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Register a new userUniversal Sequence Replication, Reversible Polymerization and Early Functional Biopolymers: A Model for the Initiation of Prebiotic Sequence Evolution
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Many models for the origin of life have focused on understanding how evolution can drive the refinement of a preexisting enzyme, such as the evolution of efficient replicase activity. Here we present a model for what was, arguably, an even earlier stage of chemical evolution, when polymer sequence diversity was generated and sustained before, and during, the onset of functional selection. The model includes regular environmental cycles (e.g. hydration-dehydration cycles) that drive polymers between times of replication and functional activity, which coincide with times of different monomer and polymer diffusivity. Kinetic Monte Carlo simulations demonstrate that this proposed prebiotic scenario provides a robust mechanism for the exploration of sequence space. Introduction of a polymer sequence with monomer synthetase activity illustrates that functional sequences can become established in a preexisting pool of otherwise non-functional sequences. Functional selection does not dominate system dynamics and sequence diversity remains high, permitting the emergence and spread of more than one functional sequence. It is also observed that polymers spontaneously form clusters in simulations where polymers diffuse more slowly than monomers, a feature that is reminiscent of a previous proposal that the earliest stages of life could have been defined by the collective evolution of a system-wide cooperation of polymer aggregates. Overall, the results presented demonstrate the merits of considering plausible prebiotic polymer chemistries and environments that would have allowed for the rapid turnover of monomer resources and for regularly varying monomer/polymer diffusivities.
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The post-genomic era has brought opportunities to bridge traditionally separate fields of early history of life and brought new insight into origin and evolution of biodiversity. According to distributions of codons in genome sequences, I found a relationship between the genetic code and the tree of life. This remote and profound relationship involves the origin and evolution of the genetic code and the diversification and expansion of genomes. Here, a prebiotic picture of the triplex nucleic acid evolution is proposed to explain the origin of the genetic code, where the transition from disorder to order in the origin of life might be due to the increasing stabilities of triplex base pairs. The codon degeneracy can be obtained in detail based on the coevolution of the genetic code with amino acids, or equivalently, the coevolution of tRNAs with aaRSs. This theory is based on experimental data such as the stability of triplex base pairs and the statistical features of genomic codon distributions. Several experimentally testable proposals have been developed. This study should be regarded as an exploratory attempt to reveal the early evolution of life based on sequence information in a statistical manner.
Motivation: DNA data is transcribed into single-stranded RNA, which folds into specific molecular structures. In this paper we pose the question to what extent sequence- and structure-information correlate. We view this correlation as structural semantics of sequence data that allows for a different interpretation than conventional sequence alignment. Structural semantics could enable us to identify more general embedded patterns in DNA and RNA sequences. Results: We compute the partition function of sequences with respect to a fixed structure and connect this computation to the mutual information of a sequence-structure pair for RNA secondary structures. We present a Boltzmann sampler and obtain the a priori probability of specific sequence patterns. We present a detailed analysis for the three PDB-structures, 2JXV (hairpin), 2N3R (3-branch multi-loop) and 1EHZ (tRNA). We localize specific sequence patterns, contrast the energy spectrum of the Boltzmann sampled sequences versus those sequences that refold into the same structure and derive a criterion to identify native structures. We illustrate that there are multiple sequences in the partition function of a fixed structure, each having nearly the same mutual information, that are nevertheless poorly aligned. This indicates the possibility of the existence of relevant patterns embedded in the sequences that are not discoverable using alignments.
We develop a robust coarse-grained model for single and double stranded DNA by representing each nucleotide by three interaction sites (TIS) located at the centers of mass of sugar, phosphate, and base. The resulting TIS model includes base-stacking, hydrogen bond, and electrostatic interactions as well as bond-stretching and bond angle potentials that account for the polymeric nature of DNA. The choices of force constants for stretching and the bending potentials were guided by a Boltzmann inversion procedure using a large representative set of DNA structures extracted from the Protein Data Bank. Some of the parameters in the stacking interactions were calculated using a learning procedure, which ensured that the experimentally measured melting temperatures of dimers are faithfully reproduced. Without any further adjustments, the calculations based on the TIS model reproduces the experimentally measured salt and sequence dependence of the size of single stranded DNA (ssDNA), as well as the persistence lengths of poly(dA) and poly(dT) chains. Interestingly, upon application of mechanical force the extension of poly(dA) exhibits a plateau, which we trace to the formation of stacked helical domains. In contrast, the force-extension curve (FEC) of poly(dT) is entropic in origin, and could be described by a standard polymer model. We also show that the persistence length of double stranded DNA is consistent with the prediction based on the worm-like chain. The persistence length, which decreases with increasing salt concentration, is in accord with the Odijk-Skolnick-Fixman theory intended for stiff polyelectrolyte chains near the rod limit. The range of applications, which did not require adjusting any parameter after the initial construction based solely on PDB structures and melting profiles of dimers, attests to the transferability and robustness of the TIS model for ssDNA and dsDNA.
Sequence-to-sequence (seq2seq) problems such as machine translation are bidirectional, which naturally derive a pair of directional tasks and two directional learning signals. However, typical seq2seq neural networks are {em simplex} that only model one unidirectional task, which cannot fully exploit the potential of bidirectional learning signals from parallel data. To address this issue, we propose a {em duplex} seq2seq neural network, REDER (Reversible Duplex Transformer), and apply it to machine translation. The architecture of REDER has two ends, each of which specializes in a language so as to read and yield sequences in that language. As a result, REDER can simultaneously learn from the bidirectional signals, and enables {em reversible machine translation} by simply flipping the input and output ends, Experiments on widely-used machine translation benchmarks verify that REDER achieves the first success of reversible machine translation, which helps obtain considerable gains over several strong baselines.
Proteins employ the information stored in the genetic code and translated into their sequences to carry out well-defined functions in the cellular environment. The possibility to encode for such functions is controlled by the balance between the amount of information supplied by the sequence and that left after that the protein has folded into its structure. We developed a computational algorithm to evaluate the amount of information necessary to specify the protein structure, keeping into account the thermodynamic properties of protein folding. We thus show that the information remaining in the protein sequence after encoding for its structure (the information gap) is very close to what needed to encode for its function and interactions. Then, by predicting the information gap directly from the protein sequence, we show that it may be possible to use these insights from information theory to discriminate between ordered and disordered proteins, to identify unknown functions, and to optimize designed proteins sequences.
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