Year: 2022

DECODING JUNK DNA. "In a paper published in Nature in 2012, ENCODE researchers concluded that 80% of the human genome is functional. Ever since, commentators have argued over what large swaths of non-coding DNA might be doing. Super-enhancers, which can occupy tens of kilobases, suggest a use for at least some of this DNA. In fact, published ENCODE work foreshadowed the super-enhancer discovery." https://lnkd.in/ezRUFD5 View in LinkedIn

80% FUNCTIONAL? "These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions.” As a very small fraction of the genome (~1%) encodes for protein sequences, a question in science has been, what does the other 99% do? ENCODE data demonstrated that much of this DNA participates in biochemistry in some way." https://lnkd.in/e-NRQHx View in LinkedIn

ENCODE definition of functional proteins includes those that are "biochemically functional" even if it had no impact on phenotype. This definition has been challenged by others. https://lnkd.in/eJne7Xw View in LinkedIn

ONLY 8.2% FUNCTIONAL? " From extrapolations we estimate that 8.2% (7.1–9.2%) of the human genome is presently subject to negative selection and thus is likely to be functional. Nearly 99% of the human genome does not encode proteins, and while there recently has been extensive biochemical annotation of the remaining noncoding fraction, it remains unclear whether or not the bulk of these DNA sequences have important functional roles." (Oxford study). https://lnkd.in/eMD6XXb View in LinkedIn

OXFORD DEFINITION. "The Oxford researchers want to count as “functional” only DNA involved in shaping a person’s body and behavior–the phenotype, DNA that is acted upon by natural selection." https://lnkd.in/eExYi3R View in LinkedIn

8.2% OR 80% FUNCTIONAL? "We do not know enough about gene regulation, epigentic imprinting, and chromatin dynamics to even say how much of the genome is superfluous. I would venture to guess that much of the genome is designed to regulate the complex processes of cell-type specific gene expression and embryonic development." https://lnkd.in/e_se8kz View in LinkedIn

PARTIAL ANSWER. "Even the ENCODE project, looked at a relatively small number of cell types. There are many transient progenitor cell populations whose epigentic marks are not yet described. So I really would not waste much thought about whether it is 8% or 80% functional. I would say there is likely to be remnants of DNA from transposons, gene duplications, pseudogenes etc. But how much of this is truly non-functional remains unknown." https://lnkd.in/e_se8kz View in LinkedIn

BOTH AND? " Who’s correct? It’s possible–in fact, it’s likely–that both groups are. It depends on what is meant by the word “functional.” The explanation seems to be that, while some 80 percent of our DNA is doing stuff, less than 10 percent of it is doing such important stuff that natural selection has preserved it largely intact in the mammal line for 100 million years. (Anatomically modern humans — that’s all 7 billion of us, the last Homo standing — have only been around for a couple of hundred thousand years.)" https://www.geneticliteracyproject.org/2014/08/05/how-much-of-human-dna-is-doing-something/ View in LinkedIn

THE REAL MESSAGE. "The Oxford researchers are saying that only a small proportion of our genome, less than a tenth, is so crucial to our existence that natural selection weeds out injurious mutations and works hard to keep it mostly intact." https://www.geneticliteracyproject.org/2014/08/05/how-much-of-human-dna-is-doing-something/ View in LinkedIn

OXFORD AND ENCODE TO AGREE. "They believe the ENCODE folks would largely agree. “We don’t think our figure is actually too different from what you would get looking at ENCODE’s bank of data using the same definition for functional DNA,” says joint senior author Chris Ponting of the MRC Functional Genomics Unit at Oxford." https://www.geneticliteracyproject.org/2014/08/05/how-much-of-human-dna-is-doing-something/ View in LinkedIn