Unicellular Organism Is Missing Genes That Are Vital to Copying and Distributing Its DNA

If there is one process that a cell must do right, it is copying its DNA before division, and making sure that the chromosomes are distributed properly to the daughter cells. This is even more important for unicellular organisms. Yet, Carpediemonas membranifera, a unicellular organism that lives on marine shorelines, misses genes that are vital to copying and distributing its DNA. Eelco Tromer, an evolutionary cell biologist at the University of Groningen, was part of the team that described this strange creature in Nature Communications on 14 October.

‘My expertise is finding genes that other people can’t see,’ says Tromer. He recently moved from the University of Cambridge to the University of Groningen, after receiving a Veni grant from the Dutch Research Council (NWO). Recently, his Canadian colleagues searched for but could not find some vital genes in the free-living protist Carpediemonas membranifera. ‘It lives on the seabed in intertidal sediments that are low in oxygen, where it feeds on bacteria,’ explains Tromer. Some groups of single-cell protists that live in the sea have lost all or some of their mitochondria, the energy factories that need oxygen to function. Surprisingly, however, the genes that were lost in Carpediemonas were involved in DNA replication and chromosome segregation.

Protein complex

Some parasites which have lost genes that code for proteins that are needed in copying and segregating DNA may use host proteins instead. To find a free-living eukaryotic cell, which has a nucleus just like our cells, without these proteins was unexpected. Therefore, Tromer was asked for a second opinion. He uses software programs and has a lot of knowledge about molecular evolution. ‘I have previously studied the loss of genes that code for the kinetochore, a protein complex that is involved in separating chromosomes during cell division.’ With his experience and programs, he can recognize genes that have changed significantly. But in this case, he could not 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 is some precedent for missing otherwise conserved parts.’ However, the protist was also missing some genes that are vital to the copying of 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 that there is some other molecular system that has taken over this function.’

Flexible

Tromer has not been able to pinpoint how the protist can thrive without these genes. ‘This organism is tricky to culture; it has a diet of specific bacteria and needs an almost oxygen-free environment.’ C. membranifera has not been studied extensively, and consequently, very few research tools have been developed to probe its genome. ‘We might have to turn to some more basic, old-fashioned techniques to study the protein complexes in Carpediemonas,’ 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 may assume that it is present in all eukaryotes. Yet there are exceptions, as a lot of unicellular eukaryotes are much further removed from humans than yeast.’ This makes the reconstruction of the last common ancestor of all eukaryotes more complex.

AlhpaFold

All this does not explain how a cell can survive without the conventional genes for DNA replication and chromosome segregation. ‘I have only looked at genetic data. However, similar proteins can arise from a highly divergent genetic code.’ In that case, Tromer would not recognize the gene as one involved in the copying of DNA or distribution of chromosomes. ‘Maybe we can use the recently developed AlphaFold program, which predicts the 3D structure of proteins based on the genetic sequence. But that is likely to 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: Salas-Leiva DE, Tromer EC, Curtis BA, et al. Genomic analysis finds no evidence of canonical eukaryotic DNA processing complexes in a free-living protist. Nat Commun. 2021;12(1):6003. doi: 10.1038/s41467-021-26077-2

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