<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>ORFans are open reading frames (ORFs) with no detectable sequence similarity
to any other sequence in the databases. Each newly sequenced genome contains a
significant number of ORFans. Therefore, ORFans entail interesting evolutionary
puzzles. However, little can be learned about them using bioinformatics tools, and
their study seems to have been underemphasized. Here we present some of the
questions that the existence of so many ORFans have raised and review some of
the studies aimed at understanding ORFans, their functions and their origins. These
works have demonstrated that ORFans are an untapped source of research, requiring
further computational and experimental studies.</p>
[]
Comp Funct Genomics. 2003 Jul; 4(4):432-441