Evaluating intra- and inter-individual variation in the human placental transcriptome

• Type of Material: Article
• Authors: David A. Hughes, Max-Planck Institute for Evolutionary Anthropology; Martin Kircher, Max-Planck Institute for Evolutionary Anthropology; Zhisong He, CAS-MPG Partner Institute for Computational Biology; Song Guo, CAS-MPG Partner Institute for Computational Biology; Genevieve L. Fairbrother, Obstetrics and Gynecology of Atlanta; Carlos Moreno, Emory University; Philipp Khaitovich, CAS-MPG Partner Institute for Computational Biology; Mark Stoneking, Max-Planck Institute for Evolutionary Anthropology
• Language: English
• Date: 2015-03-19
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Hughes et al.; licensee BioMed Central.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13059-015-0627-z
• Title of Journal or Parent Work: Genome Biology
• ISSN: 1474-7596
• Volume: 16
• Issue: 1
• Start Page: 54
• End Page: 54
• Grant/Funding Information: The Max Planck Society and a grant for visiting young scientists from the Chinese Academy of Science (2009YB1-12) funded the project.
• Keywords: POLYMORPHISMS; GENOMIC REGIONS; FETAL-GROWTH; Genetics & Heredity; HUMAN-POPULATIONS; ALU-INSERTION; Biotechnology & Applied Microbiology; GENE-EXPRESSION PATTERNS; Science & Technology; Life Sciences & Biomedicine; EVOLUTIONARY; COUNT DATA; DIVERSITY; RNA-SEQ
• Research Categories: Anthropology, Medical and Forensic; Health Sciences, Obstetrics and Gynecology

Abstract

Background: Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. Results: We estimate that on average, 33.2%, 58.9%, and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals, and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they each account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling, and metabolism. Many biological traits demonstrate correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection, directional selection, or diversifying selection. Conclusions: We apportion placental gene expression variation into individual, population, and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.