Jul 13, 2024 06:16 PM
https://aeon.co/essays/we-need-new-metap...of-biology
EXCERPTS: . . . The conventional narrative in biology – the one that gets taught at school – goes like this. Our DNA contains lots of genes, which are segments of that molecule for which the sequence encodes a corresponding building-block sequence of proteins, which are chains of amino acids. (The genetic code specifies the translation between DNA sequence and protein sequence.) The genes are read out by being first transcribed into molecules called RNA, with a very similar chemical makeup to DNA, and then these RNA molecules are translated into proteins. Most of those proteins are enzymes, which facilitate biochemical reactions. In this way, the proteins are the molecular workhorses that – in a complicated process still not fully understood – put together new cells and allow embryos to grow and develop into babies. Thus, the genome contains the information needed to make a human.
If a gene acquires a mutation in its sequence – a change to one or more of its chemical letters – it encodes a slightly altered protein. We all have such variations in our genome, and most don’t significantly alter the protein’s ability to do its job. But sometimes a mutation will result in a malfunctioning protein – and that can cause real problems, as it does, for example, with certain mutations to the gene called CFTR that is associated with cystic fibrosis. To understand health conditions with an inherited aspect due to genetic mutations, therefore, we should start by identifying the relevant gene(s).
It is RNA and not DNA that is ‘the computational engine of the cell’
This story is (for the most part) not wrong. It’s plenty good enough to give students a rough notion of how biology works. But its elisions, omissions and simplifications can create serious misconceptions about what genes are and do. Consider this, for instance: most of the regions of the human genome that have been linked to diseases aren’t parts of genes at all. They feature in so-called non-coding sequences.
Only around 1-2 per cent of the entire human genome actually consists of protein-coding genes. The remainder was long thought to be mostly junk: meaningless sequences accumulated over the course of evolution. But at least some of that non-coding genome is now known to be involved in regulating genes: altering, activating or suppressing their transcription into RNA and translation into proteins. Many disease-linked regions are in these regulatory sequences, where mutations don’t change the proteins themselves but, rather, the rate or chance of them being made at all. So, to understand how life really works at the genomic level, we need to understand gene regulation. And that, as we’ll see, is not just eye-wateringly complicated but not at all what we have learnt to expect from the conventional molecular biology of the past 50 years.
What’s more, it turns out that not all genes encode proteins. In fact – and this may be one of genetics’ best-kept secrets, having been discovered only during the past decade – most of them do not. When the HGP began, many experts estimated the number of human genes to be around 100,000. It was soon found that, in fact, we have just 20,000 or so (some estimates put the figure even lower), which is little more than half as many as the banana. Meanwhile, researchers began to find genes that never get translated into protein at all. They are only transcribed into RNA, which seemed to have some intrinsic function rather than merely acting as a messenger for making proteins.
At first these non-coding (nc) RNA genes (they are not literally non-coding, but simply not protein-coding – biology’s language often reveals its flawed preconceptions) seemed a mere curiosity. But their numbers have been growing sharply, and now slightly exceed the number of coding genes. Some predict that eventually ncRNA genes will turn out to far outnumber protein-coding genes. The ncRNAs themselves may vary hugely in length, from many hundreds of ‘letters’ to a mere 20 or so. It is not yet known what many of them do, but in general they are thought to play important roles in gene regulation. As the molecular biologists Kevin Morris and John Mattick wrote:
As Mattick pithily puts it, it is RNA and not DNA that is ‘the computational engine of the cell’.
[...] If that’s so, why haven’t we heard more about it? [...] Part of the reason is that science is inherently and necessarily conservative: slow and reluctant to change its narratives and metaphors, not least because we have all (scientists and public alike) got accustomed to the old ones. And we have yet to find compelling new stories to replace them...(MORE - missing details)
EXCERPTS: . . . The conventional narrative in biology – the one that gets taught at school – goes like this. Our DNA contains lots of genes, which are segments of that molecule for which the sequence encodes a corresponding building-block sequence of proteins, which are chains of amino acids. (The genetic code specifies the translation between DNA sequence and protein sequence.) The genes are read out by being first transcribed into molecules called RNA, with a very similar chemical makeup to DNA, and then these RNA molecules are translated into proteins. Most of those proteins are enzymes, which facilitate biochemical reactions. In this way, the proteins are the molecular workhorses that – in a complicated process still not fully understood – put together new cells and allow embryos to grow and develop into babies. Thus, the genome contains the information needed to make a human.
If a gene acquires a mutation in its sequence – a change to one or more of its chemical letters – it encodes a slightly altered protein. We all have such variations in our genome, and most don’t significantly alter the protein’s ability to do its job. But sometimes a mutation will result in a malfunctioning protein – and that can cause real problems, as it does, for example, with certain mutations to the gene called CFTR that is associated with cystic fibrosis. To understand health conditions with an inherited aspect due to genetic mutations, therefore, we should start by identifying the relevant gene(s).
It is RNA and not DNA that is ‘the computational engine of the cell’
This story is (for the most part) not wrong. It’s plenty good enough to give students a rough notion of how biology works. But its elisions, omissions and simplifications can create serious misconceptions about what genes are and do. Consider this, for instance: most of the regions of the human genome that have been linked to diseases aren’t parts of genes at all. They feature in so-called non-coding sequences.
Only around 1-2 per cent of the entire human genome actually consists of protein-coding genes. The remainder was long thought to be mostly junk: meaningless sequences accumulated over the course of evolution. But at least some of that non-coding genome is now known to be involved in regulating genes: altering, activating or suppressing their transcription into RNA and translation into proteins. Many disease-linked regions are in these regulatory sequences, where mutations don’t change the proteins themselves but, rather, the rate or chance of them being made at all. So, to understand how life really works at the genomic level, we need to understand gene regulation. And that, as we’ll see, is not just eye-wateringly complicated but not at all what we have learnt to expect from the conventional molecular biology of the past 50 years.
What’s more, it turns out that not all genes encode proteins. In fact – and this may be one of genetics’ best-kept secrets, having been discovered only during the past decade – most of them do not. When the HGP began, many experts estimated the number of human genes to be around 100,000. It was soon found that, in fact, we have just 20,000 or so (some estimates put the figure even lower), which is little more than half as many as the banana. Meanwhile, researchers began to find genes that never get translated into protein at all. They are only transcribed into RNA, which seemed to have some intrinsic function rather than merely acting as a messenger for making proteins.
At first these non-coding (nc) RNA genes (they are not literally non-coding, but simply not protein-coding – biology’s language often reveals its flawed preconceptions) seemed a mere curiosity. But their numbers have been growing sharply, and now slightly exceed the number of coding genes. Some predict that eventually ncRNA genes will turn out to far outnumber protein-coding genes. The ncRNAs themselves may vary hugely in length, from many hundreds of ‘letters’ to a mere 20 or so. It is not yet known what many of them do, but in general they are thought to play important roles in gene regulation. As the molecular biologists Kevin Morris and John Mattick wrote:
It appears that we may have fundamentally misunderstood the nature of the genetic programming in complex organisms because of the assumption that most genetic information is transacted by proteins. This … is turning out not to be the case in more complex organisms, whose genomes appear to be progressively dominated by regulatory RNAs.
As Mattick pithily puts it, it is RNA and not DNA that is ‘the computational engine of the cell’.
[...] If that’s so, why haven’t we heard more about it? [...] Part of the reason is that science is inherently and necessarily conservative: slow and reluctant to change its narratives and metaphors, not least because we have all (scientists and public alike) got accustomed to the old ones. And we have yet to find compelling new stories to replace them...(MORE - missing details)