Scientific American - USA (2022-02)

44 Scientific American, February 2022

constantly in every species. But in two studies, Mueller

estimated that salamanders clear out their inserted trans­

posons several times more slowly than zebra fish or

humans. This pace shifts the balance toward transposons

accumulating rather than remaining constant, leaving

the salamander genomes increasingly bloated over time.

That extra DNA has profoundly altered salamanders’

bodies, brains and hearts. In species with the very largest

genomes, the anatomic distortions are obvious at a glance.

EMBRYONIC BRAINS

gigaNTic geNomes often turn salamanders into overgrown

babies. Of the 766 known species, more than 39 have lost

the ability to metamorphose from aquatic larvae into

landlubbing adults. (Another 39 metamorphose only

occasionally.) These species tend to have larger genomes

than others that do metamorphose. Like the Neuse River

waterdog, they spend their entire lives confined to water

with larval gills and weakling limbs.

Many of them are also missing toes because their

limbs never finish developing. The waterdog has only

four toes on its rear feet (most salamanders have five).

Species of amphiuma have three, two or even just one

toe per foot. And species in the siren family, which in ­

habit the southeastern U.S., have no rear legs at all.

Even land­dwelling salamanders with adult­looking

bodies often have babylike traits, such as unfused skull

bones or foot skeletons that haven’t hardened into bone.

A series of discoveries between 1988 and 1997 showed

that many of these species even have larvalike brains.

The revelations began when David Wake, a promi­

nent salamander biologist at the University of Califor­

nia, Berkeley, teamed up with Gerhard Roth, then a

Ph.D. student at the University of Bremen in Germany.

They decided to compare the brain structures of sev­

eral dozen species of frogs and land­dwelling pletho­

dontid salamanders.

Wake removed the critters’ brains and soaked them

in cedar wood oil, which turned them transparent for

viewing under a microscope. As he and Roth examined

the brains, they realized that most had simpler structures

than those of frogs, which are also amphibians and there­

fore close relatives. The salamander nerve cells looked

“embryonic,” according to Wake: larger, rounder and less

differentiated into specialized cell types.

This simplification was especially dramatic in the

visual system. The salamanders had no more than 75,000

neural fibers in their optic nerves (which carry signals

from the eyes to the brain); frogs had up to 470,000

fibers. In salamanders, far fewer of these nerve fibers

were coated with myelin sheaths, which allow signals to

reach the brain more quickly. And in the tectum, a brain

region that processes images from the optic nerve, the

neurons of salamanders were often strewn chaotically

about—a trait seen in embryonic or larval brains—

whereas in frogs, the neurons were nicely layered. Wake

and Roth went on to show that salamanders with larger

genomes generally have simpler visual systems.

In all of this, Roth was struck by one overarching pat­

tern: the features missing in salamander brains were

those that arise late in development. It seemed as if the

critters’ brains had run out of time to finish maturing.

This stipulation made a lot of sense because another sci­

entist had just demonstrated a link between salaman­

ders’ large genomes and their slow development.

Stanley Sessions, a former student of Wake’s (like sev­

eral of the experts in this story), was studying salaman­

ders’ special talent for regenerating severed limbs. Ses­

sions, now a professor emeritus at Hartwick College,

amputated the right rear legs from 27 species of pletho­

dontid salamanders and measured how quickly they

grew back. The animals’ genomes varied from 13 to 74

gigabases (four to 24 times the human genome). Sure

enough, Sessions found that animals with larger genomes

regenerated more slowly. Their immature cells took lon­

ger to differentiate into specialized tissues such as

muscle or bone.

The studies by Wake, Roth and Sessions also provided

a rationale for understanding why salamanders with some

of the largest genomes of all had lost toes, hind legs and

even their ability to undergo metamorphosis. Their hefty

genomes had slowed and truncated many aspects of

development. People assumed that this depressed devel­

opment stemmed from the simple fact that large genomes

take longer to copy, so cells divide more slowly. But in 2018

a new milestone in genomics provided a critical insight.

Researchers published the first complete salamander

ge nome, for the Mexican axolotl. This beast can grow al ­

most as long as a person’s forearm. It has pencil legs,

fluffy gills and other larval traits but has a genome of

“only” 32 gigabases, compared with the waterdog’s 118

gigabases. This study showed that the animal’s transpo­

sons aren’t just scattered among its genes; they are also

abundant within genes, in regions called introns.

This minor detail has enormous implications. When

a gene is turned on, its entire length of DNA, including

introns, must be copied into a chain of RNA. The introns

must then be clipped out before the RNA chain can be

used as a template to make proteins that will guide a cell’s

development. Axolotl introns are up to 13 times longer

than human introns, because they are crowded with

transposons. Therefore, the RNA chains take longer to

build. The instructions for how cells should specialize

take longer to exert their effects—so long, Sessions says,

that salamanders “never quite grow up.”

Slow development is only part of how giant genomes

distort bodies. Massive genomes have another major

impact. Scientists accidentally noticed it more than 150

years ago, but its importance is just now being recognized.

HEARTS LIKE PAPER BAGS

duriNg The early 1800 s a British army surgeon named

George Gulliver pursued a pet interest as he traveled the

world. At each destination he collected blood from local

species, viewed the samples under a microscope and

measured the red blood cells. He surveyed Mexican deer,

American crocodiles, Indian pythons, spiny dogfish, elec­

tric eels, armadillos and hundreds of other animals.