Defining genes: a computational framework

Abstract

The precise elucidation of the gene concept has become the subject of intense discussion in light of results from several, large high-throughput surveys of transcriptomes and proteomes. In previous work, we proposed an approach for constructing gene concepts that combines genomic heritability with elements of function. Here, we introduce a definition of the gene within a computational framework of cellular interactions. The definition seeks to satisfy the practical requirements imposed by annotation, capture logical aspects of regulation, and encompass the evolutionary property of homology.

Fig. 1

Functional objects a to e and relationships with their genomic footprints Γ(a) to Γ(e). A functional RNA molecule (e.g., a miRNA) with function Fct(a) is processed in two steps from an intronic sequence. Its image on the DNA is the genomic footprint Γ(a). The genomic footprint Γ(b) of the functional protein b is a discontinuous stretch of DNA corresponding to the coding sequence (CDS) including the start codon but excluding the stop codon. The mRNA includes UTRs that also map back to the DNA as well as parts without footprints on the DNA (the 5′-cap and the poly-A tail). The functional proteins c and d are obtained by cleavage of the (non-functional) precursor cd. The later is encoded by a trans-spliced mRNA. The footprint Γ(c) is distributed over two DNA molecules. The primary transcript e has an additional function Fct(e) that is independent of its role as precursor of the mRNA of cd. As a consequence, Γ(e) overlaps with both, Γ(c) and Γ(d). In all cases, the gene is the pair (Γ(x),x) composed of the genomic footprint Γ(x) and the resulting functional molecule x