Scientists discover protein factories hidden in human jumping genes

Salk scientists discover protein factories hidden in human jumping genes
Salk researchers discovered a new genetic component, called ORF0, spread throughout the DNA of humans, chimps and most other primates. This image shows the locations of the ORFO on human and chimp chromosomes. Credit: Salk Institute

Scientists have discovered a previously unknown wellspring of genetic diversity in humans, chimps and most other primates. This diversity arises from a new component of itinerant sections of genetic code known as jumping genes.

In a paper published October 22, 2015 in Cell, Salk scientists report finding human and chimp DNA peppered with sequences of genetic code they've dubbed ORF0, which spreads throughout the genome on jumping . The ORF0 sequences may produce hundreds or even thousands of previously unknown proteins.

The abundance of ORF0 instances in the suggests that it played—and still plays—an important role in evolutionary diversity and flexibility by serving as a mechanism for generating novel proteins. The discovery of these mobile protein factories may also shine light on the origins of genetic mutations responsible for cancer, mental disorders and other diseases.

"This discovery shows that jumping genes are an even more important source of variation in the primate genome than we thought, whether you're looking at the level of different species, different people or even the different cells within an individual's body," says Rusty Gage, senior author of the paper and a professor in Salk's Laboratory of Genetics.

With the sequencing of the human genome, it became clear that jumping genes—mobile genetic elements first discovered in maize by Barbara McClintock in the early 1950s—were also present and highly active during human evolution. About half of the human genome resulted from sequences of that moved or insert extra copies of themselves throughout the genome.

The evolutionary importance of jumping genes was highlighted by the results of another recent study by Gage and collaborators at Stanford. The research used stem cell technologies developed in Gage's lab to explore how differences in gene expression contribute to human and chimp facial structure. The findings, also reported in Cell, suggested that jumping genes played a role in the evolutionary split between humans and other primates.

In the more recent study that uncovered ORF0, Gage and his colleagues focused on a class of jumping genes known as LINE-1 elements, which make up about 17 percent of the human genome. These elements contain all the necessary genetic machinery for moving themselves and other classes of jumping genes, unaided, to elsewhere in the genome.

Previously, it was thought that LINE-1 elements contain just two sequences that coded for proteins, the ultimate product of genes that serve a wide range of roles in our cells and organs. These sequences are known as open reading frames (ORF), and the two previously known sequences, ORF1 and ORF2, are thought to be involved in producing proteins that are important for allowing LINE-1 elements to move around in the genome.

In their new study, Gage and his colleagues discovered a third open reading frame. They named it ORF0 based on its location in the LINE-1 element next to ORF1. The scientists found ORF0 in about 3,500 locations in the DNA of humans and about 3,000 locations in the chimp and most other primate genomes.

The structure of LINE-1 elements is such that when an element moves to another site there is a possibility that the ORF0 sequence can blend with genetic sequences in new location in DNA. The result of the new gene sequences can be a new protein. Evolutionarily speaking, this represents a way to generate entirely new molecules that could be beneficial to a species. On the other hand, the reshuffling of an existing ORF0 sequence during a jump could result in a disease-causing mutation.

"This discovery redraws the blueprint of an important piece of genetic machinery in primates, adding a completely new gear," says Ahmet Denli, a staff scientist in Gage's lab and the first author on the paper reporting the findings. "Jumping genes with ORF0 are basically protein factories with wheels, and over the eons evolution has been driving the bus."

Now that they have identified ORF0 in the primate genome, Denli says they plan to determine how many of the instances of ORF0 actually code for proteins and to investigate what function those proteins serve.

The researchers also plan to investigate the behavior of ORF0 in different cell types and diseases. They are particularly interested in exploring its role in cancers and in neurological disorders such as schizophrenia, where previous studies have suggested may be involved.

Explore further

'Jumping genes' may drive esophageal cancer

Journal information: Cell

Provided by Salk Institute
Citation: Scientists discover protein factories hidden in human jumping genes (2015, October 22) retrieved 17 June 2019 from
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Feedback to editors

User comments

Oct 22, 2015
See also: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Conclusion: "...the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific 'fit'."

See also: Speedy evolution affects more than one species

Everything currently known seems to be linked to nutrient-dependent RNA-mediated retrotransposon-mediated biodiversity.

Oct 22, 2015
Nutrient-dependent/pheromone-controlled adaptive evolution: a model
a DEBUNKED model, as prove here: http://www.socioa...ew/24367

in fact, it was also admonished by the senior staff as well. Everyone can read that here:

Based on his writings, both published and unpublished, James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others' research. It was a mistake to let such a sloppy review through to be published.
most accurate description yet, combined with the one here:

so quit posting pseudoscience!

Oct 23, 2015
The "protein factories" are nutrient-dependent and linked to the physiology of reproduction by RNA-mediated gene duplication and RNA-mediated amino acid substitutions that differentiate the cell types of all living genera.

That's why I provided examples of biologically-based cause and effect in my model. There is no other model, which means my model has not been debunked. Instead it has been supported by everything reported that has since continued to link physics and chemistry to biophysically constrained RNA-mediated protein folding in all living genera.

The fact that viruses perturb RNA-mediated protein folding links them to all pathology. Nutrient-dependent RNA-mediated DNA repair is linked to healthy longevity in the context of what is known about an atoms to ecosystems model, which is well portrayed in this parody. All About that Base (Meghan Trainor Parody)

Oct 24, 2015

That's why I provided examples of biologically-based cause and effect in my model. There is no other model, which means my model has not been debunked.

JVK's model debunked:

Oct 24, 2015
Everything currently known seems to be linked to nutrient-dependent RNA-mediated retrotransposon-mediated biodiversity.

I'm growing a vagina...
Is it something I ate?

Oct 24, 2015
Please consider learning something about base pairs and the nutrient-dependent biophysically constrained RNA-mediated protein folding that links microbes to humans rather than continue your displays of ignorance.

See also: The power of two may help explain brain design http://medicalxpr...ain.html

Chemists Know - (Parody of "Let It Go" from Frozen) - University of California Irvine

Oct 24, 2015
There is no other model
!- the Theory of Evolution
2- it contains models that are based upon repeatable experimentation, like Lenski and Extavour: those studies are called VALIDATED... your model is called CONJECTURE
my model has not been debunked
This is partially true... to use correct scientific jargon/terminology, it has been FALSIFIED, because you are not correct or factual in your information and misleading in your techno-babble. this is demonstrated in the following link: http://www.ncbi.n...4049134/

however, given that your model is falsified because you are fallacious in your assumptions (means you lie or you are ignorant of biology) and you are not fully encompassing or able to refute Evolution as you claim, that means, technically, your model IS debunked (in layman terms)

perhaps you should pay some real mensa members to come translate for you?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more