcephaly, which is characterised by an abnormally small head, whereas duplications of this region are associated with macrocephaly, which is characterised by an abnormally large head (Brunetti-Pierri et al, 2008). Notably, the most striking trend in human evolution is the rapid increase in brain size over the past 3-4 million years, and the associated increase in complexity and cognitive capacity (Mekel-Bobrov et al, 2007). Because NBPF/DUF1220 is present in remarkably more copies in the human genome than in other primates (Vandepoele et al, 2005;Popesco et al, 2006), it was hypothesised that the NBPF/DUF1220 copy number is correlated with brain size (Dumas & Sikela, 2009).…”

Section: 3mentioning

confidence: 99%