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Biological Chemistry

Creating hybrid plant and human cells yields evolutionary insights

Fusing plant and human cells in the lab gives scientists a way to study the evolution of chromosome function

by Melissa Pandika
December 7, 2016

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Credit: ACS Synth. Biol.
Human bone cancer cells (purple) fused with Arabidopsis thaliana cells (green) create hybrid human-plant chromosomes that replicate inside a human cell. Over generations of cultivation, plant-only chromosomes that express hundreds of Arabidopsis genes (bottom) emerge alongside human-only chromosomes.
Schematic of formation of plant-human hybrid cells.
Credit: ACS Synth. Biol.
Human bone cancer cells (purple) fused with Arabidopsis thaliana cells (green) create hybrid human-plant chromosomes that replicate inside a human cell. Over generations of cultivation, plant-only chromosomes that express hundreds of Arabidopsis genes (bottom) emerge alongside human-only chromosomes.

Human chromosomes behave in much the same way as those of rodents, primates, and other close evolutionary cousins. But researchers don’t know whether those similarities might extend to distantly related organisms, such as plants. Now, researchers have created plant-human hybrid cells that could help reveal the extent to which evolution has conserved chromosome functions across the plant and animal kingdoms (ACS Synth. Biol. 2016, DOI: 10.1021/acssynbio.6b00180).

Fusing the cells resulted in plant chromosomes housed in a human cell, indicating that plant chromosomes can function by using human cellular machinery. Scientists fused human cervical cancer cells with tobacco cells in 1976, but the hybrids didn’t remain viable beyond six days. Later attempts at plant-human hybrids in the 1970s and 80s failed. In the current study, researchers led by Mitsuo Oshimura of Tottori University fused cells from Arabidopsis thaliana—a small flowering plant used as a model organism in genetic studies—with human bone cancer cells.

Oshimura and colleagues first introduced genes for enhanced green fluorescent protein (EGFP) and a protein that confers resistance to the antibiotic blasticidin into Arabidopsis cells. The researchers then combined the isolated plant cells with human bone cancer cells, allowed them to fuse, and then exposed the hybrids to blasticidin. The cells that were not killed by the antibiotic and also glowed green indicated that genes introduced with the plant DNA were being expressed by the human cells.

Next, they analyzed the chromosomes in these hybrid cells with fluorescent probes. They found evidence of DNA fragments from both types of cells on at least one chromosome, meaning that the chromosomes had fused together. The researchers found that most of the plant DNA in the hybrid cells came from three of the plant’s 10 chromosomes, indicating a partial, but not complete, hybridization of their genomes. After around 60 days, representing multiple generations of cells, the researchers noticed that these fused chromosomes were gone but two new types of chromosomes had emerged. Fluorescent probes detected Arabidopsis, but not human, DNA in the new types of chromosomes. They also detected signs of the formation of a human centromere—a structure found in chromosomes that’s crucial for cell division. Meanwhile, DNA microarray experiments revealed that the hybrid cells expressed 462 Arabidopsis genes, primarily from the three chromosomes that were apparently incorporated into the genome. “We found that plant chromosomes can be controlled by human control elements,” Oshimura says; the plant’s control elements were not part of the genes that were expressed. These findings suggest that the machinery for cell division and gene expression has been conserved between plants and humans—organisms separated by a vast evolutionary distance.

Oshimura envisions using these hybrid cells to understand the evolution of chromosome function from plants to humans, as well as to modify plant chromosomes, which could have agricultural applications. Modifying chromosomes is much easier in animal cells than in plant cells, so scientists could perhaps modify plant chromosomes in the hybrid cells and shuttle them back into plants.

James A. Birchler of the University of Missouri doubts that will be possible soon, since we still don’t have a way to transfer modified chromosomes from human cells back into plant cells. But the hybrid cells could yield insights into the evolution of gene expression, he says. Further experiments could investigate how faithfully the cells transcribe the Arabidopsis DNA to RNA and why transcription might go awry. “There are evolutionary questions that might be interesting to pursue.”

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