SPRING 2022 | THE SCIENTIST 51ured out that these bits of DNA coopt a cell’s machinery, and the
parasite framing emerged. Further, research showing that TEs
don’t code for essential cellular proteins meant that, at best, they
got lumped in with other kinds of noncoding DNA as genetic junk.
Of course, lots of noncoding DNA has come out of the
“junk” drawer as genomicists have come to realize its various
roles in promoting or suppressing gene expression, for exam-
ple. But until very recently, TEs have broadly been considered
bad for the genome, and pockets of both the popular press
and the scientific literature continue to portray them that way.
This is in part because transposons remain somewhat myste-
rious; the sequencing tools that allowed genomics to blossom
simply aren’t great for sequencing and mapping transposons,
says Chuong. High-throughput methods involve sequencing
genomic segments of only a few hundred base pairs at most—
too short to accurately annotate TEs due to their repetitive
nature, both within their own sequence and in terms of the
many full copies that can exist in each genome. For these rea-
sons, many reference genomes are actually incomplete when it
comes to mapping their TEs: even the human genome wasn’t
completed until 2021.
But with long-read sequencing methods enabling scientists to
document the transposon content—the “mobilome”—of individ-ual organisms, TEs are entering the spotlight. And, it turns out,
they can and do regulate genes. McClintock was right.
In addition to examples such as the peppered moths, work
on fruit flies has demonstrated that TEs can be responsible
for remarkable adaptations. Josefa González Pérez, a genomi-
cist with Pompeu Fabra University (UPF) in Barcelona who
focuses on the genomics of adaptation, has spent much of
her career examining the roles that TEs play in the genomes
of Drosophila. Overall, she says, the evidence is clear that
TEs have been “an integral part of the genome from the very
beginning of evolution.”
In flies specifically, TEs are emerging as key regulators of
Drosophila gene expression. Last year, González Pérez and her
colleagues published work showing that TEs inserted in proxim-
ity to immune genes have a marked influence on the expression
of those genes, even though their insertion occurred relatively
recently in the flies’ evolutionary history. And in at least one
case—a 1-kilobase TE that inserted itself just upstream of a
gene called Bin1—that expression change affects flies’ ability
to survive bacterial infection: when the team knocked out the
TE with CRISPR, the flies succumbed more readily to Pseudo-
monas infection, a fate similar to that of flies that never had
the TE in that genomic location.^3
To look for such variations, known as transposable ele-
ment insertion polymorphisms (TIPs)—places where transpo-
sons had inserted in some genomes, but not others—Mirouze
and her colleagues developed special software called TRACK-
POSON. They have used the program to scan the genomes of
3,000 rice (Oryza sativa) varieties and discovered a stagger-
ing 50,000 TIPs, most of which appeared in only one or two
of the thousands of varieties of the staple crop plant tested.^4
It was a wealth of unseen variation to uncover in one of the
best-studied plant species, says Mirouze. “This tells you that
there’s a lot of diversity that is difficult to capture if you don’t
specifically look for it.”
Another surprising example of TE-based diversity, notes Ludwig-
Maximilians-Universität München geneticist Arne Weiberg,
exists in the mold Botrytis cinerea. According to research by Wei-
berg and his colleagues, this fungus has weaponized its TEs in the
arms race against its plant hosts, allowing it to infect more than
1,400 different plant species.
Weiberg says that the fungus’s generalist strategy intrigued
him. Researchers learned back in 2013 that when B. cinerea
invades a new host, it releases small RNAs that alter plant gene
expression. “They basically fit perfectly into the [RNA interfer-
ence] pathways that the plant has on board,” he says. The evolu-
tion of such RNAs, dubbed virulence factors, through a coevolu-
tionary arms race would seem straightforward in a host-specific
plant, but how B. cinerea was so wildly successful across plant
species wasn’t immediately obvious to Weiberg.
Work from other researchers had shown that the fungus eases
up on transposon silencing during infection, and that this “waking
up” of sleeping transposons results in increased expression of vir-TIPsTIPs
When scientists want to probe the genetic basis of adap-
tation, they usually turn to single nucleotide polymor-
phisms (SNPs). These exist in transposons, but these mobile
genetic elements also vary in their location. Transposable
element insertion polymorphisms (TIPs) are chunks of chro-
mosome where transposons have inserted in some individu-
als but not others, and these can be quite common. A 2019
study of 3,000 rice (Oryza sativa) varieties revealed 50,000
TIPs in their genomes, for example (Nat Commun, 10:24).© JULIA MOORE, WWW.MOOREILLUSTRATIONS.COM