Small open reading frames: beautiful needles in the haystack

The completion of genome sequences from model organisms creates new opportunities and resources for both basic and applied research. The genome sequence of several bacterial genomes as well as Saccharomyces cerevisiae represent landmark achievements. The total genome sequence era offers many opportunities to explore the wealth of information contained within a genome, but it is also one of the most challenging phases for researchers and emphasizes a need for global approaches to study biological problems. One of these challenges is identifying and defining very small protein-coding genes, which can easily escape detection because they are "buried" in an enormous pile of meaningless short ORFs. Yet the subset of small, functional ORFs (here abbreviated smORFs) probably encode very interesting proteins in all organisms, including humans.