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Shake and Bake Neanderthal

Lets make some old friends.
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OK, so we've sequenced the neanderthal genome.

99.7% of the nucleotide sequences of the modern human and Neanderthal genomes are identical, compared to humans sharing around 98.8% of sequences with chimps.

The proportion of Neanderthal-inherited genetic material is about 1.5 to 2.1 % & is found in all non-African populations. It is suggested that 20 % of Neanderthal DNA survived in modern humans.

It's a good bet we'll find some of their genome that didn't survive in modern humans in chimps, other apes & probably elsewhere (we're 40-50% cabbage after all).

So with CRISPR gene editing all we have to do is find the gene sequences we want edit some human DNA & inject it into a hollowed out ovum.

We know modern humans could interbreed so a surrogate mother to bring it to term isn't going to be a problem.

There may be a small problem with miscarriage for male neanderthal carried by a modern human but we've immunosuppressant drug treatments that can solve that, or we just produce some females first & use some of them to carry the first males.

You know, I think we can do this.

Skewed, May 31 2020

Neanderthal genetics https://en.wikipedi...eanderthal_genetics
WikipediA [Skewed, May 31 2020]

Neanderthal genome project https://en.wikipedi...thal_genome_project
WikipediA [Skewed, May 31 2020]

CRISPR gene editing https://en.wikipedi...CRISPR_gene_editing
WikipediA [Skewed, May 31 2020]

CRISPR https://en.wikipedia.org/wiki/CRISPR
WikipediA [Skewed, May 31 2020]

Modern humans may have miscarried male hybrids https://www.science...g-babies-here-s-why
Here's why. [Skewed, May 31 2020]

Stiggins http://en.wikipedia...artholomew_Stiggins
[kdf, May 31 2020]

Jurassic Park https://jurassicpar...0sex%20and%20breed.
Filling in the gaps [kdf, Jun 02 2020]

Whole 3 billion letters of Neanderthal genome sequenced https://www.genome....al-genome-sequenced
in 2010 [Skewed, Jun 03 2020]

Neanderthal mitochondrial DNA sequenced https://www.nature....human%20neighbours.
in 2008 [Skewed, Jun 03 2020]

People aren't bananas https://www.newscie...rts%20in%20bananas.
Letter on the misleading nature of reports of genetic differences [Loris, Jun 15 2020]

[link]






       [marked-for-deletion]
because resurrecting extinct species is already widely discussed in science and science fiction literature. My favorites resurrected Neanderthal is probably Bartholomew Stiggins in Jasper Fforde’s “Thursday Next” series. (link)
  

       From the help file: “... inventions for the halfbakery should be original to the poster...” and [mfd] reasons include wishing something you saw in a movie, book, etc existed in real life.
kdf, May 31 2020
  

       What do you do with the baby once she is born? It would be no use raising her in a middle-class developed-world household.   

       Yet we don't yet know enough about palaeolithic culture, language, and social development norms and practices... do we?   

       Perhaps give her to an "untouched" tribe in the Amazon rainforest, or the New Guinea highlands. But then when she is grown how do we keep track of her and study her? Would we then learn more than if we just studied her foster-siblings, and save money on all the genetic engineering?   

       Or do we raise her in a zoo, with animatronic neanderthal carers, and invented synthetic palaoelithic languages and behavioural norms?
pocmloc, May 31 2020
  

       Reminds me of 'The Ugly Little Boy'. I don't think it'd be a problem particularly though, because our cultures overlapped at the time. They also had jewellery and cave art. The issue would probably be an unfamiliar form of neurodiversity, but parents deal with that all the time, and parenthood is rarely something one is prepared for. You just deal with the new person without previous experience because everyone is already unique.
nineteenthly, May 31 2020
  

       23andme already has a tool to find other people with high % Neanderthal admixture. Let 21st century nature take its course for a dozen generations and soon a Neanderthal population might reemerge naturally.
sninctown, May 31 2020
  

       Baked - see current occupant of Whitehouse.
xenzag, May 31 2020
  

       //resurrecting extinct species is already widely discussed in science and science fiction literature//   

       Half baked for a certainty, in general principles, yes.   

       But.   

       //should be original to the poster//   

       Show me anywhere else where's it been suggested we source our DNA building blocks to make a Neanderthal from cabbages ;p
Skewed, Jun 02 2020
  

       Perhaps I've been remiss in not showcassing the core idea as clearly as I might.   

       Let me try again.   

       Old fossil DNA is very broken up & damaged causing difficulties in stitching it back together into something that can be used by an egg cell (a la standard documented & replicated cloning techniques) to produce a useful organism.   

       So don't try to do that.   

       Use living DNA instead.   

       & jigsaw the genome you want together from living DNA extracted from extant animals & even plants.   

       I don't myself recall seeing that proposed as a technique for restoring extinct species in any prior art.   

       But I doubt I'm ahead of the curve & stand ready to be corrected :)
Skewed, Jun 02 2020
  

       "old fossil DNA is broken up... so use living DNA instead & jigsaw the genome you want together from living DNA extracted from extant animals & even plants. ... don't myself recall seeing that proposed as a technique for restoring extinct species in any prior art."   

       Michael Crichton's Jurassic Park (link) - they used what little undamaged dinosaur DNA they could, filled in the blanks from frogs and other extant species.
kdf, Jun 02 2020
  

       //filled in the blanks from frogs// a phrase with up to unlimitless usability
pocmloc, Jun 02 2020
  

       //filled in the blanks//   

       I stand corrected, but I do think it might be fair to say I've gone a bit further than that with stitch it 'all' together from extant animals & plants?
Skewed, Jun 03 2020
  

       //I wonder if dinosaurs taste like chicken//   

       Nope, like frogs, which don't actually taste entirely like chicken, speaking from personal experience.. though, maybe if I'd cooked them first..
Skewed, Jun 03 2020
  

       There's problems with all this %similarity stuff. Simplistic at best. I've never read what it's really even based upon. The problem with generating a new & functional neandathal genome starts with knowing quite a lot about it. Once you have a good idea from several samples, you can start to be confident about the primary sequence. Then you can start to build epigenetic maps like has already been started. But you need to be confident about the effects of time and degradation on all of those.   

       They already have the neanderthal mitochondrial genome, that's pretty interesting. A human cell with neanderthal mitochondria is very possible and would be pretty interesting to study if, crucially, the money is available.   

       I guess you could carefully assemble the neanderthal genome, section by section, or, mutate the human one, section by section, but it's a HUGE job. Far easier to wait for custom synthesis to get to the point of whole chromosomes. Still enormously tricky to get that primary sequence all wound up and viable in a cell. There's 10 years of work there before you go into the ethical nightmare of getting a viable embryo.
bs0u0155, Jun 03 2020
  

       Umm.. I was under the impression that we'd already sequenced the full genome not just the mitochondria [bs0]?   

       Have I fallen afoul of hyperbole?   

       [Googles]   

       Umm, nope <linky> <linky.   

       3 billion letters, the whole thing, & that was 10 years ago, we got the mitochondria sequenced 2 years b4 that.   

       Point is there's only a 0.3% disparity between it & the human genome so all we need to do is jigger that 0.3%.   

       20% of that 0.3% can be found spread around in the non- african population.   

       So that leaves us 0.24% to locate in other extant animals & plants (or synthesize from basic DNA 'letters') & splice in with CRISPR.   

       Plus the mitochondria which I assume has similarly minor differences to ours.   

       I think your data may be a little dated [bs0]?   

       Or did I misunderstand your thinking?
Skewed, Jun 03 2020
  

       Oh sequencing, sure. We can sequence whole genomes for a couple of thousand dollars now. (Actually, I should check if it's exome or real whole genomes) The problem is that 0.3% of 3 billion bases is an awful lot of mutations, most of which will be spread around randomly, many won't do anything. The problem is doing all the edits, CRISPR can do it, slowly. But it's maybe 10,000 separate edits and screens? That's a HUGE job.
bs0u0155, Jun 04 2020
  

       //HUGE job//   

       No doubt, thought it would be, but very plausibly doable now.
Skewed, Jun 04 2020
  

       //...But I doubt I'm ahead of the curve & stand ready to be corrected :)//   

       Stand By For Action!   

       //Old fossil DNA is very broken up & damaged causing difficulties in stitching it back together into something that can be used by an egg cell (a la standard documented & replicated cloning techniques) to produce a useful organism.
So don't try to do that.
Use living DNA instead & jigsaw the genome you want together from living DNA extracted from extant animals & even plants.
I don't myself recall seeing that proposed as a technique for restoring extinct species in any prior art.//
  

       I think the main problem here is that the way you're imagining that people would go about such a task is very much not how anyone who was working in the field would consider going about doing it.   

       I mean, saying that "Old fossil DNA is very broken up & damaged" and that this might cause "difficulties in stitching it back together" is a bit of an understatement.
You know how some of the materials in old cars can be salvaged, and the first stage of this is putting it through a car shredder?
I suggest that it would be easier to rebuild the exact model of a car from the shreddings of several similar cars than to try to physically reconstruct an ancient genome using only ancient DNA.
And if you want it to actually be the genome of a living cell... well, there's more issues there. And more if you want it to develop into an organism.
  

       //So with CRISPR gene editing all we have to do is find the gene sequences we want edit some human DNA & inject it into a hollowed out ovum.//   

       That's not how CRISPR gene editing works actually. You've conflated a couple of things there.
CRISPR lets you make an edit to a DNA sequence using an RNA template. Not replace it at the scale of entire chromosomes. (It's also my understanding that with the current state of the art, there's also a down-side in that there's a tendency to introduce off-target mutations, which is obviously not desirable in a massive conversion process such as this.)
I think you're mixing this with the reproductive technology of "somatic cell nuclear transfer" - in which a cell nucleus is implanted into an enucleated egg cell. Currently it's not a technique with a high success rate.
  

       Obviously it would be theoretically possible to use these techniques sequentially, and a rather convoluted process involving these (and much more) seems to me more plausible than trying to work up fossil DNA directly - but I hesitate to call it trivial.
A couple of years ago there was some furore when a Chinese group claimed to have successfully gene-edited twin human girls. (for information search for the lead scientist involved "He Jiankui".) It's not clear whether this was actually true or not - papers were rejected on ethical grounds. And the modification doesn't actually seem relevant to the medical case.
But it's clear that people have considered doing more significant germ-line modification - hell, I've mentioned it on here fairly recently. At the point where gene-editing is ready for the big time, I hope we'll be willing to use it.
Although- I must confess I'm very interested in seeing how you get ethical approval for winding someone's children back to the stone age.
Loris, Jun 07 2020
  

       Mainly this is a bump, to solicit a reaction to the above. But also:   

       //There's problems with all this %similarity stuff. Simplistic at best. I've never read what it's really even based upon.//   

       I think this should be said explicitly, and perhaps less diplomatically.   

       Have you seen pop-sci articles, or heard people claim something like ~'humans are 50% similar to bananas'~?   

       There was probably some research which did indeed report that similarity (or even, sometimes, identity). But without details of the comparison, it's at best meaningless, and at worst misleading.   

       There's many things that could mean. Is it a comparison of proportion of somewhat-similar genes they have in common? It it a comparison of the sequence of specific genes, or their cognate protein sequences? If so, what was the comparison algorithm : was it pairwise or multi-alignment? How did it extract the sequences which were compared? If you don't have at least approximate indications for these, there just isn't enough context to understand the result. See the link I've added.   

       So basically, one current typical approach is to identify one or several genes present in all organisms of interest. The more evolutionarily related the group, the larger the set could be. In the modern era, one can easily extract genes from a draft genome, but historically matching regions could be isolated and sequenced.
However you've got them, you need to compare 'em somehow. If we're looking at rather unrelated organisms, the DNA won't be that similar, so it makes sense to translate that to get the protein sequences. This increases similarity in a couple of ways - introns are naturally discarded, and all codon variations are stripped. You may even count different amino-acids as similar. Nevertheless, some of the sequence won't match at all - or at least, not convincingly - and these ranges may be discarded from the analysis. How to deal with insertions or deletions? One approach is to ignore them! If you're doing a multiple alignment, the more variable regions will probably end up totally clipped away.
Regardless, the bits which are left have an overall similarity, which can be gleefully reported in misleading pop-sci articles without any of the boring technical details.
Of course this varies depending on which genes (or set of genes) you compare and the alignment algorithm you use.
Also of course, whatever the value is isn't at all a measure of overall similarity, or of evolutionarily relevant divergence, only of relatedness of the parts which have a chance of being similar.
  

       A somewhat historically used approach was microarrays, but my experience seeing those in action wasn't flattering, and as far as I care all such data is obsolete now, if it wasn't at the time of generation.   

       An even older technique was to hybridise DNA from two organisms and examine heteroduplexes by EM or so. I think most groups doing this probably knew what they were doing and were quite careful because it must've been a royal pain to do - but even so it probably generated a lot of gee-whizz pop-sci factorrhea.   

       Another approach is just to count genes which appear somewhat similar as the same, and see what proportion are shared. Obviously this also has implementation details - but even disregarding those, if the result is cited without mention of the method, you can achieve impressive levels of similarity.
Loris, Jun 15 2020
  

       //Mainly this is a bump, to solicit a reaction to the above//   

       [Sniggers]   

       [Remains otherwise silent]
Skewed, Jun 23 2020
  
      
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