The relationship between proteome size, structural disorder and organism complexity

We revisited the G-value paradox by analyzing many new proteomes whose complexity measured with their number of distinct cell types is known. We found that complexity and proteome size measured by the total number of amino acids correlate significantly and have a power function relationship. We systematically analyzed numerous other features in relation to complexity in several organisms and tissues and found: the fraction of protein structural disorder increases significantly between prokaryotes and eukaryotes but does not further increase over the course of evolution; the number of predicted binding sites in disordered regions in a proteome increases with complexity; the fraction of protein disorder, predicted binding sites, alternative splicing and protein-protein interactions all increase with the complexity of human tissues.We conclude that complexity is a multi-parametric trait, determined by interaction potential, alternative splicing capacity, tissue-specific protein disorder and, above all, proteome size. The G-value paradox is only apparent when plants are grouped with metazoans, as they have a different relationship between complexity and proteome size.Biological complexity is a feature that increases during evolution, distinguishing us from more primitive forms of life. Whereas it has no straightforward definition, it is generally accepted that it can be measured by the number of different cell types in an organism ranging from 1 (bacteria) to about 200 (humans) [1-4]. As complexity is apparently related to the amount of information an organism needs to function properly, and such information is contained in our genes, it was generally expected that the number of genes correlates with biological complexity. This was called into doubt and referred to as the G-value paradox [5]. There have been numerous attempts to resolve the paradox, citing multifunctionality of proteins [6], microRNAs [7], non-protein-coding DNA [8] or alternative splicing [9]. In this