A groundbreaking study involving human cells infused with plant DNA has shed light on the ongoing debate regarding the functionality of large portions of the human genome. Researchers at the University of Auckland, led by Brett Adey and Austen Ganley, have discovered that significant segments of the non-coding DNA in these hybrid cells exhibit activity nearly equivalent to that of human DNA. This finding raises questions about the notion that much of the human genome serves a critical purpose.
The research, reported in New Scientist, indicates that what was previously considered “junk DNA” may account for a significant portion of genomic activity. The study utilized cells containing DNA from the plant species Arabidopsis thaliana, revealing that the plant DNA was not only present but also functional, despite being randomly integrated into human cells. “A large amount can simply be explained by background noise,” says Adey. “This seems to be broadly consistent with the junk DNA idea.”
The primary role of DNA is to encode the information necessary for producing proteins, which perform various essential functions within the cell. Historically, it was believed that nearly all DNA encoded for proteins. However, modern understanding reveals that only about 1.2 percent of the human genome directly encodes proteins. This raises the question: what does the remaining DNA do?
Since the 1960s, many biologists have supported the theory that a substantial portion of non-coding DNA is functionally irrelevant. For example, a study published in 2011 indicated that only around 5 percent of the genome is conserved throughout evolutionary history, suggesting that much of the DNA lacks significant functional relevance.
In contrast, proponents of the idea that non-coding DNA has undiscovered functions refer to it as “dark DNA.” This term was popularized by the ENCODE project, which in 2012 asserted that more than 80 percent of the human genome is active, hinting at potential functions not yet understood. In response, Sean Eddy of Harvard University proposed the concept of a “random genome project,” suggesting that inserting synthetic random DNA into human cells would still yield significant activity, thereby questioning the conclusions drawn by ENCODE.
Adey and Ganley saw an opportunity to test this hypothesis when they learned of hybrid cells containing 35 million base pairs of plant DNA. This represents the largest random genome project conducted to date, given that the divergence between plants and animals occurred over 1.6 billion years ago, effectively randomizing much of the non-coding DNA in the plant genome.
After confirming the randomness of the plant DNA, the researchers measured the number of transcription start sites—indicators of DNA being converted to RNA—per 1000 base pairs of non-coding DNA. Surprisingly, they found that approximately 80 percent as many start sites existed in the plant DNA compared to human non-coding DNA. This strongly indicates that much of the activity observed by ENCODE may, in fact, be inconsequential.
“This is an excellent demonstration of how biology is, indeed, noisy,” states Chris Ponting from the University of Edinburgh. “The biochemical activities happening within this [plant] sequence clearly confer no function on the human cell.”
The research team acknowledges that while their findings point toward the predominance of “noise” in the genome, they also observed about 25 percent more activity in human DNA compared to the plant DNA. Ganley notes, “All we can really say is that that needs explanation.” The team is currently exploring potential functions of these additional RNA molecules, although they emphasize that this would not alter the overall conclusion regarding the majority of non-coding DNA.
In summary, the study provides compelling evidence supporting the notion that much of the human genome may be less functional than previously believed. By leveraging hybrid cells as a novel means of exploration, researchers continue to challenge established perceptions of genomic activity and its implications for our understanding of genetics. The results, while still pending formal publication, may significantly influence ongoing discussions surrounding the human genome and its complexities.
