Abstract
Author SummaryThe level of protein produced by each gene corresponds approximately to the level of mRNA transcript produced by that gene: so high-abundance proteins, like those involved in protein synthesis, are represented by high-abundance transcripts, whereas low-abundance proteins, like those involved in signaling pathways, are represented by low-abundance transcripts. Furthermore, genetic variation can cause variation in transcript levels for the same gene between different individuals. These two observations have led to the assumption that inter-individual variation in transcript levels for any particular gene causes corresponding variation in protein levels. However, this need not be the case, because protein levels could be controlled not only by regulating transcript levels but also by regulating protein translation and stability. Because inter-individual variation in the levels of the transcript for any particular gene is typically less than 3-fold, rather than orders of magnitude, it is possible that the predominant cause of inter-individual variation in levels of any particular protein is transcription-independent regulation of protein levels. Here, we look in a genetically diverse population of 95 yeast strains at the genetic variation that leads in turn to variation in levels of 354 proteins that function within co-regulated networks. We find that the between-strain variation predominantly reflects transcription-independent mechanisms. If this result is typical of the proteome as a whole, it suggests that protein levels in genetically diverse populations cannot be accurately inferred from levels of their underlying transcripts.
Highlights
Genetic variation leads to networks of co-regulated transcripts
The level of protein produced by each gene corresponds approximately to the level of mRNA transcript produced by that gene: so high-abundance proteins, like those involved in protein synthesis, are represented by highabundance transcripts, whereas low-abundance proteins, like those involved in signaling pathways, are represented by low-abundance transcripts
Genetic variation can cause variation in transcript levels for the same gene between different individuals. These two observations have led to the assumption that inter-individual variation in transcript levels for any particular gene causes corresponding variation in protein levels
Summary
Genetic variation leads to networks of co-regulated transcripts. The implications of these network structures have been discussed extensively, generally with the assumption that such transcriptional networks give rise to corresponding protein networks [1,2,3,4,5,6]. The demonstration in multiple studies that the correlation between transcript and protein levels for different genes within a single individual is high does not imply that differences in abundance of the same transcripts between different individuals must cause corresponding variation in protein abundance [8,9]. A correlation between transcript and protein networks does not prove a causal relationship between the two
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