A database of proteins, known as the “unknome”, has revealed that there is still a vast amount of information that remains unknown about thousands of human proteins. The team behind the database has also discovered that some of these proteins are crucial for our survival.
Researchers at the MRC Laboratory of Molecular Biology in Cambridge, UK, led by Sean Munro, created the unknome database by starting with the approximately 20,000 genes that code for proteins identified in humans. They grouped closely related human genes and proteins together, based on the assumption that they have similar functions, resulting in around 7,500 protein clusters.
The researchers then added closely related proteins from commonly studied animals, such as mice and fruit flies, to these clusters, assuming that they also have similar functions. Each protein cluster was given a score based on the number of entries about its members in the main repository of gene function information, called the Gene Ontology Resource.
A human protein that has not been directly studied can still receive a high score if an equivalent protein from another animal has been extensively studied. The score also takes into account the reliability of the entries, such as whether they have been published in a journal. However, the scoring is somewhat arbitrary, as it is challenging to determine what we don’t know.
The best-studied proteins have scores well above 100, such as the protein sonic hedgehog, involved in embryonic development, with a score of 168, and the protein p53, which helps prevent cells from becoming cancerous, with a score of 126. On the other hand, over 2,200 proteins have scores below 2, with 1,100 scoring below 1, and more than 800 scoring 0.
To assess the importance of these low-scoring proteins, the researchers used a technique called RNA interference (RNAi) to reduce the levels of 260 proteins with scores below 1 in fruit flies. They found that in 60 cases, the fruit flies died, indicating that these specific proteins have essential functions.
This discovery surprised the researchers who study fruit flies, as they previously assumed that all significant genes in these organisms had been identified, which turned out to be untrue.
Although the number of unknown proteins is gradually decreasing, Munro hopes that these findings will speed up our understanding of them. The challenge lies in the reluctance of both funding bodies and individual researchers to study unknown proteins, fearing that they may not be important.
Munro highlights that there may be biological processes and proteins that we are unaware of because we are not actively searching for them. He cites the example of CRISPR, a gene-editing technique based on bacterial proteins whose function was only discovered in 2012.
Data
- Total number of identified genes for proteins in humans: Around 20,000
- Number of protein clusters in the unknome database: Around 7,500
- Proteins with scores above 100: The best-studied proteins
- Proteins with scores below 2: Over 2,200
- Proteins with scores below 1: 1,100
- Proteins with scores of 0: Over 800
- Number of proteins with scores below 1 tested in fruit flies: 260
- Fruit flies that died when levels of proteins below 1 were reduced: 60
