Bo Xia, a graduate student at New York University’s (NYU)
Grossman School of Medicine, wondered why humans don’t have tails like some
other primates. Many primate genomes have been sequenced over recent years, so
Xia began to look at genes associated with tail growth and noticed an Alu
element present on the TBXT gene of all primates. The TBXT gene codes for a
protein called brachyury and is known to be related to tail development. For
starters, what is an Alu element? Alu elements are sequences of repetitive DNA
material that are inserted into the genome and have been known to “move around”,
earning them the name “jumping genes” or transposable elements. These are
common sequences in the human genome and actually make up about 10% of our DNA,
however when they do jump around on the genome, they can interrupt certain
genes or gene regulatory sequences leading to defective proteins or improper
gene regulation. As we study evolution, it is noted that sometimes these Alu
elements result in advantageous adaptations in the organism that are passed to
future generations.
Looking back at the apes, at first appearance this Alu
element, noted by Xia, on the TBXT gene did not appear to cause any major disruptions,
however when Xia looked closer, there appeared to be a second Alu element
nearby on the TBXT gene in great apes that stuck to the first Alu element resulting
in a loop and therefore a shortened brachyury protein.
This was further confirmed in mice. Using CRISPR technology,
a shortened TBXT gene was inserted in the genome of mice. The offspring that
were heterozygous for the shortened TBXT gene were noted to have shortened
tails, though with varying lengths. This indicates there are likely other genes
involved in the determination of tail length, however this TBXT Alu element
addition was likely a critical event. What was not expected from these experiments,
was that many of the mice offspring that were homozygous for the mutation, experienced
neural tube defects of the developing spinal cord resulting in disorders like anencephaly
and spina bifida. It is discussed that even though this mutation in the TBXT
gene was likely a very important event leading to the tail being eliminated in
apes and humans, this may have come at the cost of an increased incidence of neural
tube defects.
Though this paper and its implications are awaiting peer
review, it still brings forth a potentially fascinating discovery in the evolution
of human beings and what these advantages may have cost. Spina bifida occurs in
approximately 1 in 1000 newborns worldwide, indicating this Alu element must
have been so advantageous in the evolution of apes and humans, that it was outweighed
the risk of these spinal cord disorders. The possible identification of a
contributing factor to these disorders can provide a great starting point for
future research into the treatment and prevention of spina bifida or even
anencephaly.
Vogel, G. (2021,
September 21). ‘Jumping gene’ may have erased tails in humans and other apes
– and boosted our risk of birth defects. Science. https://www.science.org/content/article/jumping-gene-may-have-erased-tails-humans-and-other-apes-and-boosted-our-risk-birth-defects
Xia, B., Zhang,
W., Wudzinska, A., Huang, E., Brosh, R., Pour, M., Miller, A., Dasen, J.,
Maurano, M., Kim, S., Boeke, J., & Yanai, I. (2021). The genetic basis of
tail-loss evolution in humans and apes. BioRxiv The Preprint Server for
Biology. https://doi.org/10.1101/2021.09.14.460388
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