F Rosa Rubicondior: Creationism in Crisis - How De Novo Genes Arise (And Another Creationist Dogma Bites The Dust)

Saturday 9 December 2023

Creationism in Crisis - How De Novo Genes Arise (And Another Creationist Dogma Bites The Dust)


New genes can arise from nothing | HiLIFE – Helsinki Institute of Life Science | University of Helsinki

Present a creationist with a puzzle like, where does new genetic information in the form of new functional genes come from and a typical response will be, "Er... I can't imagine how that's possible... so God did it!". This of course is based on the foundational fallacies of creationism, and most religious apologetics - the argument from ignorant incredulity, and the false dichotomy fallacy.

This intellectual dishonesty appeals to people who are satisfied with not knowing and aren't bothered about the truth, so long as they have an excuse for pretending they know the answer

By contrast, present a scientist with the same question, and the response will probably be, "I don't know, so how can we find out?", because admitting ignorance is the foundation of good science. This approach appeals to people who have the humility to admit they don't know and who are interested enough in truth to want to find out.

An example of this was published recently by three researchers from the Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland, who decided to address the question of where de novo genes arise in the genome, seemingly from nowhere.

This question arose from the observation that a comparison between human and other primate genomes shows that a number of microRNA (miRNA) sequences arose within the human genome, and the genome of other apes apparently as single mutation events.

In addition to the 20,000 genes in the human genome, there are thousands of miRNA sequences of about 22 base-pairs which have a regulatory function. Their role is to stop messenger RNA (mRNA) from continuing to make proteins when enough have been made. They do this by blocking the mRNA molecules and to do this they need to be folded in half like a hairpin. This folding means that they need to be 'palindromes', i.e., reading the same forward as backward, so, when folded in half, each base lines up with a copy of itself.

So, the question was, how do these palindrome miRNAs arise?

A creationist like Michael J. Behe or William Dembski would look at that and try to calculate the probability of the second 11 bases in a 22-base miRNA molecule exactly matching the reverse of the first 11 and conclude that it is so unlikely that it can't have happened by chance and can't account for so many examples of them in the genome. But of course, they are using the wrong mathematical model. It doesn't happen by a sequence of random chances. In fact, it turned out that it is remarkably easy and not as highly unlikely as creationist frauds will tell their dupes, because of the way RNA is built from a DNA template, the availability of non-coding DNA, the fact that mistakes are frequent, and the way DNA comes in a double helix where one strand is the mirror image of the other.

Given those conditions, which are normal in a eukaryote cell, the production of these palindromic miRNAs is not improbably small, it's certain. In fact, it's inevitable.

Researchers studied an error mechanism in DNA replication, and noticed that some errors create palindromes that can fold into hairpin structures.

Credit: Ari Löytynoja
The transcription starts at one end and travels along until it encounters an error. Transcription them switches to the opposite strand, which is a mirror image of the length just transcribed and continues backwards, so creating a palindromic strand of RNA. Far from being highly unlikely, its actually certain from the way DNA is structured.

As the Helsinki University news release explains:
All RNA molecules require palindromic runs of bases that lock the molecule into its functional conformation. Importantly, the chances of random base mutations gradually forming such palindromic runs are extremely small, even for the simple microRNA genes. Hence, the origin of these palindromic sequences has puzzled researchers. Experts at the Institute of Biotechnology, University of Helsinki, Finland resolved this mystery, describing a mechanism that can instantaneously generate complete DNA palindromes and thus create new microRNA genes from previously noncoding DNA sequences.

In a project funded by the Academy of Finland, researchers studied errors in DNA replication. Ari Löytynoja, the project leader, compares DNA replication to typing of text.

DNA is copied one base at a time, and typically mutations are erroneous single bases, like mis-punches on a laptop keyboard. We studied a mechanism creating larger errors, like copy-pasting text from another context. We were especially interested in cases that copied the text backwards so that it creates a palindrome.

Ari Löytynoja, corresponding author
Institute of Biotechnology
Helsinki Institute of Life Science,
University of Helsinki, Helsinki, Finland.
Researchers recognised that DNA replication errors could sometimes be beneficial. They described these findings to Mikko Frilander, an expert in RNA biology. He immediately saw the connection to the structure of RNA molecules.

In an RNA molecule, the bases of adjacent palindromes can pair and form structures resembling a hairpin. Such structures are crucial for the function of the RNA molecules.

Mikko J. Frilander, co-author
Institute of Biotechnology
Helsinki Institute of Life Science
University of Helsinki, Helsinki, Finland
Researchers decided to focus on microRNA genes due to their simple structure: the genes are very short – just a few tens of bases – and they have to fold into a hairpin structure to function correctly.

The whole genome of tens of primates and mammals is known. A comparison of their genomes reveals which species have the microRNA palindrome pair, and which lack it. With a detailed modelling of the history, we could see that whole palindromes are created by single mutation events. The emergence of new genes from nothing has fascinated researchers. We now have an elegant model for the evolution of RNA genes.

Heli A. M. Mönttinen, lead author
Institute of Biotechnology
Helsinki Institute of Life Science
University of Helsinki, Helsinki, Finland
A central insight was to model the gene history using a custom computer algorithm. According to postdoctoral researcher Heli Mönttinen, this enables the closest inspection of the origin of genes thus far.

By focusing on humans and other primates, researchers in Helsinki demonstrated that the newly found mechanism can explain at least a quarter of the novel microRNA genes. As similar cases were found in other evolutionary lineages, the origin mechanism appears universal.

In principle, the rise of microRNA genes is so easy that novel genes could affect human health. Heli Mönttinen sees the significance of the work more broadly, for example in understanding the basic principles of biological life.

Although the results are based on small regulatory genes, researchers believe that the findings can be generalised to other RNA genes and molecules. For example, by using the raw materials generated by the newly found mechanism, natural selection may create much more complex RNA structures and functions.
Sadly, the paper in PNAS is behind paywall, but the statement of significance and the abstract are available under a Creative Commons license:
Significance

The emergence of novel genes from previously nonfunctional sequence has gained significant attention, but the mechanisms behind this process have remained elusive. MicroRNA (miRNA) genes are one of the simplest forms of genetic information and their transcripts fold into a short stem-loop structure to yield 22-nt gene products that suppress mRNA targets. While some miRNA genes are ancient, new genes also appear to emerge de novo. Here, we show that template switching in DNA replication can form perfect base pairing for a stem structure with a single mutation event and has participated in the emergence of nearly 20 human miRNA genes. Being a relatively high-frequency mechanism, template switching provides raw material for evolution and allows for near-instant rewiring of genetic information and rapid adaptation to changing environments.

Abstract

The mechanisms generating novel genes and genetic information are poorly known, even for microRNA (miRNA) genes with an extremely constrained design. All miRNA primary transcripts need to fold into a stem-loop structure to yield short gene products ( 22 nt) that bind and repress their mRNA targets. While a substantial number of miRNA genes are ancient and highly conserved, short secondary structures coding for entirely novel miRNA genes have been shown to emerge in a lineage-specific manner. Template switching is a DNA-replication-related mutation mechanism that can introduce complex changes and generate perfect base pairing for entire hairpin structures in a single event. Here, we show that the template-switching mutations (TSMs) have participated in the emergence of over 6,000 suitable hairpin structures in the primate lineage to yield at least 18 new human miRNA genes, that is 26% of the miRNAs inferred to have arisen since the origin of primates. While the mechanism appears random, the TSM-generated miRNAs are enriched in introns where they can be expressed with their host genes. The high frequency of TSM events provides raw material for evolution. Being orders of magnitude faster than other mechanisms proposed for de novo creation of genes, TSM-generated miRNAs enable near-instant rewiring of genetic information and rapid adaptation to changing environments.

Structured, functional de novo genes arising spontaneously from nowhere by an inevitable natural process destroys yet another creationist argument from ignorant incredulity combined with their favourite false dichotomy fallacy. In fact, it is so commonplace that it accounts for the 'evolvability' of species in response to changing environments over time, where de novo advantageous genes just appear to have arisen when needed, as though something is guiding evolution.

Of course, only the advantageous ones survived the assortative sieve of natural selection.

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