My professor Pierluigi Luisi used to say: “Why this and not that?”  when speaking about proteins. The underlining question was about the emergence and fixation of protein sequences in extant organisms. There might be some 10^14 different protein sequences in the biosphere today, yet this apparently huge number represents only an infinitesimal fraction of all theoretically possible proteins. Just to give an example, there are some 10^65 theoretically different proteins 50 amino acids long. The number of extant proteins represents a “grain of sand in the Sahara”  when compare to the number of possible ones.
Do extant proteins have any particular features that make them eligible for selection? Or are they the sheer outcome of chance? Are extant proteins the exquisite result of natural selection or are they random sequences slightly edited by evolution?
In our latest work , we address this question by comparing a set of 762 natural proteins with an average length of 70 amino acids and an equal number of completely random ones of comparable length on the basis of their structural features. Our results suggest that random proteins are significantly different from extant ones, yet they display inherent conformational order which derives from chemico-physical constrains rather than from natural selection. This intrinsic order represents a “free-ticket” to start the adaptation process to specific functions and environments.
1. Pier Luigi Luisi The Emergence of Life. From Chemical Origins to Synthetic Biology. Cambridge University Press. 2006
2. De Lucrezia D, Slanzi D, Poli I, Polticelli F, Minervini G. Do Natural Proteins Differ from Random Sequences Polypeptides? Natural vs. Random Proteins Classification Using an evolutionary Neural Network. PLoS ONE, 2012. 7(5)