Considerations for the use of transcriptomics in identifying the 'genes that matter' for environmental adaptation.

Transcriptomics has emerged as a powerful approach for exploring physiological responses to the environment. However, like any other experimental approach, transcriptomics has its limitations. Transcriptomics has been criticized as an inappropriate method to identify genes with large impacts on adaptive responses to the environment because: (1) genes with large impacts on fitness are rare; (2) a large change in gene expression does not necessarily equate to a large effect on fitness; and (3) protein activity is most relevant to fitness, and mRNA abundance is an unreliable indicator of protein activity. In this review, these criticisms are re-evaluated in the context of recent systems-level experiments that provide new insight into the relationship between gene expression and fitness during environmental stress. In general, these criticisms remain valid today, and indicate that exclusively using transcriptomics to screen for genes that underlie environmental adaptation will overlook constitutively expressed regulatory genes that play major roles in setting tolerance limits. Standard practices in transcriptomic data analysis pipelines may also be limiting insight by prioritizing highly differentially expressed and conserved genes over those genes that undergo moderate fold-changes and cannot be annotated. While these data certainly do not undermine the continued and widespread use of transcriptomics within environmental physiology, they do highlight the types of research questions for which transcriptomics is best suited and the need for more gene functional analyses. Such information is pertinent at a time when transcriptomics has become increasingly tractable and many researchers may be contemplating integrating transcriptomics into their research programs.