Cell Study Challenges Long-Standing View That Individual Human Genomes Evolve Independently

Scientists at Children's Medical Center Research Institute at UT Southwestern (CRI) have discovered that large pieces of DNA can transfer directly between human cells, and the DNA can persist and change how the recipient cell functions. The findings, published today in Cell, challenge a long-standing view that the genomes of individual human cells evolve independently from one another.

The study shows DNA damage and errors in cell division can cause pieces of genomic DNA to escape from the nucleus and move into nearby cells through nanotubes – thin, tubelike structures that briefly form when some cells come into contact.

Once inside a recipient cell, transferred DNA can enter the nucleus and become incorporated into the cell's genome. Researchers found that transferred DNA persisted through multiple rounds of cell division, remained biologically active, and conferred new traits to recipient cells.

"This was a surprising discovery," said study leader Peter Ly, Ph.D., Assistant Professor in CRI and of Cell Biology, Pediatrics, and in the Harold C. Simmons Comprehensive Cancer Center.

Our findings suggest neighboring cells may be able to directly reshape one another's genomes in ways we did not anticipate."

Peter Ly, Harold C. Simmons Comprehensive Cancer Center

Study first author Elizabeth Maurais, Ph.D., a recent graduate of the Genetics, Development and Disease Program at UT Southwestern, and other Ly Lab researchers uncovered this process while studying how cells respond to genomic instability, including DNA damage caused by chemotherapy and radiation treatment.

Using advanced live-cell microscopy, the team observed DNA moving from one cell to another. In one experiment, pieces of the Y chromosome transferred from male cells into female cells. The transferred DNA carried male-specific genes that became active in the female cells, indicating the transferred DNA remained functional after entering the recipient cell.

"There are many open questions. We now want to understand how widespread this process is, how it is regulated at the cellular and molecular levels, and what role it may play in human health and disease, including cancer," Dr. Ly said. "These findings may have important implications for understanding how cancer genomes evolve and acquire large-scale chromosomal alterations."

Researchers also observed DNA transfer between different types of human cells, which Dr. Ly said suggests the findings may be a general feature of human cell biology. 

This research was funded by the National Institutes of Health (NIH), the Cancer Prevention and Research Institute of Texas (CPRIT), the U.S. Department of Defense, The Welch Foundation, a UT Southwestern Haberecht Wildhare-Idea Research Grant, a UT Southwestern Synergy Grant for Collaborative Research, and the Oklahoma Center for Adult Stem Cell Research.

Dr. Ly is a CPRIT Scholar in Cancer Research. Dr. Maurais received an NIH Ruth L. Kirschstein Predoctoral Fellowship from the National Cancer Institute.