Public Release:  Nurture over nature

Environmental factors weigh heavily in modulating gene expression in humans

North Carolina State University

Score one for the nurture side of the nature vs. nurture debate, as North Carolina State University geneticists have shown that environmental factors such as lifestyle and geography play a large role in whether certain genes are turned on or off.

By studying gene expression of white blood cells in 46 Moroccan Amazighs, or Berbers - including desert nomads, mountain agrarians and coastal urban dwellers - the NC State researchers and collaborators in Morocco and the United States showed that up to one-third of genes are differentially expressed due to where and how the Moroccan Amazighs live.

The research is published in the journal PLoS Genetics.

The NC State researchers, Youssef Idaghdour, an NC State graduate student in genetics and a Fulbright scholar, and Dr. Greg Gibson, formerly William Neal Reynolds Professor of Genetics at NC State and currently a faculty member at the University of Queensland in Australia, set out to study the impact of the transition from traditional to urbanized lifestyles on the human immune system. They used the latest tools for characterizing the sequence and expression of all 23,000 human genes to compare the three Moroccan Amazigh groups. These groups were chosen because they have a similar genetic makeup but lead distinct ways of life and occupy different geographic domains. Thus, differences in gene expression profiles between the three groups would likely be due to environmental and not genetic factors.

The team uncovered specific genes and pathways that are affected by lifestyle and geography. For example, they found respiratory genes were upregulated, or turned on, more frequently in the urban population than in the nomadic or agrarian populations.

This makes sense, Idaghdour says, as urban dwellers deal with greater amounts of pollution in the city and encounter more difficulties with diseases like asthma and bronchitis. So it stands to reason that certain respiratory genes in city dwellers go into overdrive while staying quiet in rural and nomadic populations, he adds.

The NC State researchers also examined every gene in each of the three populations and found very few genetic differences, positing that these limited differences were unlikely to explain the large gene expression differences.

Although Idaghdour initially hypothesized that environmental factors would play a role in gene expression, he didn't expect such large differences. About 30 percent of genes were differentially expressed between urban dwellers and mountain agrarians.

"The most important implication of this study is that people with the same genetic makeup can be in different environments and have different expression profiles," Idaghdour says. "The same gene can be expressed in the city but not in a rural place because of the environment. So you must look at the environment when studying associations between genes and disease."


Note to editors: An abstract of the paper follows.

"A Genomewide Gene Expression Signature of Environmental Geography in Leukocytes of Moroccan Amazighs"

Authors: Youssef Idaghdour and Greg Gibson, North Carolina State University; John D. Storey, Princeton University; and Sami J. Jadallah, HRH Prince Sultan International Foundation for Conservation and Development of Wildlife, Agadir, Morocco

Published: April 11, 2008, in PloS Genetics

Abstract: The different environments that humans experience are likely to impact physiology and disease susceptibility. In order to estimate the magnitude of the impact of environment on transcript abundance, we examined gene expression in peripheral blood leukocyte samples from 46 desert nomadic, mountain agrarian and coastal urban Moroccan Amazigh individuals. Despite great expression heterogeneity in humans, as much as one third of the leukocyte transcriptome was found to be associated with differences among regions. Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence. Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression. Genetic network analysis further implies that specific aspects of immune function are strongly affected by regional factors and may influence susceptibility to respiratory and inflammatory disease. Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans.

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