Environment vs Inheritance – Air Pollutants Account for More Variation in Gene Expression than Ancestry, Transcriptome Analysis Reveals

Overview

Researchers at the Ontario Institute for Cancer Research use RNA-sequence methods to generate transcription profiles of over 1000 French Canadians and find correlations between a number of environmental factors, chiefly air composition.

Advancements in molecular sequencing allow for high-throughput analysis of genomic information[1]. As a result, clinics around the world are using sequence methods, coupled with their clinical history, to generate profiles and find links between genetics and illness[2]. In this study, researchers compare environmental vs ancestral associations with transcpritonal profiles.

Transcriptional Profiling

A person’s transcriptome is the sum total of the RNA that their cells produce. It is, loosely, a way of quantifying your bodies production (or transcription) of an particular gene. Transciptional activity is something that can be turned on or off, like a switch, in response to a number of factors. Commonly, these factors are grouped into two categories, genetic and environmental. Genetic, or ancestral, factors boil down to a person’s DNA. Simply put, some people may naturally have higher expression of a gene because it is a trait they inherited. It is, outside of mutagenesis, not malleable, but still contributes to the expression profile. Environmental factors are any number of external stimuli- chemical, radiologic, audiologic, etc.- that affects the bodies rate in which it produces, or transcribes, a particular gene. A key aspect of this study is to determine whether environmental factors contribute more to a person’s transcriptional profile than their ancestry.

SO2Transcriptome

Environmental vs Ancestral Effects on Transcriptome

The study sampled individuals from 3 locations with varying environmental dynamics- Montreal, Quebec City, and Saguenay- and determined ancestry via genotyping of ca. 2 million SNP’s. Essentially, individuals from each locale were be cohorted by regional ancestry. I.E.

Montreal: Native, Quebec City migrant, Saguenay migrant

Quebec City: Native, Montreal migrant, Saguenay migrant

Saguenay- Native, Montreal migrant, Quebec City migrant

Principal component analysis on the transcriptomes revealed that a person’s ancestry had marginal contributions to their profile in comparison to locality. For example, 2 people with Montreal ancestry living in different cities would differ more in their profiles than 2 people – 1 with Quebec City ancestry and 1 with Montreal ancestry- both living in Montreal. Overall, 170 differentially expressed genes were identified between locations.

figure2
Figure 2 from original study showing variation in expression is greater between environmental cohorts than ancestral ones.

Sulfur Dioxide is a Chief Contributor in Transcriptome Variation

The 3 locations selected have particular environmental conditions, due to a number of factors such as population density and urbanization. This study considered several factors ranging from number of parks, to food availability, to atmospheric composition. Cointertia analysis on randomly separated cohorts of these environmental exposures pinpointed sulfur dioxide as a chief contributor of transcriptome variation.

Emitted as a byproduct from the combustion of fossil fuels, SO2 levels are higher in industrialized zones, like Montreal, in this case. Health effects include respiratory problems and lung damage[3], but what does this look like at the molecular level?

Further experimentation involving direct exposure of blood samples to controlled levels of SO2 pinpointed associated expression levels. Within the 170 differentially expressed genes, a number of affected pathways were identified. Chiefly, those involved with the transport of oxygen or white blood cells; including: hemoglobin complex, chemokine-mediated signaling pathway, leukocyte chemotaxis, et.al.

Takeaways

The key takeaway from this study, I think, is not the correlation between pollutants and gene expression. Not that these factors are not important within a public health context, just that this has been established before and is well known. The principal finding for me is that environmental factors account for more transcriptome variation than hereditary ones. Within the context the nature vs nurture paradigm, nurture gets awarded a point, here.

References

  1. Reuter JA, Spacek D, Snyder MP. High-Throughput Sequencing Technologies. Molecular cell. 2015;58(4):586-597. doi:10.1016/j.molcel.2015.05.004.
  2. Casamassimi A, Federico A, Rienzo M, Esposito S, Ciccodicola A. Transcriptome Profiling in Human Diseases: New Advances and Perspectives. International Journal of Molecular Sciences. 2017;18(8):1652. doi:10.3390/ijms18081652.
  3. Kampa M, Castanas E. Human Health Effects of Air pollution. Environmental Pollution. Volume 151, Issue 2, January 2008, Pages 362-367. doi:https://doi.org/10.1016/j.envpol.2007.06.012

Original Study

Favé M-J, et.al. Gene-by-environment interactions in urban populations modulate risk phenotypes. Nature Communications 9, Article number: 827 (2018). doi:10.1038/s41467-018-03202-2

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