Ok, so this was another fascinating article about transposons, my favorite “junk DNA.” After the thread I most recently started, now I’m very curious how you feel about what these scientists said about “junk DNA.”
But I’m also very interested in the science too if you have any comments about that!
Colleague and co-senior author Ting Wang, the Sanford and Karen Loewentheil Distinguished Professor of Medicine in the Department of Genetics at the Washington University School of Medicine in St. Louis, Missouri, agrees.
“The real significance of this story is it tells us how evolution works in the most unexpected manner possible,” Wang said. “Transposons were long considered useless genetic material, but they make up such a big portion of the mammalian genome. A lot of interesting studies illustrate that transposons are a driving force of human genome evolution. Yet, this is the first example that I know of where deletion of a piece of junk DNA leads to a lethal phenotype, demonstrating that the function of specific transposons can be essential.”
The finding could have implications for human infertility. According to first author Andrew Modzelewski, a UC Berkeley postdoctoral fellow, nearly half of all miscarriages in humans are undiagnosed or don’t have a clear genetic component. Could transposons like this be involved?
“If 50% of our genome is non-coding or repetitive—this dark matter—it is very tempting to ask the question whether or not human reproduction and the causes of human infertility can be explained by junk DNA sequences,” he said.
Retrotransposons mediate gene regulation in important developmental and pathological processes. Here, we characterized the transient retrotransposon induction during preimplantation development of eight mammals. Induced retrotransposons exhibit similar preimplantation profiles across species, conferring gene regulatory activities, particularly through long terminal repeat (LTR) retrotransposon promoters. A mouse-specific MT2B2 retrotransposon promoter generates an N-terminally truncated Cdk2ap1 ΔN that peaks in preimplantation embryos and promotes proliferation. In contrast, the canonical Cdk2ap1 peaks in mid-gestation and represses cell proliferation. This MT2B2 promoter, whose deletion abolishes Cdk2ap1 ΔN production, reduces cell proliferation and impairs embryo implantation, is developmentally essential. Intriguingly, Cdk2ap1 ΔN is evolutionarily conserved in sequence and function yet is driven by different promoters across mammals. The distinct preimplantation Cdk2ap1 ΔN expression in each mammalian species correlates with the duration of its preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence.