Degeneracy and genetic assimilation in RNA evolution.

BACKGROUND: The neutral theory of Motoo Kimura stipulates that evolution is mostly driven by neutral mutations. However adaptive pressure eventually leads to changes in phenotype that involve non-neutral mutations. The relation between neutrality and adaptation has been studied in the context of RNA before and here we further study transitional mutations in the context of degenerate (plastic) RNA sequences and genetic assimilation. We propose quasineutral mutations, i.e. mutations which preserve an element of the phenotype set, as minimal mutations and study their properties. We also propose a general probabilistic interpretation of genetic assimilation and specialize it to the Boltzmann ensemble of RNA sequences. RESULTS: We show that degenerate sequences i.e. sequences with more than one structure at the MFE level have the highest evolvability among all sequences and are central to evolutionary innovation. Degenerate sequences also tend to cluster together in the sequence space. The selective pressure in an evolutionary simulation causes the population to move towards regions with more degenerate sequences, i.e. regions at the intersection of different neutral networks, and this causes the number of such sequences to increase well beyond the average percentage of degenerate sequences in the sequence space. We also observe that evolution by quasineutral mutations tends to conserve the number of base pairs in structures and thereby maintains structural integrity even in the presence of pressure to the contrary. CONCLUSIONS: We conclude that degenerate RNA sequences play a major role in evolutionary adaptation.

Multiplicity of phenotypes and RNA evolution.

Motivation Motoo Kimura's neutral theory stipulates that evolution is predominantly driven by neutral mutations. RNA, realizing both genotype (its linear sequence of nucleotides) as well as phenotype (its folded secondary structure) represents a particularly well suited test bed for studying neutrality. This leads to neutral networks of RNA secondary structures, i.e. sets of sequences all of which folding into a fixed phenotype and whose organization plays a crucial role for neutral evolution. In this paper we bring a new perspective to the neutral theory by studying the consequences of the mostly ignored fact that the genotype-to-phenotype map for RNA is often one-to-many. In fact 29.5% of random RNA sequences realize more than one phenotype (minimum free energy structure). We call two genotypes to be quasineutral if their sets of associated phenotypes have non-empty intersection. Results We show that even though the energy profile of quasineutral mutations is almost identical to the neutral ones, a walk in the genotype space whose consecutive steps are quasineutral, can percolate phenotype space and so such walks bridge between neutral and random walks. This provides further evidence that evolution is continuous. We also study how these drift walks transition between neutral networks.

Hydrogen bond rotations as a uniform structural tool for analyzing protein architecture.

Proteins fold into three-dimensional structures, which determine their diverse functions. The conformation of the backbone of each structure is locally at each C(α) effectively described by conformational angles resulting in Ramachandran plots. These, however, do not describe the conformations around hydrogen bonds, which can be non-local along the backbone and are of major importance for protein structure. Here, we introduce the spatial rotation between hydrogen bonded peptide planes as a new descriptor for protein structure locally around a hydrogen bond. Strikingly, this rotational descriptor sampled over high-quality structures from the protein data base (PDB) concentrates into 30 localized clusters, some of which correlate to the common secondary structures and others to more special motifs, yet generally providing a unifying systematic classification of local structure around protein hydrogen bonds. It further provides a uniform vocabulary for comparison of protein structure near hydrogen bonds even between bonds in different proteins without alignment.