42: The Answer to Life, the Universe and... the Number of Proteins in a Cell?

Arthur Dent, hero of Douglas Adams’ seminal sci-fi series The Hitchhiker’s Guide to the Galaxy, spent a large chunk of his time running around trying to find the Answer to the Ultimate Question of Life, The Universe, and Everything. In the books’ highly irreverent logic, the Ultimate Question ended up being: 

“What do you get if you multiply six by nine?” to which Arthur cheerily responds “42”. 

42 may not actually be the correct answer to that question, or to most important questions in life, but it is the answer that a group of scientists at the University of Toronto found when trying to answer their own age-old question: how many proteins can be found in a cell? 

Protein Numbers Need Normalizing 

Proteins are the material that make up our cells and undertake most of the work that goes on in them. Despite the vast volume of research into the function and form of proteins, no study has been able to work out how many of these previous molecules there are in each cell. 

This, said study author and graduate student Brandon Ho, was partially because different research groups use such varying and incomparable methods to calculate cell measurements: "It was hard to conceptualize how many proteins there are in the cell because the data was reported on drastically different scales.” 

The team set out to take all the differing methods convert their calculations into, as lead author Grant Brown puts it "something that makes sense, in other words, molecules per cell,". 

The Best Friend of Bakers, Brewers and Biologists

To reduce all this complication, the team started with something simple. Saccharomyces cerevisiae (aka. baker’s yeast) actually has a double life as one of cell science’s most popular study organisms when it’s not busy making beer or bread (which makes this discovery the best thing since the toaster-knife).

S. cerevisiae was the first eukaryote (the domain of life that contains all living things apart from bacteria and archaea) to have its entire genome read, so it’s well-tread territory for many microbiologists. This gave the Toronto 21 huge studies from other research groups, all of which had used different techniques to try and calculate protein number.

42 Million Protein Molecules Per Cell 

After establishing that molecules per cell was the best yardstick to measure protein number by, the team normalized the vast trove of data at their fingertips to produce a definitive answer – 42 million molecules per cell, split over 5,858 different types of protein.

The team also noticed that each of these types of protein are not evenly represented, with some proteins packing nearly 500,000 copies into each cell, and others barely even present at all, totaling a meagre 10 molecules per cell. 

This research will help scientists build up a picture of what the collection of all a cell’s proteins, (the proteome), looks like and has also provided valuable information of how cells control protein abundance, which can be used to help cure diseases where cell protein number or function goes haywire, such as Alzheimer’s disease or Parkinson’s. 

Douglas Adams may have not thought much about his key number (he picked it at random whilst looking at his garden) but it looks like 42 has some real-world significance after all.