The term “pseudogene” was coined by Jacq and colleagues in 1977. The standard tale of biologists dogmatically ignoring possible functions of noncoding DNA would have it that such a sequence automatically would be dismissed as “junk” when discovered, especially since the notion of a degraded and now non-coding former gene matches Ohno’s concept of “junk DNA” as originally proposed. The reality is that Jacq et al. (1977) did consider whether the sequence had a function, but based on the available data they concluded that the best explanation is that it is “an evolutionary relic”. They did not cite Ohno.
The 5S DNA of Xenopus laevis, coding for oocyte-type 5S RNA, consists of many copies of a tandemly repeated unit of about 700 base pairs. Each unit contains a “pseudogene” in addition to the gene. The pseudogene has been partly sequenced and appears to be an almost perfect repeat of 101 residues of the gene. The order of components in the repeat unit is (5′) long spacer-gene-linker-pseudogene (3′) in the “+” strand (or H strand) of the DNA. The possible function of the pseudogene is discussed.
The functions of the different regions of the 5S DNA are only imperfectly understood. The gene region 1-121 codes for the mature oocyte 5S RNA, and the presence of a pppG sequence at residue 1 of the mature 5S RNA defines this residue as the point of initiation of transcription by RNA polymerase III (Roeder, 1976). The point of termination of transcription, however, is less clear. Brown and Brown (1976) have argued that the high A + T-rich sequence of residues 119-123 of the gene region is a signal for the termination of transcription. But low yields of a larger transcription product–about 135 residues long–have been isolated by Denis and Wegnez (1973) in pulse-labeling experiments in Xenopus laevis oocytes. Similar length molecules have also been isolated in heat-shocked Drosophila cells by Rubin and Hogness (1975). While clear evidence that these 135-long molecules are precursors of the mature 5S RNA in Xenopus (or Drosophila) is lacking, their isolation clearly demonstrates that longer transcripts may be synthesized in vivo. It is therefore possible that the structural gene for 5s RNA is larger than the 121 residues of the mature 55 RNA and extends into the region of DNA, linking gene and pseudogene for at least another 15 residues.
Thus the known transcription of the 5S DNA system does not explain the presence of the pseudogene. Moreover, no RNA products corresponding to the pseudogene have been isolated, although it is conceivable that these may well have been overlooked or confused with tRNA in earlier studies (Denis and Wegnez, 1973), especially if they occur only in low yield. We are thus forced to the conclusion that the most probable explanation for the existence of the pseudogene is that it is a relic of evolution. During the evolution of the 5S DNA of Xenopus laevis, a gene duplication occurred producing the pseudogene. Presumably the pseudogene initially functioned as a 5S gene, but then, by mutation, diverged sufficiently from the gene in its sequence so that it was no longer transcribed into an RNA product.
This evolutionary explanation for the presence of the pseudogene, however, is incomplete by itself in that it ignores the conservation in sequence of the pseudogene, and indeed of the entire G + C-rich spacer of 5S DNA. In an attempt to explain this, it has been suggested (Brownlee, 1976) that the pseudogene may be a “transcribed spacer” corresponding to a primary transcript of 5s RNA, which is a transient precursor and has not been detected. If this is so, then most of the G + C-rich region of 5S DNA would be the structural gene for 5S RNA. This function, if true, would provide the necessary selective pressure to conserve the sequence of the “linker” and pseudogene region so that the correct processing of the postulated 300-long precursor was maintained. In the absence of any experimental evidence for such a long precursor, however, this suggestion must be regarded as speculative; it is more probable that the pseudogene is a relic of evolution.
Part of the Quotes of interest series.
Jacq, C., J.R. Miller, and G.G. Brownlee. 1977. A pseudogene structure in 5S DNA of Xenopus laevis. Cell 12: 109-120.