Where reductionism meets complexity: a call for growth in the study of non-growth

With the advent of metagenomics, we have unprecedented access to the genetic blueprint of the microbial world. Yet as metagenomic databases keep growing, our ability to interpret the information contained within them has not kept up. This conundrum arises from the fact that we cannot assign functions to the vast majority of their genes. As Jo Handelsman pointed out in a Crystal Ball piece two years ago, ‘the glory of the last 50 years of microbiology is founded, in large part, on genetic analysis’ (Handelsman, 2009). Amen. Yet as enticing as the prospect of environmental genetics or ‘metagenetics’ seems, how can we hope to interpret the unchartered world of environmental metagenomes when after more than a half-century of rigorous genetic and biochemical analyses, the functions of roughly a quarter of the genes in Escherichia coli – arguably the most well-studied organism on the planet – are still unknown (Karp et al., 2007)? Where have we gone wrong? Perhaps it is time to re-examine our assumptions about how to assign gene functions in light of lessons from the field