February 2022, ScientificAmerican.com 47entiate into new tissues. “Salamanders are basically
walking bags of stem cells,” he says. This theory, which
he put forth with Wake, was published in June 2021,
shortly after Wake died.
The idea has “some plausibility,” says Jeramiah Smith,
who studies the axolotl genome at the University of Ken
tucky. He cautions that the picture may not be so simple;
life has many ways of slowing down development when
it is advantageous to do so. But with transposons so
abundant in the salamander genome, it makes sense that
they would play a role. “Evolution works with the mate
rial it has,” Smith says.
The theory, if true, could have major repercussions.
Scientists have spent decades studying salamander
regeneration, in hopes of finding ways to regrow human
tissues. But if regeneration requires having a multitude
of genes with long introns, that could make the goal
more challenging.
On a more profound level, Wake and Sessions’s the
ory reflects the great depth to which genetic parasites
have reprogrammed the very biology of salamanders.
Many longlived species such as humans keep their
remaining stem cells muzzled once development is
complete, an evolutionary tradeoff that reduces the
ever present risk of runaway cell division, which can
cause cancer. Salamanders’ stem cells are more numer
ous and far less constrained.
Wake and Sessions’s theory may not fully explain why
salamanders can tolerate huge genomes. Although it is
handy to be able to regrow appendages that are lost on
rare occasions, salamanders still have to survive day after
day with those bizarre distortions of their hearts, brains
and bodies. This paradox points to a surprising possibil
ity, which emerged during a conversation between Muel
ler, Itgen and Hanken in mid2021.
The trio were on a Zoom call, discussing how the hol
lowedout hearts might affect the survival of salaman
ders. “I’ll take the extreme position,” Hanken said. Maybe
the hollow hearts “are not having any impact” at all.
Strange as it might seem, that suggestion made sense
to Mueller and Itgen. Salamanders grow and move slowly.
They have by far the lowest metabolic rates and oxygen
needs of any vertebrates. The plethodontids that Itgen
and Mueller study don’t even have lungs. Maybe sala
manders tolerate hollow ventricles, Itgen said, “because
the functional requirements on the heart are so low.”
Indeed, when Sessions ran his regeneration experi
ments, he also removed up to half of the lone ventricle
in a dozen eastern newts. The blood gushed out, and the
hearts stopped beating, yet the animals survived and
grew new ventricles—suggesting that they may not need
their hearts as much as mammals do.
Salamanders don’t seem to pay a price for their odd
skeletons, either. Hanken thinks Thorius tolerates slip
shod wrist bones because the animals’ bodies are so small
that the forces on their joints are minuscule. And Tho-
rius doesn’t need the finetuned limbs of a cheetah,
because it doesn’t chase its prey. It simply sits and waits
for an insect to happen by.
Roth adds that if salamanders are just waiting for
prey, they can simplify their entire vision system. The
most extreme examples are the bolitoglossine salaman
ders of Europe and the Americas. These species include
the largest genomes of any landdwelling animals, up
to 83 gigabases (24 times the human genome). They also
happen to have the most strippeddown brains that
Roth and Wake have ever seen in a salamander. They
have lost 50 to 90 percent of their visual neurons to sim
plification, leaving them unable to distinguish between
an insect crawling past them and a shiny metal pellet
rolling by. What bolitoglossines do have, however, is one
of the fastest tongues on Earth—“like walking around
with a cocked gun,” Wake said—able to zap an insect
within a few milliseconds.
If you have that kind of tongue, if you don’t need to
see very well, if you can sit still for long periods, all that
takes a lot of pressure off the body. You can have a sim
plified brain, a hollow heart and weird wrist bones, “and
it doesn’t matter,” Mueller says. “It’s pretty profound.”CRUEL IRONY
ever siNce iT became clear that salamanders and lung
fish have far more DNA than humans, scientists have
debated what purpose this extra DNA might serve. Ini
tially some of them argued that DNA, in addition to its
informational content, serves as a scaffold that deter
mines the size of a cell’s nucleus. That idea has fallen by
the wayside. The latest view is more nuanced.
Transposons are indeed junk DNA, says Ting Wang,
a genomic scientist who studies transposons at the Wash
ington University School of Medicine in St. Louis. But
this junk, scattered across the genome, becomes fodder
for evolution. Sometimes it takes on legitimate functions.
Transposons that land close to a gene can cause the gene
to turn on more strongly, for example. In 2021 Wang dis
covered a transposon that activates a critical gene in
mouse embryos; delete that single transposon, and many
of the embryos die. Transposons also play structural roles,
partitioning our genome into functional sections. “You
can’t separate them from us anymore,” Wang says.
“They’re part of us.”
And yet they can betray us. When Wang’s team ana
lyzed nearly 8,000 human tumors in 2019, the research
ers found that in half, transposons were turning on key
oncogenes that were driving the cancer’s explosive growth.
All of this suggests that although transposons are
sometimes coopted by the host, they have no inherent
purpose. “Not everything is adaptive,” says T. Ryan Greg
ory, a biologist who studies genome size at the Univer
sity of Guelph in Ontario. DNA exists for its own sake. It
doesn’t just evolve to maximize the survival of its host;
it also evolves to maximize itself—the host be damned.
As the host struggles to maintain its niche in the
world, an equally dramatic struggle plays out in its cells.
Transposons compete to populate the genomic landscape
and evade predation by cell defenses. “We’re starting to
think about the genome as an ecological community and
the transposable elements as species,” Mueller says.