Multiple divergent retrocopies of the well-characterized Ku70 gene were identified in humans and other primates.
The last 63 million years of primate evolution have been strongly shaped by genetic retrotransposition; thousands of genes and proteins with new functions have evolved from retrocopies scattered throughout the genome. These retrocopies arise when retrotransposons reverse transcribe a cellular mRNA and insert the resulting cDNA copy back into the genome.
A recent study published in G3: Genes|Genomes|Genetics characterized a new family of five retrocopies in the human genome. These retrocopies—which researchers named NUKUs—are derived from KU70, a highly conserved gene that encodes a ubiquitous protein involved in DNA double-strand break repair.
“Many people think retrocopies are junk DNA, but there are many examples where they have functional relevance in humans and other organisms,” says lead author Paul Rowley of the University of Idaho. Rowley and his collaborators found that NUKUs are among those retrocopies that may have a function that differs from that of the original parent gene.
The long journey to identifying and characterizing NUKUs
More than 10 years ago, scientists studying Ku70 performed a BLAST search for the gene in the human genome. They noticed that additional genes came up in the search results, often truncated or missing introns.
“It raised some eyebrows, because very few other genes in the DNA double-strand break repair pathway have this many retrocopies,” says Rowley. Since that initial observation, numerous scientists have contributed to the ongoing process of characterizing these NUKU retrocopies.
Through experiments, the researchers demonstrated that NUKUs are transcribed in human tissue. To determine whether these retrogene transcripts were capable of producing proteins, they mined existing Ribo-seq (ribosome profiling) datasets to look for unique NUKU transcripts that were easily distinguishable from Ku70 and other transcripts.
“The day when we confirmed the ribosome association of the transcripts—that was a good day,” says Rowley. “We had already spent a lot of time showing that NUKUs are transcribed, but without ribosome association, any case for full protein translation is pretty much dead in the water.”
Rowley emphasizes the collaborative nature of this work. “Being supported through the Institute for Modeling Collaboration and Innovation enabled me as an empiricist to bring expertise in molecular and computational modeling on board, which really strengthened the paper and laid better groundwork for future studies,” he says.
Hypothesizing functionality
The researchers have not yet determined the functionality of NUKU genes, but they know enough to conclude that they aren’t exact functional duplicates of Ku70.
“You would imagine that a retrocopy would function as a bona fide copy of its parental gene, but if these proteins are doing something in the cell, they certainly seem to have lost their canonical function through truncation and specific mutations,” says Rowley.
The Ku70p protein interacts with Ku80p, the other half of the eukaryotic Ku heterodimer. Through computational modeling, collaborator Jagdish Patel demonstrated that the mutations in the NUKU retrogenes would disrupt the NUKU proteins’ ability to bind Ku80p. Without the ability to form a heterodimer, it is unlikely that NUKUs are involved in DNA double-strand break repair. Their expression patterns suggest divergence too: while Ku70 is expressed fairly ubiquitously, NUKU transcripts show greater tissue specificity. Together, the study’s results suggest that NUKUs evolved rapidly during primate speciation and that the genes developed novel functions separate from Ku70.
Future studies will aim to identify possible functions of this familiar-yet-distinct gene family. These studies might also provide broader evolutionary insights by revealing factors driving the selection of specific mutations in NUKUs, such as regulation or interactions with pathogens or other host proteins.
CITATION
NUKU, a family of primate retrocopies derived from KU70
Paul A Rowley, Aisha Ellahi, Kyudong Han, Jagdish Suresh Patel, James T Van Leuven, Sara L Sawyer
G3 Genes|Genomes|Genetics 2021; jkab163
Grace Niewijk is a freelance science writer and editor from Chicago. Her writing has appeared in Genetic Engineering & Biotechnology News, Clinical OMICs, Proto Magazine, and elsewhere. She holds a degree in molecular biophysics and biochemistry from Yale.
View all posts by Grace Niewijk »Read more in
-
In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation
Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…
-
Congratulations to the #Fungal24 Poster Award winners!
We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…
-
Poster presentation tips for TAGC 2024
You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…
-
Maximize your TAGC 2024 experience
A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…
-
Early Career Leadership Spotlight: Sarah Petrosky
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…
-
TAGC 2024 Early Career Award Winners
GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024. Don’t miss the opportunity…
-
Preeminent geneticists recognized with revamped GSA Awards
In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…
-
Fly Board funds outreach programs to spread the word about Drosophila research
In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…
-
New members of the GSA Board of Directors: 2024–2026
We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…
-
Parrot plumage study aids breeders and endangered natural populations
Yellow coloration is maladaptive in the wild but prized by breeders. People have long been fascinated with birds, which exhibit one of the widest ranges of coloration among vertebrates. Parrots, in particular, have captivated humans by their ability to mimic human speech and spectacular plumage. Brightly colored feathers are used primarily to attract mates, intimidate…
-
Early Career Leadership Spotlight: Sarah Gilmour
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah GilmourMultimedia SubcommitteeStowers Institute for Medical Research Research Interest Questions of evolution have always fascinated me. I am extremely fortunate to be starting out my research career in a…