Discovering Functional Novelty in Metagenomes: Examples from Light-Mediated Processes

Abstract

The emerging coverage of diverse habitats by metagenomic shotgun data opens new avenues of discovering functional novelty using computational tools. Here, we apply three different concepts for predicting novel functions within light-mediated microbial pathways in five diverse environments. Using phylogenetic approaches, we discovered two novel deep-branching subfamilies of photolyases (involved in light-mediated repair) distributed abundantly in high-UV environments. Using neighborhood approaches, we were able to assign seven novel functional partners in luciferase synthesis, nitrogen metabolism, and quorum sensing to BLUF domain-containing proteins (involved in light sensing). Finally, by domain analysis, for RcaE proteins (involved in chromatic adaptation), we predict 16 novel domain architectures that indicate novel functionalities in habitats with little or no light. Quantification of protein abundance in the various environments supports our findings that bacteria utilize light for sensing, repair, and adaptation far more widely than previously thought. While the discoveries illustrate the opportunities in function discovery, we also discuss the immense conceptual and practical challenges that come along with this new type of data.One of the central questions in biology, starting from the time of Charles Darwin, has been the extent and distribution of biological diversity (68). The recent sequencing of several hundred bacterial and archaeal genomes and metagenomes, along with the discovery of large-scale lateral gene transfer (10) and recombination (25) in bacterial evolution, has not only renewed interest in the question of diversity but also confounded it. The sequencing projects reveal that contrary to previous estimates, it is microbes that account for the vast majority of diversity in phenotype and genotype on earth (44, 47). Underlying this dazzling diversity in species and habitat is molecular diversity. Indeed, we are just beginning to scratch the surface of this molecular diversity (50). Even though our understanding of how the living world functions at the molecular level is far from complete, the discovery of novel molecules has important applications to medicine, agriculture, industry, and environmental conservation and remediation.But how are we to discover functional novelty in the exponentially increasing amounts of sequenced genes and habitats (Fig.

Away from darkness: a review on the effects of solar radiation on heterotrophic bacterioplankton activity

“…Finally, the exploration of metagenomic data is unveiling a widespread distribution of photosensory proteins amongst aquatic bacteria (Singh et al, 2009). Various cellular functions such as pigment formation, DNA repair, stress responses, and the formation of biofilms or fruiting bodies are known to be mediated by light through different types of photoreceptors (Elías-Arnanz et al, 2011; van der Horst et al, 2007).…”

Genomics of the Proteorhodopsin-Containing Marine Flavobacterium Dokdonia sp. Strain MED134

“…Instead, these proteins most probably function as photolyases for DNA repair after UV damage, by using a photon of blue light to catalyze the reaction. This type of repair mechanism is frequently found in genomes of surface seawater prokaryotes (66). Finally, a BLUF domain that detects blue light is situated in a gene that is five genes away from prd and blh (Fig.…”

Novel function discovery through sequence and structural data mining

“…Functional associations may be inferred using a wide variety of techniques including detected protein enrichment in certain species or environments [52,63 ], genotype-phenotype correlations [82,83], networks analysis [84], and analysis of neighbouring gene or domain functions (genomic context or domain context) [85,86]. In addition, databases such as STRING provide predicted interactions based on gene fusions, gene neighbourhoods, coexpression, and gene co-occurrence [87] (Figure 1).…”