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Intergenic Retrotransposons Can Serve Long-Range Functions

Jonathan McLatchie

Retrotransposons (which include LINEs, SINEs, and ERVs) are known for the ability of their long-terminal repeats (LTRs) to serve as promoters and enhancers for regulating the expression of genes that are immediately downstream (Conley et al., 2008; Dunn et al., 2005). The majority of retrotransposons, however, are located considerable distances from genes (often hundreds of kilobases away) — and this has often been taken as evidence that the majority of these retrotransposons are, in fact, non-functional.

But can these retrotransposons serve long-range functions that do not require them to be in close proximity to genes? An interesting 2010 paper, published in PNAS, examined an intergenic LTR retrotransposon, ERV-9 (which is “located 40-70kb upstream of the human fetal ?- and adult ?-globin genes”), to determine whether it “serves a host function in regulating transcription of the far downstream globin genes” (Pi et al., 2010). The authors “generated transgenic (Tg) mice carrying the entire 100-kb human globin gene locus with or without ERV-9 LTR.” The study showed that “an LTR retrotransposon of ERV-9 human endogenous retrovirus located 40-70kb upstream of the human fetal ?- and adult ?-globin genes serves a long-range, host function.”

The paper explains:

The ERV-9 LTR contains multiple CCAAT and GATA-2 present in low abundance in adult erythroid cells to assemble an LTR/RNA polymerase II complex. The LTR complex transcribes intergenic RNAs unidirectionally through the intervening DNA to loop with and modulate transcription factor occupancies at the far downstream globin promoters, thereby modulating globin gene switching by a competitive mechanism.

This study underscores again what we have been emphasizing for a while: it is still very premature, to say the least, for partisans of “junk DNA” to be declaring that the preponderance of our genome is junk. This is particularly true given the rate at which function is being identified for the non-coding portions of our genome.

Jonathan McLatchie

Fellow, Center for Science and Culture
Dr. Jonathan McLatchie holds a Bachelor's degree in Forensic Biology from the University of Strathclyde, a Masters (M.Res) degree in Evolutionary Biology from the University of Glasgow, a second Master's degree in Medical and Molecular Bioscience from Newcastle University, and a PhD in Evolutionary Biology from Newcastle University. Currently, Jonathan is an assistant professor of biology at Sattler College in Boston, Massachusetts. Jonathan has been interviewed on podcasts and radio shows including "Unbelievable?" on Premier Christian Radio, and many others. Jonathan has spoken internationally in Europe, North America, South Africa and Asia promoting the evidence of design in nature.

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