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.

Download full-text

Full-text

Available from: Jeanna Strout, Feb 20, 2015
0 Followers
 · 
123 Views
  • Source
    06/2014; 2. DOI:10.3389/fevo.2014.00023
  • Source
    [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; DOI:10.1016/j.jprot.2013.12.019 · 3.93 Impact Factor
  • Source
    [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; DOI:10.1111/mec.12034 · 5.84 Impact Factor