small ORFs: A new class of essential genes for development

Abstract

Genes that contain small open reading frames (smORFs) constitute a new group of eukaryotic genes and are expected to represent 5% of the Drosophila melanogaster transcribed genes. In this review we provide a historical perspective of their recent discovery, describe their general mechanism and discuss the importance of smORFs for future genomic and transcriptomic studies. Finally, we discuss the biological role of the most studied smORF so far, the Mlpt/Pri/Tal gene in arthropods. The pleiotropic action of Mlpt/Pri/Tal in D. melanogaster suggests a complex evolutionary scenario that can be used to understand the origins, evolution and integration of smORFs into complex gene regulatory networks.

Keywords: Drosophila; Tribolium; mlpt; pri; tarsal-less.

Figure 1. Scheme of the general method for the identification of smORFs in different related species. Based on primary data and schemes from Kessler et al. (2003)and Ladoukakis et al.(2011). smORF prediction is based on detection and filtering. The filtering process is important to reduce the false positive rate and increase the efficacy of functional smORFs estimation.

Figure 2. Schematic drawings of the generation of biologically active short peptides. A similar scheme was published by Hashimoto et al. (2008). (A) Hormones and neuropeptides are generated via a large mRNA precursor (blue) in the nucleus, then translated by ribosomes (green) from a single initiation codon and finally processed in the ER and Golgi into small peptides, which are subsequently secreted by vesicles to act far from the production site. (B) Polycistronic smORFs (red) can be translated by several ribosomes (green) along a single mRNA, followed by cell secretion. Peptides from smORFs can also act far from the releasing cell.

Figure 3. Evolution and functional role of Mlpt/Tal/Pri in arthropods. Several arthropods display an ortholog of Mlpt/Tal/Pri (original alignments and phylogenetic trees from Galindo et al., 2007 and Savard et al., 2006). In the short-germ embryo of the beetle Tribolium castaneum, mlpt was shown to be expressed in the legs and trachea, where it acts as a gap gene during embryogenesis (Savard et al., 2006). In the long-germ embryo of the fly Drosophila melanogaster, Mlpt/Tal/Pri was shown to be involved in several processes, which are displayed in red (Chanut-Delalande et al., 2014; Galindo et al., 2007; Kondo et al., 2007, 2010; Pueyo and Couso, 2008, 2011). Notch, Svb and EcR are the known regulators of Mlpt/Tal/Pri (Chanut-Delalande et al., 2014). Three unknown aspects of the evolution of Mlpt/Tal/Pri are highlighted in blue. These include the origin of the gene in arthropods, its ancestral function, and the loss of gap gene function after the split between the common ancestor of Coleoptera and Diptera. It is also possible that the gap gene function of Mlpt/Tal/Pri was independently acquired in Coleoptera.