Comment on Papers by Evans
 et al
 . and Mekel-Bobrov
 et al
 . on Evidence for Positive Selection of
 MCPH1
 and
 ASPM

Timpson, Nicholas J.; Heron, Jon; Smith, George Davey; Enard, Wolfgang

doi:10.1126/science.1141705

Cited by 59 publications

(43 citation statements)

References 13 publications

(9 reference statements)

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“…Further, statistical inferences of evolutionary processes are prone to artefacts caused by other processes, such as changing population size 60,61 . Without experimental evidence of the functional or phenotypic impacts of mutations to corroborate such signatures, sequence-based statistical inferences remain thin and potentially misleading 32,62-64 .…”

Section: Why Evolutionary Biochemistry?mentioning

confidence: 99%

Evolutionary biochemistry: revealing the historical and physical causes of protein properties

2013

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The repertoire of proteins and nucleic acids in the living world is determined by evolution; their properties are determined by the laws of physics and chemistry. Explanations of these two kinds of causality — the purviews of evolutionary biology and biochemistry, respectively — are typically pursued in isolation, but many fundamental questions fall squarely at the interface of fields. Here we articulate the paradigm of evolutionary biochemistry, which aims to dissect the physical mechanisms and evolutionary processes by which biological molecules diversified and to reveal how their physical architecture facilitates and constrains their evolution. We show how an integration of evolution with biochemistry moves us towards a more complete understanding of why biological molecules have the properties that they do.

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Section: Why Evolutionary Biochemistry?mentioning

confidence: 99%

Evolutionary biochemistry: revealing the historical and physical causes of protein properties

2013

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“…A possible example of such a problem are two genes involved in the control of brain size, MCPH1 and ASPM (Evans et al 2006;Mekel-Bobrov et al 2005), which show an increased frequency of a derived haplotype outside Africa, interpreted to be the consequence of local positive selection for increased cognitive abilities in non-African populations. However, the link between the presence of the derived haplotype and a phenotypic trait could not be found (Dobson-Stone et al 2007;Mekel-Bobrov et al 2007;Timpson et al 2007;Woods et al 2006;Yu et al 2007). Moreover, we were able to show by performing spatially explicit simulations that similar geographic distributions of allele frequencies could be generated by allelic surfi ng of a neutral gene during the range expansion outside Africa ).…”

Section: Models Of Past Human Demographymentioning

confidence: 99%

Inferring Past Demography Using Spatially Explicit Population Genetic Models

Ray

Excoffier

2009

Human Biology

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Inferring the past demography of human populations has been classically approached through data from the archaeological record but more recently by the use of genetic data from contemporary samples. Building realistic demographic models at the continental scale is a necessary step toward the improvement of current genomic methods aimed at fi nding genes under selection. In light of recent advances in Bayesian statistical inference, we discuss here the importance of considering spatially explicit approaches for modeling population expansion and dispersal. Neutral processes, such as the surfi ng phenomenon, that occur at the front of a range expansion may indeed mimic selection, and they may have played a signifi cant role in spreading particular alleles over large geographic areas. Finally, we discuss a few important issues that require further investigation, notably the use of archaeological data to inform population genetic models, the simulation of range contraction and reexpansion, and the importance of long-distance dispersal.Keywords range expansion, human evolution, introgression, surfing phenomena, Bayesian inference, paleodemography, genetic diversity, population genetic models, SPLATCHE software. Cover Page FootnoteThis work was supported by the Swiss National Science Foundation through grant 3100A0-112072 awarded to L. Excoffier. We thank two anonymous reviewers for their comments on an earlier draft.This open access article is available in Human Biology: http://digitalcommons.wayne.edu/humbiol/vol81/iss2/3 Inferring Past Demography Using Spatially Explicit Population Genetic ModelsNicolas Ray 1,2 and Laurent Excoffier 1 Abstract Inferring the past demography of human populations has been classically approached through data from the archaeological record but more recently by the use of genetic data from contemporary samples. Building realistic demographic models at the continental scale is a necessary step toward the improvement of current genomic methods aimed at fi nding genes under selection. In light of recent advances in Bayesian statistical inference, we discuss here the importance of considering spatially explicit approaches for modeling population expansion and dispersal. Neutral processes, such as the surfi ng phenomenon, that occur at the front of a range expansion may indeed mimic selection, and they may have played a signifi cant role in spreading particular alleles over large geographic areas. Finally, we discuss a few important issues that require further investigation, notably the use of archaeological data to inform population genetic models, the simulation of range contraction and reexpansion, and the importance of long-distance dispersal.

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“…If the selected variants under question are still segregating in the human population, then many possibilities exist to test selective scenarios for example in large human cohorts (see e.g. [87] for such an approach). However, if the variants are fixed in humans, it is much more difficult to investigate the phenotypic consequences, although the case of a mouse model for studying the human-specific effects of FOXP2 might allow for careful optimism [68,88].…”

Section: Identifying Positively Selected Regions In the Human Genomementioning

confidence: 99%

Functional primate genomics—leveraging the medical potential

Enard

2012

J Mol Med

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Within biomedicine, comparative genomics is crucial for interpreting human genetic variants and building proper animal models. As our closest relatives, primates are of particular relevance in this frame work. Here, I review principles and concrete examples of this approach. Since one can expect that generating the necessary genomic DNA sequences will not be the major limiting factor in the near future, I argue that in analogy to human biomedicine, comprehensive phenotyping of different primates will be a crucial next step to tap the full potential of comparative genomics. Especially the possibility to generate pluripotent stem cells from primates should allow extending the comparative approach to many medically relevant questions.

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Comment on Papers by Evans et al . and Mekel-Bobrov et al . on Evidence for Positive Selection of MCPH1 and ASPM

Cited by 59 publications

References 13 publications

Evolutionary biochemistry: revealing the historical and physical causes of protein properties

Evolutionary biochemistry: revealing the historical and physical causes of protein properties

Inferring Past Demography Using Spatially Explicit Population Genetic Models

Functional primate genomics—leveraging the medical potential

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