PomBase researchers have published a new paper in Open Biology suggesting important roles in long-term survival for conserved proteins of unknown function.
Have you ever completed a jigsaw puzzle and found that you are missing some critical pieces, say those needed to complete a face or an important building? It's very frustrating, but that is exactly the situation in which the world's biologists find themselves. With the completion of the genetic blueprints (the genome sequences) of organisms ranging from bacteria and yeasts up to human beings, it was hoped that we would have a complete inventory of the working parts, mainly proteins, required for life. To some extent this is true - we do have such inventories. However, unlike the list of parts for your car or washing machine, we don't understand what many of these biological components are for. We do know that proteins are large molecules that perform a vast array of functions within organisms, from catalysing metabolic reactions, to copying DNA, building cells, and transporting molecules from one location to another. Nevertheless, despite intensive work since the genome-sequencing era began in the early 1990s to characterise the proteins encoded by humans and other species, many proteins remain poorly understood with respect to their particular biological roles.
Researchers at both the University of Cambridge and University College London collaborate on PomBase, a catalogue of the roles of proteins in the fission yeast Schizosaccharomyces pombe. They have found that the rate of increase in the number of proteins with characterised functions has almost flat-lined over the past decade. This is in comparison to a period of intensive discovery from 1990-2006 when the proportion of all proteins characterised increased from 20% to around 70%. When looking at the percentage of characterised proteins in baker's yeast and humans, a similar pattern emerges; around 20% of proteins have no known biological role.
Unknown proteins are often assumed to be involved in processes that are specific to the species concerned, or to its close relatives. However, in their new study, Valerie Wood and colleagues show that many of these proteins are conserved across many species, some from ancient bacteria and yeasts to humans, and so they are likely to play fundamentally important roles in all forms of life. The authors then classified fission yeast proteins based on a combination of attributes (e.g. conservation among broad biological kingdoms, importance for survival, localisation in the cell, catalytic activity) to identify any patterns in available knowledge that might provide clues as to the cellular functions for these proteins. The PomBase team's analyses reveal that these conserved proteins of unknown function may play important roles in long-term survival, dealing with the accumulation of damaged or mis-folded proteins, or toxic metabolites. In humans, these functions are involved in neurodegenerative diseases, such as Alzheimer's and Motor Neurone Disease, which biomedical science is struggling to get to grips with. This suggests that it is imperative for both researchers and research funders to pay renewed attention to these 'conserved unknowns' in order to finish the jigsaw of life.