Scientists Found a Hidden Code in the Human Genome
Around 45 percent of human DNA is made up of transposable elements, or TEs—genetic leftovers from now-extinct viruses that scientists once believed to be 'junk DNA.'
But that view is changing, and a new study—which grouped TEs based on evolutionary relationships and level of conservation—found that one family of sequences known as MER11 plays a role in gene expression.
Nearly 80 years after their initial discovery, scientists are still finding new things about how TEs play a vital role in primate evolution.
Ever since Swiss physician Friedrich Miescher first isolated DNA back in 1869, science has been on an incredible path of genomic discovery. One of the major moments in the journey occurred in the 1940s, when cytogeneticist Barbara McClintock discovered transposable elements (TE), also known as 'jumping genes.' Decades later, The Human Genome Project found that these elements made up a staggering 45 percent of the human genome, and managed to proliferate over millions of years thanks to a 'copy-and-paste' mechanism.
Because these sequences are highly repetitive and nearly identical, they've been disregarded as 'junk DNA' for decades—genetic leftovers from long-extinct viruses. But in recent years, this unflattering view of these sequences has begun to change. Today, scientists believe that TEs play a role in genome function, chromosome evolution, speciation, and diversity. However, due to their repetitive nature, TEs remain difficult to research.
Now, a new international study has found a novel method for analyzing these mysterious sequences, and they've discovered hidden patterns responsible for gene expression. The results of the study were published in the journal Science Advances.
'Our genome was sequenced long ago, but the function of many of its parts remain unknown,' Fumitaka Inoue, a co-author of the study from Kyoto University, said in a press statement. Understanding TEs would solve one of the biggest mysteries of the genome.
In an attempt to better understand TEs, the researchers developed a new method for classifying them. Eschewing standard annotation tools, this study groups TEs based on both their evolutionary relationships and their conservation quality in the primate genome. Focusing on a family of sequences called MER11, the new method allowed scientists to divide the group into subgroups, named MER11_G1 through G4. The G1 subgroup represented the oldest evolutionary sequences, while G4 contained the youngest.
By looking at MER11 through this new lens, researchers were able to compare these new subfamilies with epigenetic markers, and found that these groups appeared to have a regulatory function within the genome. In other words, they acted like on-off switches for gene expression—particularly in early human development.
Of course, it's one thing to infer a pattern, and another to see it in action. So, the team used a technique known as 'lentiviral massively parallel reporter assay,' or lentiMPRA, to measure 7,000 MER11 sequences using human stem cells and early-stage neural cells. This showed that the youngest of the group (MER11_G4) had the strongest impact on gene expression. According to the study, this group makes use of regulatory 'motifs'—short stretches of DNA that influence gene development and response.
By tracking the evolution of this group, scientists have shown that DNA originally inherited from ancient viruses can actively participate in the form and function of primate DNA. Even though the journey of understanding the human genome is more than 150 years in the making, it still has the remarkable ability to surprise us at seemingly every turn.
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