How we lost our tails (new preprint)

Most primates have tails, but us humans and the other apes (chimps, gorillas, orangutans, and gibbons) are all tail-less. Clearly, having tails was the ancestral primate condition, so how did apes (AKA hominoids) end up losing their tails?
Screenshot 2021-09-17 at 00.54.36

Earlier today a new preprint was released at least partially answering this question:

The paper is well written and IMO very accessible to non-specialists, so I’d recommend checking it out. I’ll summarise it briefly though…

To look for the genetic basis of the loss of tails, the authors started with a list of 31 genes known to be involved in tail development from mouse studies. First, they looked for any protein-coding mutations that might disrupt the ape homologs of these 31 genes, but didn’t find any promising candidates. So they looked at the non-coding sequences.

They found an ape-specific insertion of a ~300bp Alu element in the 6th intron of a gene called TBXT. The image below shows UCSC genome browser tracks of the alignment between a much of primate genomes, with the apes on top. Basically, the black regions show conserved sequence compared to humans, so the white column in the alignment of the non-ape sequences with humans represents a gap where the non-ape primates lack this insertion, implying it occurred only in the last common ancestor of apes, after they diverged from the other primates.

How does this affect the function of the gene? It wasn’t immediately obvious, until the authors noticed that another Alu element (AluSx1) was present nearby in intron 5 in all primate genomes. They hypothesised that these two Alu sequences, being very similar, could bind to each other in the single-stranded transcript, forming a stem and loop structure. This would disrupt the normal splicing of the transcript, excising exon 6 from the mature transcript, producing a different transcript isoform and therefore the resulting protein would be missing 58 amino acid residues from this exon sequence.

Indeed, they identified this transcript in human embryonic cell populations and then used CRISPR deletions of the Alu elements to show that they were the cause of this transcript, as the isoform failed to be produced without those Alu elements.

Screenshot 2021-09-17 at 01.03.11

Finally, they used CRISPR to delete exon 6 of TBXT in mice, and found that heterozygotes for this mutation tended to have short or missing tails.
Screenshot 2021-09-17 at 01.10.18
This wasn’t a fully penetrant phenotype - some mutants showed perfectly normal tails, so it is a variable phenotype that was likely stabilised by other mutations in the course of early ape evolution.

The partial inactivation of TBXT functionality by the loss of exon 6 from the transcript has severe (lethal) consequences in homozygous mouse mutants, suggesting the selection pressure must have been quite strong in the ape common ancestor to keep this mutation around. Alternatively, the genetic background of the ape ancestor may have happened to be more permissive to this mutation than in mice. Further studies of this mutation in a primate context would be interesting, although challenging.

I think this study is an instant classic. Simple experiments, clearly communicated, and impactful.


I laugh imagining modern humans with fully formed tails. Imagine @John_Harshman with a tail :laughing:

@Eddie, I guess this will interest you since you claim to be deeply interested in how these sort of morphological changes happen.


Fascinating. So, if I’m understanding this correctly, this shows that (at least quite plausibly) a single event (specifically an insertion of a certain length of DNA) resulted in an individual with a genome capable of producing a tail-less phenotype? And then this mutation spread through the population, perhaps accumulating some other mutations which helped to stabilize and increase the chance of viability of this phenotype?

And because this insertion was of a transposable element in a non-coding region, it isn’t like this is some kind of freakishly improbable event - it could have occured just about anywhere in that particular stretch of DNA (i.e. didn’t have to occur at a specific base pair), and these TEs move around the genome through mechanisms we understand.


Yep. Interestingly this same type of mutation, a transposable element insertion into an intron, is also responsible for the evolution of the dark peppered moth phenotype during the industrial revolution.


Did anyone catch the theodicy question in this paper? It seems that the genetic process of tail less humans lead to malformations of the spinal cord similar to spina bifida in humans.


What I find very interesting is how often transposable elements play a major role in evolutionary change. I think most people don’t realize how important stuff like ERVs, Alus are in evolution. Cool to know I lost my tail cause of an Alu insertion.


Yes, I noticed that, though to be honest it didn’t seem particularly notable to me. I.e., it’s another instance of the problem of (natural) evil but doesn’t stand out over other generic instances like the existence of disease, etc.


How “we” lost our tails? When did humans ever have tails?

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“We” is a clade of primates of which humans are found among. So “we” that lost “our” tails are all those species of primates who descent from that last tailless common ancestor. Chimpanzees, Orangutans, Humans, Gorillas, Gibbons, and so on.


What fossil evidence is there of the gradual loss of the tail in some primates? Let me guess … there is none.

Here the evidence is genetic. It’s no surprise that apes do not have tails, this paper is describing what makes that difference.

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Nobody says it was “gradual”, as this single mutation appears to be able to make the organism completely lose it’s tail. The oldest tailless primate fossils are younger than the oldest tailed primate fossils, so this transition is in fact supported by fossil chronology.


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