Do Natural Proteins Differ from Random Sequences Polypeptides? Natural vs. Random Proteins Classification Using an Evolutionary Neural Network

Are extant proteins the exquisite result of natural selection or are they random sequences slightly edited by evolution? This question has puzzled biochemists for long time and several groups have addressed this issue comparing natural protein sequences to completely random ones coming to contradicting conclusions. Previous works in literature focused on the analysis of primary structure in an attempt to identify possible signature of evolutionary editing. Conversely, in this work we compare 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. We use an ad hoc Evolutionary Neural Network Algorithm (ENNA) in order to assess whether and to what extent natural proteins are edited from random polypeptides employing 11 different structure-related variables (i.e. net charge, volume, surface area, coil, alpha helix, beta sheet, percentage of coil, percentage of alpha helix, percentage of beta sheet, percentage of secondary structure and surface hydrophobicity). The ENNA algorithm is capable to correctly distinguish natural proteins from random ones with an accuracy of 94.36%. Furthermore, we study the structural features of 32 random polypeptides misclassified as natural ones to unveil any structural similarity to natural proteins. Results show that random proteins misclassified by the ENNA algorithm exhibit a significant fold similarity to portions or subdomains of extant proteins at atomic resolution. Altogether, our results suggest that natural proteins are significantly edited from random polypeptides and evolutionary editing can be readily detected analyzing structural features. Furthermore, we also show that the ENNA, employing simple structural descriptors, can predict whether a protein chain is natural or random

The Problem of the "Prebiotic and Never Born Proteins"

It has been argued that the limited set of proteins used by life as we know it could not have arisen by the process of Darwinian selection from all possible proteins. This probabilistic argument has a number of implicit assumptions that may not be warranted. A variety of considerations are presented to show that the number of amino-acid sequences that need have been sampled during the evolution of proteins is far smaller than assumed by the argument.Comment: 14 Pages; International Journal of Astrobiology / FirstView Article / October 2012, pp 1

The role of backward reactions in a stochastic model of catalytic reaction networks

We investigate the role of backward reactions in a stochastic model of catalytic reaction network, with specific regard to the influence on the emergence of autocatalytic sets (ACSs), which are supposed to be one of the pre-requisites in the transition between non-living to living matter. In particular, we analyse the impact that a variation in the kinetic rates of forward and backward reactions may have on the overall dynamics. Significant effects are indeed observed, provided that the intensity of backward reactions is sufficiently high. In spite of an invariant activity of the system in terms of production of new species, as backward reactions are intensified, the emergence of ACSs becomes more likely and an increase in their number, as well as in the proportion of species belonging to them, is observed. Furthermore, ACSs appear to be more robust to fluctuations than in the usual settings with no backward reaction. This outcome may rely not only on the higher average connectivity of the reaction graph, but also on the distinguishing property of backward reactions of recreating the substrates of the corresponding forward reactions

Entropy of never born protein sequences

BACKGROUND: A Never Born protein is a theoretical protein which does not occur in nature. The reason why some proteins were selected and some were not during evolution is not known. We applied information theory to find similarities and differences in information content in Never Born and natural proteins. FINDINGS: Both block and relative entropies are similar what means that both protein kinds contain strongly random sequences. An artificially generated Never Born protein sequence is closely as random as a natural one. CONCLUSIONS: Information theory approach suggests that protein selection during evolution was rather random/non-deterministic. Natural proteins have no noticeable unique features in information theory sense. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-200) contains supplementary material, which is available to authorized users

How much of protein sequence space has been explored by life on Earth?

We suggest that the vastness of protein sequence space is actually completely explorable during the populating of the Earth by life by considering upper and lower limits for the number of organisms, genome size, mutation rate and the number of functionally distinct classes of amino acids. We conclude that rather than life having explored only an infinitesimally small part of sequence space in the last 4 Gyr, it is instead quite plausible for all of functional protein sequence space to have been explored and that furthermore, at the molecular level, there is no role for contingency

Can life be standardized? : current challenges in biological standardization

The concept of standard strongly evokes machines, industries, electric or mechanical devices, vehicles, or furniture. Indeed, our technological civilization would not be possible ? at least in the terms it is structured today ? without universal, reliable components, whose acknowledged use results in competitive costs, robustness and interchangeability. For example, an Ikea screw can be used in a wide set of structurally dissimilar furniture and an app can be run on many different smartphones. The very concept of standardization is linked to the industrial revolution and mass production of goods through assembly lines. The question we will try to answer in the present paper is the extent to which standards and the standardization process can be accomplished in the biological realm

DNA Movies and Panspermia

There are several ways that our species might try to send a message to another species separated from us by space and/or time. Synthetic biology might be used to write an epitaph to our species, or simply “Kilroy was here”, in the genome of a bacterium via the patterns of either (1) the codons to exploit Life's non-equilibrium character or (2) the bases themselves to exploit Life's quasi-equilibrium character. We suggest here how DNA movies might be designed using such patterns. We also suggest that a search for mechanisms to create and preserve such patterns might lead to a better understanding of modern cells. Finally, we argue that the cutting-edge microbiology and synthetic biology needed for the Kilroy project would put origin-of-life studies in the vanguard of research