I COVERED on Monday the birth of two new genes via an intragenic inversion, today I will look at a new gene from capture of a gene from a mobile element. The product is a gene found in Old and New World monkeys and apes, but not in prosimians.
First some background. Mobile elements are sequences of DNA carrying genes with instructions for replicating that sequence and splicing it in to a new place in the genome. In doing so they can add DNA to the genome (almost half of our genome is the remnants of transposable elements) or cause mutations. They are described as “selfish” because they do not directly do anything beneficial for the host organism, although some have been “domesticated” to now carry out beneficial tasks. In general their drawbacks seem to outweigh the benefits, since selection seems to favor their aggressive silencing by DNA methylation and similar tactics whenever a new strain pops up. The origin of mobile elements is unclear, but they likely have a common ancestor.1 In this case the mobile element is a type II mobile element, a sequence of DNA that splices itself out of the genome and then splices back in at a different insertion site (this very nice site discusses the activity of transposase with modeling–seems to work well with Firefox, not so well with Explorer). The enzyme required to reinsert is called transposase.
The chimeric gene SETMAR was discovered in 1997 as a combination of a SET domain protein with a transposase from mariner-like Hsmar1 transposon (the MAR part of SETMAR). The SET portion of the protein displays the expected activity in methylating histones, but the function of the MAR portion is uncertain. SETMAR seems to be actively expressed in a wide range of human tissues, suggesting it has an important function that is not yet understood.
As part of this study the authors looked at the genomes of eight different primates to try to find where SETMAR originated. First SET was examined outside the primates and it was found that SET does not occur with a downstream Hsmar1 transposon in other vertebrates, however, a there is a possible Hsmar1 insertion site. The prosimians also do not possess SETMAR, but it is present in both Old and New World monkeys and all apes. This suggests Hsmar1 inserted 40-58 million years ago, before these groups diverged. Soon afterward a 27-bp deletion removed the stop codon on SET. This allows transcription of SET all the way through Hsmar1‘s transposase gene. This merger produced a new intron composed of the sequence between the end of SET and the beginning of MAR. In an additional quirk, at some point about this time another transposable element, AluSx, inserted in the 5′ terminal inverted repeat (TIR) of Hsmar1, deleting 12-bp. This may have facilitated the gene fusion since the TIR’s at both ends of a transposon like Hsmar1 must be intact to allow the transposon to spice back out of the genome and move to a new site. AluSx may have essentially chained Hsmar1 there so it could not escape when SET acquired it. Otherwise the transposon may have spliced out again at some point, leaving some primates with a SETMAR gene and others with a truncated SET.
The N-terminal region of MAR, required in transposase for DNA binding, is highly conserved in all primates bearing it, and appears to be under strong selection. The C-terminal region has a mutation that abolishes transposase activity, and is unable to catalyze transposon integration in in vitro assays. This suggests a new function for SETMAR unrelated to transposon integration. The authors found that SETMAR associates with the TIR of Hsmar1 transposons. In an intact transposase, the protein would bind to the TIR and then splice out the transposon to free it as a loop of DNA. It appears SETMAR associates with TIR, but cannot cut out the transposon. The authors suggest that perhaps SETMAR binds to Hsmar1 transposon TIRs and then the SET region catalyzes the methylation of nearby histones, possibly helping to block the movement of Hsmar1 transposons.
In the first example of unusual gene evolution I discussed an intragenic inversion that converted one gene to two genes that are thought to help regulate the expression of their parent gene’s duplicate. In this case a hijacked transposon gene may be used as a weapon to suppress transposons. In the third case, coming up Thursday, a transposon creates a new gene by retrotransposing an RNA transcript copied from two adjacent genes and then abnormally spliced, accidentally aiding its host.
- Capy, P.; Vitalis, R.; Langin, T.; Higuet, D.; Bazin, C. “Relationships Between Transposable Elements Based Upon the Integrase-Transposase Domains: Is There a Common Ancestor?” Journal of Molecular Evolution 1996, 42, 359-368. DOI:10.1007/PL00006063
- Cordaux, R.; Udit, S.; Batzer, M. A.; Feschotte, C. “Birth of a chimeric primate gene by capture of the transposase gene from a mobile element.” Proceedings of the National Academy of Sciences, USA 2006, 103, 8101-8106. DOI:10.1073/pnas.0601161103