Creationism in Crisis
Rogue Mitochondrial DNA - Malevolent Intelligence, Incompetence or Mindless Evolution?
Rogue Mitochondrial DNA - Malevolent Intelligence, Incompetence or Mindless Evolution?
Mitochondria surrounded by cytoplasm
Credit: Dr David Furness
Transmission em image of mitochondria
© H. Jastrow.
So often, if only they hadn't learned to ignore it like an elephant in the room, or stay carefully ignorant of it, creationists should be confronting evidence that, if they believe it was designed, could only have been designed by a malevolent or incompetent designer.
Take for example this discovery that sections of mitochondrial DNA (mtDNA) frequently (in about 1 in 4,000 births) cross into the nuclear DNA, where it can cause cancer.
Creationists insist that this must have been intelligently designed by an omniscient designer who would therefore have known the outcome of its designed processes. The presence of mitochondria in cells is of course, good evidence of how simple, prokaryote cells, evolved into more complex, eukaryote cells by endosymbiosis - something creationists insist didn’t happen, so they are already an acute embarrassment for creationists. Now we have this finding that a supposed intelligent design process would look like a design to cause cancer.
This was discovered recently by a team of researchers at the University of Cambridge and Queen Mary University of London. The team were investigating a 2018 claim by researchers at the Cincinnati Children’s Hospital Medical Center in the USA, that there were occasional instances of inheritance of paternal mtDNA, in contradiction to the normally accepted view that mtDNA in inherited exclusively from the maternal line because the sperm head, which fertilizes the egg does not contain any mitochondria.
The Cambridge/London team found that these were in fact examples of the migration of sections of mtDNA into the cell nucleus where they had become incorporated into the nuclear DNA. The process is in theory a two-way process except for two things:
- There is only one nucleus with two copies of the DNA, but a cell can contain thousands of mitochondria, each with a copy of its DNA so the odds are greatly in favour of sections of mtDNA becoming free-roaming.
- The nuclear membrane has pores which allow RNA to pass out into the cell, whereas the mitochondrial membrane is an intact barrier through which DNA or RNA can't normally pass.
Scientists have shown that in one in every 4,000 births, some of the genetic code from our mitochondria – the ‘batteries’ that power our cells – inserts itself into our DNA, revealing a surprising new insight into how humans evolve.
In a study published today in Nature, researchers at the University of Cambridge and Queen Mary University of London show that mitochondrial DNA also appears in some cancer DNA, suggesting that it acts as a sticking plaster to try and repair damage to our genetic code.Mitochondrial DNA appears to act almost like a Band-Aid, a sticking plaster to help the nuclear genetic code repair itself. And sometimes this works, but on rare occasions if might make things worse or even trigger the development of tumours.
Professor Patrick F. Chinnery, senior author
Department of Clinical Neuroscience
School of Clinical Medicine, University of Cambridge, Cambridge, UK
Mitochondria are tiny ‘organelles’ that sit within our cells, where they act like batteries, providing energy in the form of the molecule ATP to power the cells. Each mitochondrion has its own DNA – mitochondrial DNA – that is distinct to the rest of the human genome, which is comprised of nuclear DNA.
Mitochondrial DNA is passed down the maternal line – that is, we inherit it from our mothers, not our fathers. However, a study published in PNAS in 2018 from researchers at the Cincinnati Children’s Hospital Medical Center in the USA reported evidence that suggested some mitochondrial DNA had been passed down the paternal line.
To investigate these claims, the Cambridge team looked at the DNA from over 11,000 families recruited to Genomics England’s 100,000 Genomes Project, searching for patterns that looked like paternal inheritance. The Cambridge team found mitochondrial DNA ‘inserts’ in the nuclear DNA of some children that were not present in that of their parents. This meant that the US team had probably reached the wrong conclusions: what they had observed were not paternally-inherited mitochondrial DNA, but rather these inserts.
Now, extending this work to over 66,000 people, the team showed that the new inserts are actually happening all the time, showing a new way our genome evolves.Billions of years ago, a primitive animal cell took in a bacterium that became what we now call mitochondria. These supply energy to the cell to allow it to function normally, while removing oxygen, which is toxic at high levels. Over time, bits of these primitive mitochondria have passed into the cell nucleus, allowing their genomes to talk to each other.
This was all thought to have happened a very long time ago, mostly before we had even formed as a species, but what we've discovered is that that’s not true. We can see this happening right now, with bits of our mitochondrial genetic code transferring into the nuclear genome in a measurable way.
Our nuclear genetic code is breaking and being repaired all the time. Mitochondrial DNA appears to act almost like a Band-Aid, a sticking plaster to help the nuclear genetic code repair itself. And sometimes this works, but on rare occasions if might make things worse or even trigger the development of tumours.
Professor Patrick F. Chinnery
The team estimate that mitochondrial DNA transfers to nuclear DNA in around one in every 4,000 births. If that individual has children of their own, they will pass these inserts on – the team found that most of us carry five of the new inserts, and one in seven of us (14%) carry very recent ones. Once in place, the inserts can occasionally lead to very rare diseases, including a rare genetic form of cancer.
It isn’t clear exactly how the mitochondrial DNA inserts itself – whether it does so directly or via an intermediary, such as RNA – but Professor Chinnery says it is likely to occur within the mother’s egg cells.
When the team looked at sequences taken from 12,500 tumour samples, they found that mitochondrial DNA was even more common in tumour DNA, arising in around one in 1,000 cancers, and in some cases, the mitochondrial DNA inserts actually causes the cancer.
More than half (58%) of the insertions were in regions of the genome that code for proteins. In the majority of cases, the body recognises the invading mitochondrial DNA and silences it in a process known as methylation, whereby a molecule attaches itself to the insert and switches it off. A similar process occurs when viruses manage to insert themselves into our DNA. However, this method of silencing is not perfect, as some of the mitochondrial DNA inserts go on to be copied and move around the nucleus itself.
The team looked for evidence that the reverse might happen – that mitochondrial DNA absorbs parts of our nuclear DNA – but found none. There are likely to be several reasons why this should be the case.I am so delighted that the 100,000 Genomes Project has unlocked the dynamic interplay between mitochondrial DNA and our genome in the cell’s nucleus. This defines a new role in DNA repair, but also one that could occasionally trigger rare disease, or even malignancy.
Professor Sir Mark J. Caulfield, co-author
Vice Principal for Health
William Harvey Research Institute,
Queen Mary University of London, London, UK
Firstly, cells only have two copies of nuclear DNA, but thousands of copies of mitochondrial DNA, so the chances of mitochondrial DNA being broken and passing into the nucleus are much greater than the other way around.
Secondly, the DNA in mitochondria is packaged inside two membranes and there are no holes in the membrane, so it would be difficult for nuclear DNA to get in. By contrast, if mitochondrial DNA manages to get out, holes in the membrane surrounding nuclear DNA would allow it pass through with relative ease.
The team’s findings are available in their open access paper in Nature:
AbstractI wonder if any creationists are ever going to address the question of why they would rather we saw their putative designer god as either malevolent or incompetent, or both, rather than have people accept that these sorts of problems are the work of a mindless, natural, utilitarian process - evolution, just as science says. But then they have a hidden agenda that requires fools to believe falsehoods, so you can be sure that creationists are either frauds or fools.
DNA transfer from cytoplasmic organelles to the cell nucleus is a legacy of the endosymbiotic event—the majority of nuclear-mitochondrial segments (NUMTs) are thought to be ancient, preceding human speciation1,2,3. Here we analyse whole-genome sequences from 66,083 people—including 12,509 people with cancer—and demonstrate the ongoing transfer of mitochondrial DNA into the nucleus, contributing to a complex NUMT landscape. More than 99% of individuals had at least one of 1,637 different NUMTs, with 1 in 8 individuals having an ultra-rare NUMT that is present in less than 0.1% of the population. More than 90% of the extant NUMTs that we evaluated inserted into the nuclear genome after humans diverged from apes. Once embedded, the sequences were no longer under the evolutionary constraint seen within the mitochondrion, and NUMT-specific mutations had a different mutational signature to mitochondrial DNA. De novo NUMTs were observed in the germline once in every 104 births and once in every 103 cancers. NUMTs preferentially involved non-coding mitochondrial DNA, linking transcription and replication to their origin, with nuclear insertion involving multiple mechanisms including double-strand break repair associated with PR domain zinc-finger protein 9 (PRDM9) binding. The frequency of tumour-specific NUMTs differed between cancers, including a probably causal insertion in a myxoid liposarcoma. We found evidence of selection against NUMTs on the basis of size and genomic location, shaping a highly heterogenous and dynamic human NUMT landscape.
Wei, W., Schon, K.R., Elgar, G. et al.
Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes. Nature 611, 105–114 (2022). https://doi.org/10.1038/s41586-022-05288-7
Copyright: © 2023 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
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