Understanding mutations and selection

This was prompted by a post in the “Examples of irreducible complexity?” thread; to avoid starting a rabbit trail there I’m starting this.

Here’s what I wrote there:

Thinking of mutations and the large stretches of non-coding DNA, have there been examples of a mutation in a stretch of that “silent” DNA turning a section into coding DNA?

Sort of like if we have the sequence STQCK and the Q gets changed to an A and it becomes STACK – a meaningless string converted to one with meaning.

  • An initial google search into the basic question: “What is coding DNA?” took me straight away to: Difference between Coding and Noncoding DNA.
  • BJU’s introduction quickly convinced me that the subject matter is significantly above my beginner’s ability to digest.

You jumped straight to dessert!! :wink:

There are a few things that need to happen before we can get to the potential function of a new protein.

Before we get to protein translation (RNA to protein) we need RNA transcription (DNA to RNA). In order for DNA to be transcribed into a meaningful amount of RNA there needs to be an upstream sequence of DNA that promotes the binding of RNA polymerase and other transcription factors. This promoter sequence is relatively easy to evolve since they are short sequences with relaxed sequence requirements. ENCODE was able to find them throughout the genome in non-functional DNA, and we would expect them to emerge even from random sequence.

With RNA alone you may have a functional gene. RNA can interact with other RNA transcripts in a functional manner. However, there are still a lot of RNA transcripts that are non-functional as newly evolved transcription sites come and go.

If the RNA transcript also has sequences that cause splicing (e.g. U1 snRNP sites), then this can promote export from the nucleus out into the cytoplasm where it can be translated into protein. Future mutations to the coding region of this newly evolved coding gene can be accessible to natural selection down the road. Not only will changes to amino acids have an impact, but so too will mutations that get rid of stop codons and increase the length of protein.


See also De novo gene birth - PMC for a review.
There is a large gray area in which it’s unclear whether something is actually a new gene or not. It’s not that uncommon for random stretches of DNA to start being translated into peptides. The trick is figuring out which of them are actually doing something useful, even if in a small way; those are the ones that are likely to stick around, but that may only be clear in hindsight.

Many are transcribed but few are translated. Many are translated but few are selected.


So say a new sequence has appeared and in such a way that it gets translated. Does that result in a new protein being turned out in the cell, with no use at the time? and cells may ‘find’ a use for such later?

It could have an immediate use or not. However, there is a stronger selective pressure against non-functional proteins than there is against non-functional DNA or non-functional RNA. A single messenger RNA can produce thousands of protein molecules, each of which come at a cost of energy. Replicating and maintaining a few thousand bases of DNA costs very little energy, and RNA is still not that costly for a eukaryotic cell. Both of these will fall below what is called the drift barrier, the level at which the cost can be seen by selection. It’s covered in this quite interesting paper (IMHO):


From what I can tell, if that protein is going to have function it needs to find it quick (in evolutionary terms). It’s kind of the poop or get of the pot moment.

Okay, but every protein was once a new protein with no function, right?

Not really. Many, probably most, proteins were once a different protein with a different function. Gene duplication gave a second copy that could then acquire a new function via mutation.

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I would think most are older proteins which developed a different function through mutation, perhaps with that function being minimal at first then subsequent mutations made it more active/functional.

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But if you go back far enough there must have been a first protein, and all the rest came along later.

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good question–well, I look forward to what others say, but as proteins are made from amino acids–it’s really interesting what happened first–and with the miracle of transcription, how that did happen–I am not implying irreducible complexity, just intrigue and interest.

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It may have been one protein or a set of proteins. Some have speculated that the first set of proteins functioned to stabilize the activity of ribozymes, as one example. However, this would be deep, deep into history, probably around 3.5 to 4 billion years ago. At the same time, the birth of new proteins during this early history could have been similar to how new proteins emerge now, by the expression of previously non-coding DNA.


Yes – intuition (mine at least) says that during the period of abiogenesis and immediately following the genes were RNA sequences and some primitive collection of RNAs cooperated as the first ribosomes.
RNAs are delicate, hence any proteins that resulted from mRNAs of that gene sequence would be rare in the sense that a stamp with the biplane turned upside down is rare in philately, and in fact all such proteins would be rare. The link from a serendipitous usefulness of a protein to extra copies of the gRNA (Gene RNA) that generated mRNAs is fuzzy, but such a link necessarily did/does exist.
Just as a First Cell is difficult to picture, Jack Szostak (PhD, Nobel Medicine 2009, now at the University of Chicago) has sketched out quite a bit of that image. In time one might hope for some of his grad students to focus on this.

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The big question I have is where the first cell wall came from. RNA floating around loose is just chemistry; it needs at the very least some membrane keeping it in a safe place. I presume the first membrane was a cell wall, so how did that happen and have the RNA and such inside?

The first “cell wall” was made with fatty acids and was permeable. It simply “growed” like Topsy in Uncle Tom’s Cabin. There were also RNAs. A synergy existed between, (a) RNAs that made more RNAs, and (b) cell walls that were made with some phospholipids. That synergy led to the rise of RNAs that copied lots of other RNAs, and cell walls made with lots of phospholipids.
So far so good - the real breakthroughs in this field belong to Jack Szostak, PhD, Nobel, Medicine, 2009. He was recruited to the faculty of the University of Chicago in September 2022 to pursue the study of how abiogenesis was likely to have happened. Lacking God’s touch, it did happen. Long rationale skipped here that concludes the universe would be less than utterly perfect if abiogenesis were impossible thus life needed a jump-start on every suitable planet.
In other words Szostak has demonstrated the above as a valid scientific hypothesis and was recruited to the U of Chicago to focus on further research into the field currently called OOL for Origin Of Life.

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