Abstract
BackgroundMany functional, structural and evolutionary features of human genes have been observed to correlate with expression breadth and/or gene age. Here, we systematically explore these correlations.ResultsGene age and expression breadth are strongly correlated, but contribute independently to the variation of functional, structural and evolutionary features, even when we take account of variation in mRNA expression level. Human genes without orthologs in distant species ('young' genes) tend to be tissue-specific in their expression. As computational inference of gene function often relies on the existence of homologs in other species, and experimental characterization is facilitated by broad and high expression, young, tissue-specific human genes are often the least characterized. At the same time, young genes are most likely to be medically relevant.ConclusionsOur results indicate that functional characterization of human genes is biased against young, tissue-specific genes that are mostly medically relevant. The biases should not be taken lightly because they may pose serious obstacles to our understanding of the molecular basis of human diseases. Future studies should thus be designed to specifically explore the properties of primate-specific genes.
Highlights
Many functional, structural and evolutionary features of human genes have been observed to correlate with expression breadth and/or gene age
We discuss systematic biases in functional studies that affect the process of knowledge acquisition for human diseaserelated genes. If it increases with expression breadth, it probably increases with age Using previously published phyletic age classifications [1] and expression breadth data [2,3], we first verified the substantial correlation between evolutionary age and expression breadth in human genes (Pearson’s correlation coefficient = 0.27, P < 10-15)
Consistent with our hypothesis of a later origin of proteins with more specific functions, we find that older genes are on average more broadly expressed, while young genes tend to be tissue-specific (Figure 1a), tissue-specificity is most pronounced for genes restricted to primates or mammals
Summary
Structural and evolutionary features of human genes have been observed to correlate with expression breadth and/or gene age. Younger genes perform more specialized functions, and are typically used and expressed in specific tissues and/or environments. This line of reasoning predicts a significant correlation between phyletic age and expression breadth. Many old genes are expected to be broadly useful (and broadly expressed), to come from basic functional groups (such as transcription/translation or metabolism), and to require distinct promoter architectures and optimized gene structures; they may evolve mostly under strong purifying selection
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