NEW YORK (GenomeWeb News) – New research is delving into the nature of environmental and genetic influences on gene expression using microarray technology and yeast genetics.
A research duo based at Princeton and Washington Universities used microarray analysis to compare the gene expression of yeast cells from different genetic backgrounds grown in different carbon sources. In the process, they determined that both strain and environment-related changes in gene expression are relatively common. The research, which appeared online today in the journal PLoS Biology, also provides insights into the types of genetic patterns that are most often associated with each.
“We have investigated gene-environment interaction on a genomic level, characterizing its role in over 4,000 traits at once by investigating natural variation in yeast gene expression,” the authors wrote.
The influence of the environment on gene expression is compelling given that gene-environment interactions seem to play a part in some human diseases such as heart disease and cancer.
For this study, Erin Smith, a genomics researcher and evolutionary biologist at Princeton University, and Leonid Kruglyak, a molecular and cellular biologist at the University of Washington, focused on yeast cells, comparing strains that originated in the lab with strains isolated from vineyards — and strains generated by crossing the two — grown using different carbon sources.
Because yeast metabolism varies depending on the carbon source, yeast cells produce drastically different transcripts depending on how they’re grown. Yeast ferment glucose to make ethanol, for example. But when they’re actually grown in ethanol, they usually do aerobic respiration.
To compare different yeast genetic backgrounds, the researchers crossed two yeast strains — called BY and RM — and studied 109 segregant strains from this cross. They then grew each strain in glucose or ethanol and hybridized their RNA to Agilent 11K yeast arrays containing more than 6,000 transcripts. The researchers also did similar experiments with parental strains, which were compared with one another and used as references in for segregant experiments.
Specifically, they focused on 4,342 parental transcripts and 4,482 segregant transcripts for their analysis. For each strain and condition, Smith and Kruglyak tested six independent cultures.
The results suggest that both strain and environmental differences have profound effects on gene expression. In the parental strains, for instance, 47 percent of the transcripts tested varied based on interactions between a particular strain and the conditions under which they were tested. Even more — 69 percent and 79 percent, respectively — varied by strain and environmental conditions.
The team also did linkage analyses as part of their genetic appraisal. In the segregant strains, for example, they found nearly 4,000 linkages in glucose and almost 3,500 linkages in ethanol. To find the loci with gene-environment interactions, they did linkage analysis on the differences detected between carbon sources calculated from the 4,482 transcripts tested. Nearly 1,400 showed gene-environment interactions in at least one locus.
They also determined whether such linkages were local or distant and the relative environmental or strain-related effects at each. They noted that roughly a quarter of linkages were local. And the distant linkages, which were more often linked to the environment, tended to cluster in peaks at certain parts of the genome.
“[L]ocal linkages are overall less dependant on the environment, and when they do show gene-environment interaction, their effects are less likely to be restricted to a specific condition,” the authors wrote.
Not surprisingly, growing cells in different carbon sources altered the expression of genes related to energy metabolism and growth. By characterizing a region associated with growth, the team also started to unravel specific genes that act to turn the expression of other genes up or down. For instance, they concluded that a gene called IRA2, which codes for a protein that inhibits glucose response proteins in the Ras/PKA pathway, can dictate the expression of many growth-related transcripts.
“Our results provide a broad overview of the genetic architecture of gene-environment interactions, as well as a detailed molecular example, and lead to key insights into how the effects of different classes of regulatory variants are modulated by the environment,” Smith and Kruglyak wrote.