Mysterious organism lacks genes vital to copying DNA

If there is one thing a cell has to do right, it is copying its DNA before division. When you’re a unicellular organism, it is even more important that both daughter cells receive all the chromosomes. Yet Carpediemonas membranifera, a unicellular organism that lives on ocean beds misses genes that are vital to copying and distributing its DNA. University of Groningen molecular cell biologist Eelco Tromer was part of the team that described this strange creature in Nature Communications on 14 October.

‘My specialty is finding genes that everyone else can’t see’, says Tromer. He recently moved from Cambridge University to the University of Groningen, after receiving a Veni grant from the Dutch research council NWO.  When Canadian colleagues couldn’t find some vital genes in the free living protist Carpediemonas membranifera. ‘It lives at the bottom of oceans in water with little oxygen’, explains Tromer. Many organisms in de deep sea have lost their mitochondria, the energy factories which need oxygen to function.

Parts missing

Some parasites have lost genes that are needed in the copying of DNA, but they can use host proteins instead. To find a free living eukaryotic cell, with a nucleus just like our cells, without these proteins was unexpected. So Tromer was asked for a second opinion. His tools are software programs and a lot of knowledge about molecular evolution. ‘I have previously studied the loss of genes for the kinetochore, a protein complex which is involved in separating chromosomes during cell division.’ With his experience, he can recognize genes that have changed a lot. But in this case, he couldn’t find them either.

Tromer confirmed that the protist C. membranifera lacked some of the genes that code for kinetochore proteins. ‘This is not uncommon, as the kinetochore evolves very rapidly, so there are often parts missing.’ And the protist also lacked some genes that are vital to the copying of the chromosomes before cell division. ‘It lacks genes for a protein that finds the starting point for copying these chromosomes. But it is still able to copy its DNA, so we must assume there is some other protein which has taken over this function.’

Dogmas

Tomer hasn’t been able to pinpoint how the protist manages. ‘This organism is difficult to culture, they have a diet of very specific bacteria and need an almost oxygen-free environment.’ As a result, very little research has been done with it, so there are very few research tools available to deeper probe its DNA. ‘We have to use very basic, old fashioned techniques to study the protein complexes’, says Tromer.

The fact that vital genes are missing shows how flexible evolution can be. It also shows that some dogmas in molecular evolutionary biology are wrong, explains Tromer: ‘The idea was that if a gene is conserved between yeast and humans, you know it’s probably present in all eukaryotes. There are actually exceptions, as a lot of unicellular organisms are much further removed from humans than yeast.’ This makes the reconstruction of the putative last common ancestor of all eukaryotes more complex. It is this molecular evolution that drives Tromers research. ‘I am always trying to recognize patterns in genetic differences.’ Based on these patterns, he is able to group related species together.

AlphaFold

All this doesn’t explain how a cell can survive without the conventional genes for DNA replication and chromosome division. ‘I have only looked at genetic data. However, similar proteins can arise from different genetic codes. Maybe we can use the recently developed AlphaFold program, which predicts the 3D structure of proteins based on the genetic sequence. But that will take a lot of computing power.’ Fortunately, the University of Groningen operates some quite powerful systems. ‘So I’m trying to get this going.’

Reference: Dayana E. Salas-Leiva, Eelco C. Tromer, Bruce A. Curtis, Jon Jerlström-Hultqvist, Martin Kolisko, Zhenzhen Yi, Joan S. Salas-Leiva, Lucie Gallot-Lavallée, Shelby K. Williams, Geert J.P.L. Kops, John M. Archibald, Alastair G. B. Simpson and Andrew J. Roger: Genomic analysis finds no evidence of canonical eukaryotic DNA processing complexes in a free-living protist. Nature Communications, 14 October 2021