News | Cornell team uses next-generation sequencing to reveal how transposons move and reshape the genome
Cornell University researchers report that CUT&Tag, a high-resolution genome-mapping method originally used to study chromatin, can overcome the bias of conventional sequencing against repetitive sequences. It provides unprecedented clarity on how transposons move, locate and function within the genome. Once dismissed as "junk DNA," these genetic elements are now recognized as important participants in immune responses, neurological function, embryo development and evolution.
The study was published in iScience on November 21. Corresponding author Patrick Murphy (Ph.D. ’13), associate professor of molecular biology and genetics in Cornell's College of Agriculture and Life Sciences, said the advance accurately captures solid genomic material previously discarded during sample preparation, where transposons are concentrated.
"Junk DNA" is not junk, but ancient viral remnants deeply involved in biological function
Transposons were first discovered in corn by Nobel laureate Barbara McClintock. They originated from ancient viral infections. When viral DNA entered the host's germ cells, it could be inherited across generations and gradually incorporated into the genome. "These ancient viral DNA sequences are no longer inactive remnants; they have become key components that help us function," Murphy said.
In humans, transposon "jumping" can cause mutations that may contribute to disease, including hemophilia and some cancers, or protect against modern infections. Certain transposons are activated at the earliest stages of embryo development and have key roles in stem-cell formation and placental development, helping drive mammalian evolution.
Although transposons make up half of the human genome, much about their function remains unknown. Conventional sequencing lyses cells and separates solid and liquid phases. For decades researchers mainly studied DNA in the liquid phase, while the transposon-rich solid fraction was overlooked because suitable methods were unavailable, contributing to the "junk DNA" label.
"We found that the discarded solid fraction is actually where most transposons are located," Murphy said.
CUT&Tag gives a voice to the overlooked half of the genome
CUT&Tag was introduced in 2019 to study chromatin structure. The Cornell team showed that it also works in transposon regions rich in repetitive sequences and complex structures while avoiding biases associated with conventional methods such as ChIP. The advance has broad interdisciplinary potential.
Some cancer-treatment strategies activate transposons in the genome to trigger immune attacks on tumor cells. Better understanding of these mechanisms could support more precise targeted therapies. "Over the next five to ten years, we will enter a golden age of transposon research, with broad potential impact on clinical treatment, fertility medicine, developmental research, agricultural breeding, microbiology and speciation," Murphy predicted.
Cross-institutional collaboration advances the research
First author Brandon Park joined Murphy's laboratory when Murphy was a professor at the University of Rochester. Other authors included Cornell College of Veterinary Medicine senior researcher Kristin Murphy (Ph.D. ’13), postdoctoral researcher Shan Hua, researcher Karli Casler and collaborators from Mitchell O’Connell's laboratory at the University of Rochester. The study was funded by the National Institutes of Health (NIH).
News | Cornell team uses next-generation sequencing to reveal how transposons move and reshape the genome
News | Cornell team uses next-generation sequencing to reveal how transposons move and reshape the genome
Cornell University researchers report that CUT&Tag, a high-resolution genome-mapping method originally used to study chromatin, can overcome the bias of conventional sequencing against repetitive sequences. It provides unprecedented clarity on how transposons move, locate and function within the genome. Once dismissed as "junk DNA," these genetic elements are now recognized as important participants in immune responses, neurological function, embryo development and evolution.
The study was published in iScience on November 21. Corresponding author Patrick Murphy (Ph.D. ’13), associate professor of molecular biology and genetics in Cornell's College of Agriculture and Life Sciences, said the advance accurately captures solid genomic material previously discarded during sample preparation, where transposons are concentrated.
"Junk DNA" is not junk, but ancient viral remnants deeply involved in biological function
Transposons were first discovered in corn by Nobel laureate Barbara McClintock. They originated from ancient viral infections. When viral DNA entered the host's germ cells, it could be inherited across generations and gradually incorporated into the genome. "These ancient viral DNA sequences are no longer inactive remnants; they have become key components that help us function," Murphy said.
In humans, transposon "jumping" can cause mutations that may contribute to disease, including hemophilia and some cancers, or protect against modern infections. Certain transposons are activated at the earliest stages of embryo development and have key roles in stem-cell formation and placental development, helping drive mammalian evolution.
Although transposons make up half of the human genome, much about their function remains unknown. Conventional sequencing lyses cells and separates solid and liquid phases. For decades researchers mainly studied DNA in the liquid phase, while the transposon-rich solid fraction was overlooked because suitable methods were unavailable, contributing to the "junk DNA" label.
"We found that the discarded solid fraction is actually where most transposons are located," Murphy said.
CUT&Tag gives a voice to the overlooked half of the genome
CUT&Tag was introduced in 2019 to study chromatin structure. The Cornell team showed that it also works in transposon regions rich in repetitive sequences and complex structures while avoiding biases associated with conventional methods such as ChIP. The advance has broad interdisciplinary potential.
Some cancer-treatment strategies activate transposons in the genome to trigger immune attacks on tumor cells. Better understanding of these mechanisms could support more precise targeted therapies. "Over the next five to ten years, we will enter a golden age of transposon research, with broad potential impact on clinical treatment, fertility medicine, developmental research, agricultural breeding, microbiology and speciation," Murphy predicted.
Cross-institutional collaboration advances the research
First author Brandon Park joined Murphy's laboratory when Murphy was a professor at the University of Rochester. Other authors included Cornell College of Veterinary Medicine senior researcher Kristin Murphy (Ph.D. ’13), postdoctoral researcher Shan Hua, researcher Karli Casler and collaborators from Mitchell O’Connell's laboratory at the University of Rochester. The study was funded by the National Institutes of Health (NIH).
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