University of Tokyo: algal genome of 20 chromosomes retained in hamster and human cells in culture
Researchers fused the red alga Cyanidioschyzon merolae with cultured hamster and human cells; the algal DNA persisted without selection for 95 generations, silenced by methylation.
A group from the University of Tokyo reported in Nature Communications that mammalian cells in culture can acquire and keep genome-scale DNA from an alga. The donor was the red microalga Cyanidioschyzon merolae, whose genome is spread over 20 chromosomes. The recipients were Chinese hamster ovary cells and a human cell line derived from a connective-tissue tumour nature.com
Nature Communicationsnature.comOpen source ↗. The hybrid cells held more than 16 Mb of algal DNA, including intact chromosomes.
Fusion and uptake
The authors tested two routes: phagocytic uptake of intact algal cells and cell fusion with polyethylene glycol. Uptake worked at a much lower frequency than fusion. According to the publication's retelling, fusion gave on average 3098 resistant colonies per 12 million cells, while uptake gave 3.7.
The work produced 31 stable hybrid lines: 18 from hamster cells and 13 from human cells. In hamster cells most of the algal genome was transferred, and one line received all of it. Human cells were more selective. Live-cell imaging captured the early appearance of algal DNA in the nucleus after fusion.
The algal DNA was kept as telomere-linked structures attached to the host chromosomes. The cells divided for 155 generations under antibiotic selection. After the antibiotic was removed, the algal DNA persisted for another 95 generations without selection nature.com
Nature Communicationsnature.comOpen source ↗. The chloroplasts degraded during fusion, the cells did not photosynthesize, and they grew like ordinary animal cell cultures.
Methylation as a gatekeeper
The transferred algal DNA showed a progressive increase in DNA methylation and enrichment of repressive histone modifications. It formed heterochromatic domains that physically associate with host chromosomes. About 96% of the transferred algal genes showed no detectable expression. Among the host's own genes, 1.55% increased their activity and 0.33% decreased it.
The authors then used hamster cells deficient in DNMT3A, a de novo DNA methyltransferase. These cells established fewer stable hybrid colonies and retained less algal DNA. The authors interpret this as a gatekeeping role for DNA methylation in the stable accommodation of foreign genomes. They describe it as an epigenetic mechanism that contributes to the accommodation of large-scale foreign DNA between distantly related eukaryotes.
All experiments were carried out in cultured cells.
