New study finds evolutionary novelty may be due to rearrangement of preexisting genes by transposons

If and how new protein architectures evolved from preexisting ones has been a leading question in biology for nearly two centuries. Now new research points to the role of transposons, repetitive DNA sequences that move from one location to another within the genome, in rearranging preexisting genetic information to create fundamental changes in the genetic code. 

The study surveyed 596 species of tetrapods––the four-limbed animals that include reptiles, amphibians, mammals, and marsupials––for chimeric genes that are a fusion between a host gene and a transposon. They identified 94 distinct cases of fusion events over the last 300 million years of evolutionary history.

This path-breaking work was described in a research article in the journal Science in February. 

Authors of the new study are Rachel Cosby, Julius Judd, Ruiling Zhang, Allen Zhong, Nathaniel Garry, and Ellen Pritham, all of the Department of Molecular Biology and Genetics, Cornell University, and Cédric Feschotte of the Department of Human Genetics, University of Utah School of Medicine. 

Prior to this, the role of exon shuffling, the rearrangement of pre-existing protein-coding domains, had been studied as one mechanism for the evolution of new protein architectures (exons are the part of the DNA responsible for coding proteins). 

The new work looks at the details of how new exons might form in the process of exon shuffling. “Although exon shuffling is thought to account for the evolution of many protein structures, the source of new exons and splice sites as well as the mechanisms by which they become assimilated have been scarcely characterized,” the authors write. 

Transposons

Transposons, also known as transposable elements or “jumping genes,” are widespread in the eukaryote kingdom, making up 44% of the human genome, and a higher percentage in some plants and other animals. Historically, they have been considered parasites. In order to reproduce they must exploit the transcription and translation apparatus of the host cell. 

Different forms of parasitic mobile elements exist in prokaryotic and virus cells, the whole complex being labeled as the mobilome. 

The transposon reproduces by inserting a copy of its genome into the host genome. The combining of the transposon with the host genome is known as a fusion event. Once integrated into the host DNA, the transposon moves into different genomic locations. This can create exon shuffling which may produce new gene combinations and functions.

The new study finds that such events are relatively common and widespread across the animal kingdom. 

“Our findings confirm that exon shuffling is a major evolutionary force generating genetic novelty,” the authors write. “We provide evidence that DNA transposons promote exon shuffling by inserting transposase domains in new genomic contexts. This process provides a plausible path for the emergence of several ancient transcription factors with important developmental functions. 

“By illustrating how a transcription factor and its dispersed binding sites can emerge simultaneously from a single transposon family, our results bolster the view that transposons are key players in the evolution of gene regulatory networks,” they conclude. 

Legacy of Barbara McClintock

The existence of transposable elements within the chromosome dates back to the work of Barbara McClintock in the 1940s, carried out at Cornell University where five of the six authors of the present study did their work. 

McClintock’s 1948 discovery of the existence of transposable elements (then called “mobile genetic elements”) in the chromosome of maize plants was largely ignored for several decades before recognition finally led to the award of a Nobel Prize in Medicine in 1983.

The work in context

A perspective review of the work of Cosby, et al. appears in the same February 2021 issue of Science magazine, written by two specialists from the University of Pittsburgh School of Medicine. 

Aaron Wacholder and Anne-Ruxandra Carvunis describe the new work of Cosby, et al. as an expansion and generalization of “previous work that has characterized a small sample of host-transposon fusion proteins.”

“By using large-scale genomic comparison, Cosby et al. were able to reconstruct the general process by which DNA transposon domains are captured by host genes," they write. "Some DNA transposon families have been highly successful at replicating within tetrapod genomes, inserting themselves in proximity with numerous host genes.”

“The fusion product emerges initially as an alternative splice isoform to the main prefusion product and then becomes the dominant isoform through DNA sequence changes over evolutionary time,” Wacholder and Carvunis argue. 

Discussing the other mechanisms by which evolutionary change of the genome may occur, they note: “A major open question is the relative contributions of these mechanisms [duplication and divergence, gene rearrangement, de novo birth, and extreme divergence] to gene formation and functional innovation.” 

“Perhaps even more important will be to determine the distinct contexts in which these mechanisms contribute to innovation and how the mechanism of origin affects the type of molecular, physiological, and evolutionary impacts the newly created genes can have,” they conclude.

–––––––––––

Rachel L. Cosby, et al. Recurrent evolution of vertebrate transcription factors by transposase capture. Science (2021). DOI: https://doi.org/10.1126/science.abc6405

Wacholder & Carvunis. New Genes from borrowed parts. Science (2021). DOI: https://doi.org/10.1126/science.abf8493