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Given this imprecision, it may be more informative to focus on the biological processes generating orphan genes. When the definition of orphan genes is relaxed such that some sequence similarity of orphans with other genes is permitted, processes like exaptation of transposable elements, gene duplication, and horizontal gene transfer emerge as potential forces underlying the generation of orphan genes []. Genes originating from such processes with detectable sequence similarities are better characterized as young genes and should be clearly distinguished from orphan genes sensu stricto. Mechanisms resulting in true orphans can be placed into four categories, which I outline here. (i) Origin of new genes from previously noncoding DNA – these genes have also been called de novo genes indicating that the ancestral sequence was not functional. (ii) Gene duplication and rapid divergence: either gene duplications or insertions of reverse transcribed mRNA sequences into the genome result in duplications of already existing genes. It has been proposed that duplicated copies may undergo phases of rapid evolution in a combination of neutral and adaptive changes []. This rapid evolution erases the sequence similarity with the other copies, generating an orphan gene. Despite being conceptually appealing, this class of orphan genes is difficult to distinguish from de novo genes because it is very challenging to identify historically rapidly evolving sequences. Hence, I treat this class jointly with de novo genes. (iii) Horizontal gene transfer: integration of foreign DNA from bacteria or viruses into the host genome may result in the acquisition of hitherto absent genes. Given the vast number of viral sequences, it is very likely that the source of the acquired gene has not yet been sequenced. Although this mechanism is prevalent in prokaryotes, based on the current surveys of orphan genes in eukaryotes, very little support for horizontal gene transfer has been found []. (iv) Frameshift mutations (overprinting): N-terminal frameshifts could generate an entirely different protein with almost no change in the protein coding DNA sequence (CDS) []. In viruses, de novo genes are frequently generated without frameshifts in the ancestral gene []. Although up to 7% of the orphan genes may originate by this process [], I suggest their evolutionary dynamics be treated separately because their emergence is frequently coupled with the loss of the progenitor gene.