We still have no idea what 20 per cent of protein-coding genes are for. What’s more, we’ve stopped making progress, according to a study looking at what we know about yeast and human proteins.
“Basically we really don’t have a clue,” says team leader Valerie Wood of the University of Cambridge in the UK.
Her team started by defining what is known or unknown. For instance, we might be able to tell that a protein is an enzyme from its sequence, but if we don’t know what reaction it catalyses its function cannot be said to be known. Wood compares it to taking a car to pieces – recognising that one piece is, say, a wire is not much help understanding what it’s for.
When the team applied these criteria to yeast proteins, they found that the function of most of them was discovered in the 1990s. Progress slowed in the 2000s and plateaued in the 2010s with the function of a fifth still unknown.
Next the team showed that the same proportion of human protein-coding genes remain a mystery. “There are 3000 human proteins whose function is unknown,” says Wood.
The team did not look at the rate of progress for human proteins, but Wood thinks the situation is similar. There are two reasons why progress is grinding to a halt, she says.
Firstly, a common way to find out what protein-coding genes do is to mutate them in animals such as mice and zebrafish to see what happens. The mystery proteins don’t show up in these screens, perhaps because they are involved in processes such as ageing whose effects are subtle.
Secondly, funders are turning down applications to study these unknown proteins because of the risk of people spending years working on them without any results.
That might be a mistake. Wood’s team also showed that a quarter of the mystery proteins in humans are also found in yeast. That means these proteins have been conserved over the billion years or so since the our ancestors split from those of yeast.
“They must be doing something pretty important,” says Wood. “I’m absolutely certain there are big discoveries to be made.”
Journal reference: Open Biology, DOI: 10.1098/rsob.180241
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