Evolution of ribonuclease H genes in prokaryotes to avoid inheritance of redundant genes

<p>Abstract</p> <p>Background</p> <p>A theoretical model of genetic redundancy has proposed that the fates of redundant genes depend on the degree of functional redundancy, and that functionally redundant genes will not be inherited together. However, no example of actual gene evolution has been reported that can be used to test this model. Here, we analyzed the molecular evolution of the ribonuclease H (RNase H) family in prokaryotes and used the results to examine the implications of functional redundancy for gene evolution.</p> <p>Results</p> <p>In prokaryotes, RNase H has been classified into RNase HI, HII, and HIII on the basis of amino acid sequences. Using 353 prokaryotic genomes, we identified the genes encoding the RNase H group and examined combinations of these genes in individual genomes. We found that the RNase H group may have evolved in such a way that the RNase HI and HIII genes will not coexist within a single genome – in other words, these genes are inherited in a mutually exclusive manner. Avoiding the simultaneous inheritance of the RNase HI and HIII genes is remarkable when RNase HI contains an additional non-RNase H domain, double-stranded RNA, and an RNA-DNA hybrid-binding domain, which is often observed in eukaryotic RNase H1. This evolutionary process may have resulted from functional redundancy of these genes, because the substrate preferences of RNase HI and RNase HIII are similar.</p> <p>Conclusion</p> <p>We provide two possible evolutionary models for RNase H genes in which functional redundancy contributes to the exclusion of redundant genes from the genome of a species. This is the first empirical study to show the effect of functional redundancy on changes in gene constitution during the course of evolution.</p

Degeneracy: a design principle for achieving robustness and evolvability

Robustness, the insensitivity of some of a biological system's functionalities to a set of distinct conditions, is intimately linked to fitness. Recent studies suggest that it may also play a vital role in enabling the evolution of species. Increasing robustness, so is proposed, can lead to the emergence of evolvability if evolution proceeds over a neutral network that extends far throughout the fitness landscape. Here, we show that the design principles used to achieve robustness dramatically influence whether robustness leads to evolvability. In simulation experiments, we find that purely redundant systems have remarkably low evolvability while degenerate, i.e. partially redundant, systems tend to be orders of magnitude more evolvable. Surprisingly, the magnitude of observed variation in evolvability can neither be explained by differences in the size nor the topology of the neutral networks. This suggests that degeneracy, a ubiquitous characteristic in biological systems, may be an important enabler of natural evolution. More generally, our study provides valuable new clues about the origin of innovations in complex adaptive systems.Comment: Accepted in the Journal of Theoretical Biology (Nov 2009

Modelling the evolution of transcription factor binding preferences in complex eukaryotes

Transcription factors (TFs) exert their regulatory action by binding to DNA with specific sequence preferences. However, different TFs can partially share their binding sequences due to their common evolutionary origin. This `redundancy' of binding defines a way of organizing TFs in `motif families' by grouping TFs with similar binding preferences. Since these ultimately define the TF target genes, the motif family organization entails information about the structure of transcriptional regulation as it has been shaped by evolution. Focusing on the human TF repertoire, we show that a one-parameter evolutionary model of the Birth-Death-Innovation type can explain the TF empirical ripartition in motif families, and allows to highlight the relevant evolutionary forces at the origin of this organization. Moreover, the model allows to pinpoint few deviations from the neutral scenario it assumes: three over-expanded families (including HOX and FOX genes), a set of `singleton' TFs for which duplication seems to be selected against, and a higher-than-average rate of diversification of the binding preferences of TFs with a Zinc Finger DNA binding domain. Finally, a comparison of the TF motif family organization in different eukaryotic species suggests an increase of redundancy of binding with organism complexity.Comment: 14 pages, 5 figures. Minor changes. Final version, accepted for publicatio

Dynamics of transcription factor binding site evolution

Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ~10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of "pre-sites" or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genetics.Comment: 28 pages, 15 figure

Neutral networks of genotypes: Evolution behind the curtain

Our understanding of the evolutionary process has gone a long way since the publication, 150 years ago, of "On the origin of species" by Charles R. Darwin. The XXth Century witnessed great efforts to embrace replication, mutation, and selection within the framework of a formal theory, able eventually to predict the dynamics and fate of evolving populations. However, a large body of empirical evidence collected over the last decades strongly suggests that some of the assumptions of those classical models necessitate a deep revision. The viability of organisms is not dependent on a unique and optimal genotype. The discovery of huge sets of genotypes (or neutral networks) yielding the same phenotype --in the last term the same organism--, reveals that, most likely, very different functional solutions can be found, accessed and fixed in a population through a low-cost exploration of the space of genomes. The 'evolution behind the curtain' may be the answer to some of the current puzzles that evolutionary theory faces, like the fast speciation process that is observed in the fossil record after very long stasis periods.Comment: 7 pages, 7 color figures, uses a modification of pnastwo.cls called pnastwo-modified.cls (included

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u