Article

Gene-Expression Variation Within and Among Human Populations

Department of Biostatistics, University of Washington, Seattle, WA 98195-7730, USA.
The American Journal of Human Genetics (Impact Factor: 10.99). 04/2007; 80(3):502-9. DOI: 10.1086/512017
Source: PubMed

ABSTRACT Understanding patterns of gene-expression variation within and among human populations will provide important insights into the molecular basis of phenotypic diversity and the interpretation of patterns of expression variation in disease. However, little is known about how gene-expression variation is apportioned within and among human populations. Here, we characterize patterns of natural gene-expression variation in 16 individuals of European and African ancestry. We find extensive variation in gene-expression levels and estimate that approximately 83% of genes are differentially expressed among individuals and that approximately 17% of genes are differentially expressed among populations. By decomposing total gene-expression variation into within- versus among-population components, we find that most expression variation is due to variation among individuals rather than among populations, which parallels observations of extant patterns of human genetic variation. Finally, we performed allele-specific quantitative polymerase chain reaction to demonstrate that cis-regulatory variation in the lymphocyte adaptor protein (SH2B adapter protein 3) contributes to differential expression between European and African samples. These results provide the first insight into how human population structure manifests itself in gene-expression levels and will help guide the search for regulatory quantitative trait loci.

0 Followers
 · 
128 Views
  • Source
    • "Variations within and among populations are critical for understanding species-range structure and dynamics (Storey et al., 2007; Bertocci et al., 2011; Guo, 2012). Both population size and density are main elements reflecting population structure and dynamics. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The species’ range limits and associated central-marginal (C-M; i.e., from species range center to margin) population dynamics continue to draw increasing attention because of their importance for current emerging issues such as biotic invasions and epidemic diseases under global change. Previous studies have mainly focused on species borders and C-M process in natural settings for native species. More recently, growing efforts are devoted to examine the C-M patterns and process for invasive species partly due to their relatively short history, highly dynamic populations, and management implications. Here I examine recent findings and information gaps related to (1) the C-M population dynamics linked to species invasions, and (2) the possible effects of climate change and land use on the C-M patterns and processes. Unlike most native species that are relatively stable (some even having contracting populations or ranges), many invasive species are still spreading fast and form new distribution or abundance centers. Because of the strong nonlinearity of population demographic or vital rates (i.e. birth, death, immigration and emigration) across the C-M gradients and the increased complexity of species ranges due to habitat fragmentation, multiple introductions, range-wide C-M comparisons and simulation involving multiple vital rates are needed in the future.
    06/2014; 2. DOI:10.3389/fevo.2014.00023
  • Source
    • "The vast majority of such studies compare group means in expression levels, while much less attention has been given to the occurrence and potential significance of within-population gene expression variation. However, large inter-individual differences in gene expression variation within populations have in fact been observed in organisms as diverse as teleost fish [18] [19], Drosophila melanogaster [20], and humans [21]. Such variation can drive differences in the physiological performance between individuals [19] [22], affect disease susceptibility [23], and therefore may be of functional and biological importance. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Variation in gene expression is an important component of the phenotypic differences observed in nature. Gene expression variance across biological groups and environmental conditions has been studied extensively and has revealed specific genes and molecular mechanisms of interest. However, little is known regarding the importance of within-population gene expression variation to environmental adaptation. To address this issue, we quantified the proteomes of individuals of European whitefish (Coregonus lavaretus) from populations that have previously been shown to have adapted during early development to freshwater and brackishwater salinity environments. Using MS-based label-free proteomics, we studied 955 proteins in eight hatch-stage fish embryos from each population to both freshwater and brackishwater salinity conditions. By comparing the levels of within-population protein expression variance over individuals and per protein between populations, we found that fish embryos from the population less affected by salinity had also markedly higher levels of expression variance. Gene Ontologies and molecular pathways associated with osmoregulation showed the most significant difference of within-population proteome variance between populations. Several new candidate genes for salinity adaptation were identified, emphasising the added value of combining assessments of within-population gene expression variation with standard gene expression analysis practices for better understanding the mechanisms of environmental adaptation. We demonstrate the benefits of studying within-population gene expression variance together with more typical methods of gene expression profiling. Proteome variance differences within European whitefish populations originating from different salinity environments allowed us to identify several new candidate genes for salinity adaptation in teleost fish and generate many further hypotheses to be tested. This article is part of a Special Issue entitled: Proteomics of non-model organisms.
    Journal of proteomics 01/2014; 105. DOI:10.1016/j.jprot.2013.12.019 · 3.93 Impact Factor
  • Source
    • "Recent advances in DNA sequencing technology allow the rapid acquisition of vast, genomic-scale resources and permit the collection of transcriptomic data for ecological as well as evolutionary model species (Stapley et al. 2010). Before sequence-based transcriptomics, it was microarrays and qPCR techniques based on a priori sequence information that revealed the importance of gene expression differentiation in the diversification of natural populations (Oleksiak et al. 2002; Storey et al. 2007; Pavey et al. 2010), particularly in the phenotypic divergence of teleost populations (e.g. Derome et al. 2006; Kobayashi et al. 2006; St-Cyr et al. 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The study of parallel evolution facilitates the discovery of common rules of diversification. Here, we examine the repeated evolution of thick lips in Midas cichlid fishes (the Amphilophus citrinellus species complex)-from two Great Lakes and two crater lakes in Nicaragua-to assess whether similar changes in ecology, phenotypic trophic traits and gene expression accompany parallel trait evolution. Using next-generation sequencing technology, we characterize transcriptome-wide differential gene expression in the lips of wild-caught sympatric thick- and thin-lipped cichlids from all four instances of repeated thick-lip evolution. Six genes (apolipoprotein D, myelin-associated glycoprotein precursor, four-and-a-half LIM domain protein 2, calpain-9, GTPase IMAP family member 8-like and one hypothetical protein) are significantly underexpressed in the thick-lipped morph across all four lakes. However, other aspects of lips' gene expression in sympatric morphs differ in a lake-specific pattern, including the magnitude of differentially expressed genes (97-510). Generally, fewer genes are differentially expressed among morphs in the younger crater lakes than in those from the older Great Lakes. Body shape, lower pharyngeal jaw size and shape, and stable isotopes (δ(13) C and δ(15) N) differ between all sympatric morphs, with the greatest differentiation in the Great Lake Nicaragua. Some ecological traits evolve in parallel (those related to foraging ecology; e.g. lip size, body and head shape) but others, somewhat surprisingly, do not (those related to diet and food processing; e.g. jaw size and shape, stable isotopes). Taken together, this case of parallelism among thick- and thin-lipped cichlids shows a mosaic pattern of parallel and nonparallel evolution.
    Molecular Ecology 10/2012; 22. DOI:10.1111/mec.12034 · 6.49 Impact Factor
Show more