Genega, or how we require all of our genes to survive

I went to a birthday gathering in a pub the other day to which someone had brought along the game Jenga. Putting aside any conclusions you may want to make as to just how exciting it must be to party with my friends and me, the game actually illustrates an interesting point about evolution. Sort of. 

The idea of Jenga is that you stack up these little sticks of wood and, taking turns, pull out the pieces one at a time in the hope that you won’t collapse the entire tower. If you’re very careful (and haven’t had more than one pint), it is possible to strip down the tower to the bare minimum of pieces that are required to keep it upright. But pick one of the essential load-bearing pieces and the whole thing comes crashing down on top of everyone’s drinks.

And, in a way, evolution is playing Jenga with our genes.

Jenga - image from Wikipedia Commons

You’d think that, after millions of years, our genomes would be stripped-down, streamlined collections of only the DNA we require to be us; nothing more, nothing less. This hypothesis is backed up by the fact that almost all the genes in eukaryotic genomes are conserved—this means that they are found across many species and have persisted in the population for far longer than you’d expect if they weren’t absolutely necessary for survival. The loss of non-essential genes can actually be seen in many parasitic species. The leprosy bacterium, for example, is a much reduced version of the microbe which causes tuberculosis. It has lost around half of its genes because it doesn’t need them anymore.

But here's the problem: scientists have known for ages that it is possible to delete many of the genes found in eukaryotic organisms with no noticeable effect. So a group at the University of Toronto decided to address the question of whether the C. elegans worm really needs all its genes, and their work was recently published in Cell.

C. elegans - Image is from Wikipedia Commons.

The method used by this group was especially clever because, instead of deleting single genes and looking at whether the worm survives, they tested the effect of gene loss over several generations and in competition with other worms. After all, this is what happens during evolution—survival of the fittest and all that. The basic method showcased in this paper used something known as RNA interference to knock-down the effects of a certain gene (RNA interference literally interferes with the synthesis of a protein by sequestering away the mRNA recipe before it can give the cell any instructions).

The scientists mixed those worms in which a gene had been knocked-down with the original worms. If the gene being tested proves to be vital, the knocked-down worms will be lost over successive generations due to competition with the original, fitter worms. And, fitting with the idea that we (and by ‘we’ I am referring to all eukaryotes including worms; some people are more worm-like than others, though) only have the genes we need to survive, nearly all the genes in C. elegans were found to impact fitness when knocked down.

This is not what was suggested from all the experiments in which it was found that single genes could be deleted without any obvious effect on the organism. The explanation is probably that different genes play a role under different conditions. This would mean that it might be possible for one gene to be deleted in the laboratory but, were the mutant to be let out into the big wide world, with all its various stresses and challenges, it would be seriously impaired in its survival.

Interestingly, many more genes are found to be essential when this method is used in C. elegans than are identified by similar experiments in yeast. The authors of this paper suggest that this is down to selective pressures being very different for single and multi-cellular organisms. Whereas something like yeast only has to deal with one environmental condition at one time, a multi-cellular organism is forced to juggle the needs of lots of different cell types which are all under different pressures of their own. A multi-cellular creature is far more complex than a unicellular organism and the genes required are therefore more finely tuned. A little like playing Jenga on not just a tower but an entire city and…OK, the analogy is collapsing all around me so I am going to give up and have a drink instead.