Imagine the human the genome in the form of a string extending the length of a football field, with all the genes that code for proteins clustered together at the end near your feet. Take two big steps forward; all the protein information is now behind you.
The human genome has three billion base pairs in its DNA, but only 2% of them code for proteins. The rest seems to be unnecessary bloat, a profusion of duplicate sequences and genomic dead ends often labeled “unwanted DNA”. This surprisingly thrifty allocation of genetic material is not limited to humans: even many bacteria seem to devote 20% of their genome to the non-coding load.
There are still many mysteries surrounding the question of what non-coding DNA is and whether it really is worthless junk or something more. Parts of it, at least, have been shown to be of vital biological importance. But even beyond the question of its functionality (or lack thereof), researchers are beginning to understand how non-coding DNA can be a genetic resource for cells and a nursery where new genes can evolve.
“Slowly, slowly, slowly, the terminology of ‘unwanted DNA’ [has] started to die, ”said Cristina Sisu, geneticist at Brunel University in London.
Scientists casually referred to “junk DNA” as early as the 1960s, but they took up the term more formally in 1972, when geneticist and evolutionary biologist Susumu Ohno used it to claim that large genomes would inevitably harbor sequences, accumulated passively over many millennia, which did not encode any protein. Shortly thereafter, researchers gained tangible evidence of the abundance of these wastes in genomes, the diversity of their origins, and the amount of these wastes transcribed into RNA despite the lack of blueprints for proteins.
Technological advancements in sequencing, especially over the past two decades, have done a lot to change the way scientists think about non-coding DNA and RNA, Sisu said. Although these non-coding sequences do not carry information about proteins, they are sometimes shaped by evolution for different purposes. Consequently, the functions of the different classes of “trash can” – insofar as they have functions – become more precise.
Cells use some of their non-coding DNA to create a diverse menagerie of RNA molecules that regulate or aid in protein production in a variety of ways. The catalog of these molecules continues to grow, with small nuclear RNAs, microRNA, small interfering RNAs and much more. Some are short segments, typically less than two dozen base pairs long, while others are an order of magnitude longer. Some come in double strand or fold in on themselves in hairpin curls. But all of them can selectively bind to a target, such as a messenger RNA transcript, to promote or inhibit its translation into protein.
These RNAs can have substantial effects on the well-being of an organism. The experimental shutdowns of certain microRNAs in mice, for example, have induced disorders ranging from tremors To liver dysfunction.
By far the largest category of non-coding DNA in the genomes of humans and many other organisms consists of transpose, segments of DNA that can change their location in a genome. These “jumping genes” have a propensity to make many copies of themselves – sometimes hundreds of thousands – across the genome, says Seth Cheetham, geneticist at the University of Queensland in Australia. The most prolific are the retrotransposons, which propagate efficiently by making RNA copies of themselves that convert back to DNA elsewhere in the genome. On half of the human genome is made up of transposons; in some corn plants, this figure jumps to around 90 percent.
Non-coding DNA also appears in the genes of humans and other eukaryotes (organisms with complex cells) in intron sequences that interrupt exon sequences encoding proteins. When genes are transcribed, the RNA from the exon is spliced into mRNA, while much of the RNA from the intron is rejected. But some of the intron RNA can turn into small RNAs that are involved in protein production. Why eukaryotes have introns is an open question, but researchers suspect that introns help speed up gene evolution by making it easier to rearrange exons into new combinations.
The Complex Truth About “Junk DNA”
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