This article beautifully explains "how" hominoids c 25 Ma lost the tail.
The "why" is easier: they became bipedal in flooded/mangrove forests: wading upright + climbing arms overhead, google our TREE paper "Aquarboreal Ancestors".
The genetic basis of tail-loss evolution in humans and apes
Bo Xia cs 20121
https://doi.org/10.1101/2021.09.14.460388
The loss of the tail is one of the main anatomical evolutionary changes to have occurred along the lineage leading to humans & the “anthropomorphous apes”.
This morphological re-programming in the ancestral hominoids has been long considered to have accommodated a characteristic style of locomotion, and contributed to the evolution of bipedalism in humans.
Yet, the precise genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown.
Primate genome sequencing projects have made possible the identification of causal links between genotypic & phenotypic changes, and enable the search for hominoid-specific genetic elements controlling tail development.
Here we present evidence that tail-loss evolution was mediated by the insertion of an individual Alu-element into the genome of the hominoid ancestor.
We demonstrate:
this Alu-element (inserted into an intron of the TBXT gene, also called T or Brachyury) pairs with a neighboring ancestral Alu-element encoded in the reverse genomic orientation, and leads to a hominoid-specific alternative splicing event.
To study the effect of this splicing event, we generated a mouse model that mimics the expression of human TBXT products by expressing both full-length & exon-skipped iso-forms of the mouse TBXT ortholog.
We found:
mice with this genotype exhibit the complete absence of a tail or a shortened tail, supporting the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype, albeit with incomplete penetrance.
We further noted:
mice homozygous for the exon-skipped isoforms exhibited embryonic spinal cord malformations, resembling a neural tube defect, which affects ∼1/1000 human neonates.
We propose:
- selection for the loss of the tail along the hominoid lineage was ass.x an adaptive cost of potential neural tube defects,
- this ancient evolutionary trade-off may thus continue to affect human health today.
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‘Jumping gene’ may have erased tails in humans and other apes
— and boosted our risk of birth defects 21.9.21
Adding mobile DNA sequence to developmental gene short-circuits tail development in mice
Mammals from mice to monkeys have tails, but humans & great apes lack them. Now, researchers may have unearthed a simple genetic change that led to our abbreviated back end: an itinerant piece of DNA that leapt into a new chromosomal home, and changed how great apes make a key developmental protein.
The finding also suggests the genetic shift came with a less visible & more dangerous effect: a higher risk of birth defects, involving the developing spinal cord.
Hopi Hoekstra (evol.biol.Harvard Univ.):
The work not only addresses an “inherently interesting question about what makes us human, but also provides new insights into how such evolutionary changes can occur. It’s beautiful work.”
Bo Xia (grad.student genome evolution NYU Grossman Sch.Medicine) wondered as a child why people didn’t have tails,
a tail-bone injury a few years ago renewed his curiosity.
A wealth of primate genomes has been sequenced in recent years, so he started to search for any ape-specific changes in genes known to play a role in tail development.
In a gene called TBXT, he found a strong suspect, a short DNA-insertion called an Alu element, present in all great apes, but missing in other primates.
Alu-sequences can move around the genome, and are sometimes called jumping genes or transposable elements.
Possibly remnants of ancient viruses, they’re common in the human genome, making up c 10 % of our DNA.
Sometimes an Alu-insertion interrupts a gene, and prevents its protein production,
in other cases, the elements have more complex effects, changing where or how a protein is expressed.
Pascal Gagneux (evol.biol.Univ.Calif. San Diego):
This makes them a huge driver of evolutionary variation.
An insertion is “often costly, but every once in a while you hit the jackpot, and a beneficial change arises that evolution preserves.
TBXT codes for a protein called "brachyury": Greek for “short tail” because mutations in it can lead to mice with shorter tails. At first glance, the ape-specific Alu element did not seem to cause any significant disruption in the gene, but on closer inspection, Xia noticed a 2nd Alu-element lurking nearby. That element is present in monkeys & apes, but Xia realized that in apes the 2 Alus could stick together, forming a loop that would alter TBXT expression, so the resulting protein would be a bit shorter than the original.
Hoekstra:
That insight “was very clever, it wouldn’t have jumped out at me as an obvious mutation to test.”
Indeed, Xia cs found that human embryonic stem-cells make 2 versions of the TBXT mRNA, one longer, one shorter.
Mouse cells OTOH only produce the longer transcript.
The researchers then used the genome editor CRISPR to remove one or the other Alu-element in human embryonic stem cells.
Losing either Alu-element made the shorter version of the mRNA disappear.
In other experiments to assess how the abbreviated ape-specific protein might influence tail development, Xia cs used CRISPR to make mice with a shortened version of TBXT.
The mice carrying both copies of the shortened gene didn’t survive, but those with 1 long & 1 short version were born with a variety of tail lengths: from none at all, to nearly normal, the group reports in a preprint posted last week on bioRxiv.
https://www.biorxiv.org/content/10.1101/2021.09.14.460388v1
That suggests to Xia cs that the shorter version of TBXT interferes with tail development.
Because the genetically altered mice had a mix of tail lengths, other genes must be working together to eliminate all tail development in apes & humans, but the ape-specific Alu insertion Xia noticed “was likely a critical event” c 25 Ma as great apes diverged from other simians, says Itai Yanai (developme.geneticist NYU Langone Health, who helped coordinate the project).
The genetically modified mice also had unusu.high levels of neural tube problems, defects in the developing spinal cord.
Such birth defects (which produce spina bifida where the spinal cord doesn’t close, and anencephaly where parts of the brain & skull are missing) are fairly common in humans, affecting c 1 in 1000 newborns.
Yanai:
“We apparently paid a cost for the loss of the tail, and we still feel the echoes. We must have had a clear benefit for losing the tail, whether it was improved locomotion, or something else.”
Hoekstra:
That’s possible, but the defects seen in the mice could well have a different source than the human disorders.
Gagneux:
Overall, the Alu find is “a super interesting story”:
it leads to a wealth of questions, incl. how the shortened protein might help cause neural tube defects.
Some people are born with rudimentary tails, and sequencing their genomes might provide additional clues.
10.1126/science.acx9153