Junk DNA is gradually making its way into mainstream textbooks

The idea that most of the human genome is junk originated more that 50 years ago. Since then, evidence in support of this concept has steadily accumulated but it has been stongly resisted by most biochemists and molecular biologists. Opposition is even stronger among scientists in other fields and in the general public thanks to a steady stream of anti-junk articles in the popular press.

Much of this opposition to junk DNA stems from a massive publiciy campaign launched by ENCODE researchers and the leading science journals back in 2012.

It's likely that most of the controversy over junk DNA is related to differing views on evolution and the power of natural selection. Most people think that natural selection is very powerful so that modern species must be extremely well-adapted to their present environment. They tend to believe that complexity is simply a reflection of sophisticated fine-tuning and this must apply to the human genome. According to this view, the presence of huge amounts of DNA with an unknown function is just a temporary situation and in the next few years most of this 'dark matter' will turn out to have a function. It has to have a function otherwise natural selection would have eliminated it.

Most experts in molecular evolution reject this view. They are quite comfortable with the concept of a messy genome full of junk DNA because that fits with their view of evolution—a view that was shaped by the development of neutral theory and nearly-neutral theory in the late 1960s and early 1970s. This view—the messy genome view—has not been covered in most biochemistry and molecular biology textbooks and this partially explains why recent generations of scientists are so committed to the sophisticated fine-tuning view of genomes.

I'm pleased to report that this may be changing. Many teachers and textbook writiers are beginning to realize that the evidence for junk DNA and a messy genome is too overwhelming to ignore so they have to address it in their books. Hopefully, this will soon make its way into the classroom.

The latest edition of Molecular Biology of the Cell is a good example of this change. The authors of the 7th (2022) edition are: Bruce Alberts, Rebecca Heald, Alexander Johnson, David Morgan, Martin Raff, Keith Roberts, and Peter Walter. The various authors have always expressed support for the idea that only 10% of the human genome is functional but in earlier editions they avoided the words "junk DNA." They now realize that they need to be more forceful in supporting good genome science so this is what they say in the latest edition.

The power of this [sequence alignment] can be increased by including in such comparisons the genomes of large numbers of species whose genomes have been sequenced such as rat, chicken, fish, dog, and chimpanzee, as well as mouse and human. By revealing in this way the results of a very long natural "experiment," lasting for hundreds of millions of years, such comparative DNA sequencing studies have highlighted some of the most interesting regions in our genome. The comparisons reveal that about 4.5% of the human genome consists of multi-species conserved sequence. To our great surprise only about one fourth of these sequences code for proteins. Most of the remaining conserved sequences consist of DNA that is thought to contain clusters of protein-binding sites involved in gene regulation, while others produce RNA molecules that are not translated into protein but are important for other reasons.

When the DNA sequences of hundreds of thousands of individual humans are compared, an additional 5% of our genome shows a reduced variation in the human population, which implies that sequences in this 5% of the genome are also important. Taken together, these analyses suggest that only about 10% of the human genome contains nucleotide sequences that truly matter.

The important question of how much of the DNA sequence of the human genome is functionally relevant was briefly confused by a set of high-profile publications that appeared in 2012 from a large, federally funded US genome project named ENCODE. These publications, which reported the results of a massive survey using sensitive assays that can detect the presence of RNA molecules in cells at extremely low levels, reported that 76% of the total DNA sequence in human cells is transcribed to produce RNA molecules. Even though many of these transcripts were found at levels of less than a single RNA molecules per cell, the ENCODE scientists used such data to assert that most of human DNA is functional, with very little "junk." This claim received widespread publicity, along with their belief that our genome contains tens of thousands of previously undetected genes that produce RNA molecules that do not code for protein.

As previously stated, there is strong scientific consensus that most of the human genome consists of DNA whose nucleotide sequence is not relevant to biological function—being the so-called junk. This conclusion rests on the finding that natural selection fails to preserve the sequences in the face of the inevitable random changes to genomes that occur over time, as can be seen both when different species are compared and from detailed analyses of human variation. The fact that these DNA sequences nevertheless produce an occasional RNA molecule can be explained by the occurrence of background "noise" in gene expression. Although gene expression is very accurate, it is not perfect, and biochemical errors occasionally occur. Such errors are to be expected, and so long as they are kept at a low level, they are thought to have little or no consequence for the cell.

It's not perfect but it's a good start.

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