<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>The genome sequences completed so far contain more than 20 000 genes with unknown function and no similarity to genes in other genomes. The origin and evolution of the
orphan genes is an enigma. Here, we discuss the suggestion that some orphan genes
may represent pseudogenes or short fragments of genes that were functional in the
genome of a common ancestor. These may be the remains of unsuccessful duplication
or horizontal gene transfer events, in which the acquired sequences have entered the
fragmentation process and thereby lost their similarity to genes in other species. This
scenario is supported by a recent case study of orphan genes in several closely related
species of <italic>Rickettsia</italic>, where full-length ancestral genes were reconstructed from sets
of short, overlapping orphan genes. One of these was found to display similarity to
genes encoding proteins with ankyrin-repeat domains.</p>
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Comp Funct Genomics. 2003 Oct; 4(5):537-541