AT FIRST sight, it shouldn’t be alive: a single-celled organism that lacks most of the molecular equipment needed to kick-start DNA replication.
Duplicating DNA is fundamental to reproduction, so DNA replication systems were thought to be present in all non-parasitic species with complex cells. But it seems they aren’t.
“I was astonished,” says Dayana Salas-Leiva at Dalhousie University in Halifax, Canada. The microbe, Carpediemonas membranifera, must have a mechanism for copying its DNA that is unknown to science.
C. membranifera is a single-celled organism, but it is a eukaryote, so its cell is large and complex like those of animals and plants. It lives in low-oxygen sediments.
As part of a general study of the microbe’s biology, Salas-Leiva and her colleagues sequenced its genome. They were baffled to find several genes missing, including some that code for the proteins that start DNA replication. Until now, all free-living eukaryotes that have been sequenced have had these.
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The researchers wondered if they had failed to sequence the genome thoroughly enough, so they spent a year redoing the work. “To this day, I cannot get those genes,” says Salas-Leiva.
“They sequenced the genome of this organism really well and really deeply,” says Vladimír Hampl at Charles University in the Czech Republic. “I believe it.”
C. membranifera does have polymerases, the enzymes that copy one strand of DNA to make a new one. But to kick-start the copying process, a group of proteins that form the origin recognition complex (ORC) – plus another protein called Cdc6 – must assemble at specific sites on the DNA strand. All of these proteins are missing in C. membranifera.
“It’s such a textbook thing, that eukaryotes have ORC,” says Michelle Hawkins at the University of York, UK. “To find something that doesn’t have it, that’s cool.”
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The most likely explanation is that C. membranifera has another mechanism for starting DNA replication, says Salas-Leiva.
Organisms do have repair mechanisms to copy DNA if a section of the genome gets damaged or lost. Salas-Leiva and her colleagues think C. membranifera may have cobbled them together with other proteins to copy the entire genome – although this might lead to a lot of mistakes during replication.
“It’s plausible,” says Hawkins. “I think each step has been shown somewhere else in a different species.” The next task will be to find out if this is really happening in C. membranifera cells.
The lack of the standard DNA replication system isn’t the only oddity about the microbe. C. membranifera is missing proteins that help move DNA around when cells divide so that both new cells get copies of every gene. It is unclear how the organism copes. “We are very perplexed,” says Salas-Leiva.
Reference: bioRxiv, DOI: 10.1101/2021.03.14.435266