Genetic features known as transposons make up a large portion of many mammalian genomes, including humans', and they are now known to play a variety of roles. Some transposable elements (TEs) could be the remnants of ancient viruses. There are many leftover TEs in the human genome, and its thought that they used to be able to move or jump around the genome, (and they are sometimes known as jumping genes), but most are now thought to have lost that ability. These sequences are typically highly repetitive and many do not code for protein; as such, they are hard to sequence, and were once written off as junk DNA. But in recent years, advancements in genetic technology have allowed researchers to learn more about this 'dark' region of the genome.
The study of these mysterious genetic features has shown that many TEs have important regulatory functions. New research has confirmed this, and has revealed that a group of DNA sequences known as MER11 can control gene expression. The findings have been reported in Science Advances.
Repetitive sequences can be very challenging to sequence and study, and many TEs are also very similar, adding another challenge. But this work overcame those difficulties to show that in primate genomes, there are four unique groups of MER11 sequences: MER11_G1, _G2, _G3, and _G4. The MER11_G4 is the youngest, from an evolutionary perspective.
The investigators compared these groups to epigenetic markers. Epigenetics refers to genetic features that can change gene expression without altering the DNA sequence, such as chemical tags like methyl groups. The comparison showed that the behaviors of MER11 subfamilies align with gene regulation.
But the scientists also wanted to directly test the ability of the MER11 groups to control gene expression. They developed an assay to compare DNA sequences, to assess how they each affect gene activity. This technique was applied to stem or neural cells, which were exposed to about 7,000 MER11 sequences from different primates and humans.
The effort demonstrated that MER11_G4 could exert a strong effect on gene expression. There are also regulatory sequences in MER11_G4 where molecules that have a dramatic effect on gene activity, known as transcription factors, can bind. These regulatory sequences, or binding motifs, can have a major impact on how genes react to signals from the cell or environment.
“Young MER11_G4 binds to a distinct set of transcription factors, indicating that this group gained different regulatory functions through sequence changes and contributes to speciation,” noted first study author Dr. Xun Chen.
The study has shown how different non-coding DNA sequences can have a major influence on biology. By tracing how they change in different species, scientists can also show how they have shaped evolution.
"Our genome was sequenced long ago, but the function of many of its parts remain unknown," said co-corresponding study author Dr. Fumitaka Inoue. More of its mysteries will be revealed as scientists, with the proper support, can advance genetic technologies and knowledge.
Sources: Kyoto University, Science Advances