Computational Identification of Novel Genes: Current and Future Perspectives

Abstract

While it has long been thought that all genomic novelties are derived from the existing material, many genes lacking homology to known genes were found in recent genome projects. Some of these novel genes were proposed to have evolved de novo, ie, out of noncoding sequences, whereas some have been shown to follow a duplication and divergence process. Their discovery called for an extension of the historical hypotheses about gene origination. Besides the theoretical breakthrough, increasing evidence accumulated that novel genes play important roles in evolutionary processes, including adaptation and speciation events. Different techniques are available to identify genes and classify them as novel. Their classification as novel is usually based on their similarity to known genes, or lack thereof, detected by comparative genomics or against databases. Computational approaches are further prime methods that can be based on existing models or leveraging biological evidences from experiments. Identification of novel genes remains however a challenging task. With the constant software and technologies updates, no gold standard, and no available benchmark, evaluation and characterization of genomic novelty is a vibrant field. In this review, the classical and state-of-the-art tools for gene prediction are introduced. The current methods for novel gene detection are presented; the methodological strategies and their limits are discussed along with perspective approaches for further studies.

Keywords: de novo genes; evolutionary genomics; gene detection; novel domains; novel genes.

Figure 1

Definition of novel genes based on phylogeny. Circles in the tree show gain of orphan (gray), novel (red), and de novo (green) genes. (A) Ancestral genome, ancestral genes are widely spread on the phylogenetic tree. (b) Ancestral acquisition of a gene, the orphan character is defined by its uniqueness among all currently known sequences. (C) Acquisition of a gene, the novel character is defined by hitherto absence on a considered phylogeny and is attributed by experts of the local taxonomy. (d) A genomic fragment gains transcriptional activity, constituting a de novo gene.