Is “Pseudogene” a Misnomer?
The term “pseudogene” may be as inappropriate as the term “junk DNA,” according to the entry on pseudogenes in the 2010 Encyclopedia of Life Sciences, published by prestigious the academic publisher John Wiley & Sons. Written by researchers Ondrej Podlaha and Jianzhi Zhang at UC Davis and the University of Michigan, Ann Arbor, respectively, the entry includes a subjection titled “Difficulty with the Pseudogene Definition,” and it states that the discovery of multiple functional pseudogenes should negate the standard presumption that pseudogenes are functionless junk DNA:
The term ‘pseudogene’ was originally coined to describe a degenerated RNA- or protein-coding sequence that is incapable of being transcribed or translated into functional RNA or protein products. The key in this definition is that pseudogenes are biologically nonfunctional. However, in practice, it is virtually impossible to experimentally establish nonfunctionality; the lack of any observable phenotypic effect upon the deletion of a putative pseudogene does not necessarily mean that the deletion has no phenotypic effect, because the effect may be too subtle to observe. When more and more research groups are coming across cases where a so-called pseudogene is potentially involved in a meaningful biological interaction, primarily in gene regulation (Tam et al., 2008; Watanabe et al., 2008), it becomes increasingly difficult to define pseudogenes. Is it appropriate to call such noncoding yet functional sequences pseudogenes? This is where the boundaries of the pseudogene definition become hazy.
(Ondrej Podlaha and Jianzhi Zhang, “Pseudogenes and Their Evolution,” Encyclopedia of Life Sciences (John Wiley & Sons, 2010).)
They further explain that even the observation that a particular “pseudogene” is not transcribed into RNA is not sufficient to demonstrate that it is non-functional:
Furthermore, although most examples of ‘functional pseudogenes’ involve some interactions between the pseudogene transcript and the mRNA of the functional paralog, pseudogenes have also been found to function in ways that do not require transcription, such as serving as the material source of gene conversion events to enhance the antibody diversity in birds, humans and other vertebrates
(Ota and Nei, 1995; Balakirev and Ayala, 2003).
They recommend finding new terminology for pseudogenes with a function, to avoid the “the ‘functional pseudogene’ oxymoron.”