From a new, open-access article in the journal Genome Research, “Implications of the first complete human genome assembly” (emphasis added):
Most DNA in the human genome still has unknown functions and is referred to as “genomic dark matter.” Recent work has centered on uncovering key roles for this DNA, which is mainly derived from transposable elements (TEs) that were once mobile and invaded our genome. TEs are now being unveiled to serve not only as gene regulatory elements, but also as self-derived nucleic acids that can be sensed by the human innate immune system to induce anti-viral type I interferons. Assigning function to the dark matter of our genome is a cutting-edge area of research, yet a major caveat in this field is that this enigmatic DNA often lies within unresolved parts of the genome. Genome gaps encompass satellite repeat arrays, ribosomal gene clusters, and regions of segmental duplications that represent an unexplored dimension of human population variation, impacting health and disease. With their highly repetitive nature, unresolved regions are a black box in terms of their sequence and activity. Now, with ultra-long Oxford Nanopore sequencing, the T2T [telomere-to-temlomere] Consortium has been able to resolve gaps even across centromeres that are hotbeds of tandem satellite arrays. In the new T2T complete reference from CHM13hTERT cells with a normal karyotype, repetitive elements are found to comprise more of the genome than previously thought, with satellite and simple repeats particularly underestimated. But do we have evidence that dark matter can contribute to disease variation? Yes, indeed, several recent studies have shed light on how structural variation in TEs impacts on gene expression differences in disease settings. Our own unpublished recent work pinpoints satellite repeat arrays as platforms for the regulation of normal developmental fate transitions. The initial T2T data and follow-up complete assemblies of more genomes will allow us and others to investigate how previously unresolved dark matter DNA can vary in the human population. Studies assessing how repetitive RNA shapes 3D genome organization will also benefit from the resolved T2T reference sequences. Future breakthroughs building on the T2T initiative will ultimately lead to innovative therapies for diverse diseases but will also allow us to understand more broadly how genomes evolve, and how tissue-specific gene expression programs are controlled.
Those are some pretty striking “implications.”
What is amazing, frankly, is how many researchers refuse to listen to the advice of Dan Graur, Joe Felsenstein, Larry Moran, Nick Matzke, John Avise, and T. Ryan Gregory (among others) that the “junk” sequences (e.g., repetitive elements) in the human genome really are just evolutionary detritus. There is no point in investigating those regions for possible functional roles. Let the junk be, to stand forever as evidence of purposeless evolutionary processes, and work on something else.
Nah, say the researchers. Evolutionary debris to you, maybe; unexplored territory to us.