Molecular Evolution across Mouse Spermatogenesis

Genes involved in spermatogenesis tend to evolve rapidly, but we lack a clear understanding of how protein sequences and patterns of gene expression evolve across this complex developmental process. We used fluorescence-activated cell sorting (FACS) to generate expression data for early (meiotic) and late (postmeiotic) cell types across 13 inbred strains of mice (Mus) spanning ∼7 My of evolution. We used these comparative developmental data to investigate the evolution of lineage-specific expression, protein-coding sequences, and expression levels. We found increased lineage specificity and more rapid protein-coding and expression divergence during late spermatogenesis, suggesting that signatures of rapid testis molecular evolution are punctuated across sperm development. Despite strong overall developmental parallels in these components of molecular evolution, protein and expression divergences were only weakly correlated across genes. We detected more rapid protein evolution on the X chromosome relative to the autosomes, whereas X-linked gene expression tended to be relatively more conserved likely reflecting chromosome-specific regulatory constraints. Using allele-specific FACS expression data from crosses between four strains, we found that the relative contributions of different regulatory mechanisms also differed between cell types. Genes showing cis-regulatory changes were more common late in spermatogenesis, and tended to be associated with larger differences in expression levels and greater expression divergence between species. In contrast, genes with trans-acting changes were more common early and tended to be more conserved across species. Our findings advance understanding of gene evolution across spermatogenesis and underscore the fundamental importance of developmental context in molecular evolutionary studies.     

Evolutionary rates vary among rRNA structural elements

Understanding patterns of rRNA evolution is critical for a number of fields, including structure prediction and phylogeny. The standard model of RNA evolution is that compensatory mutations in stems make up the bulk of the changes between homologous sequences, while unpaired regions are relatively homogeneous. We show that considerable heterogeneity exists in the relative rates of evolution of different secondary structure categories (stems, loops, bulges, etc.) within the rRNA, and that in eukaryotes, loops actually evolve much faster than stems. Both rates of evolution and abundance of different structural categories vary with distance from functionally important parts of the ribosome such as the tRNA path and the peptidyl transferase center. For example, fast-evolving residues are mainly found at the surface; stems are enriched at the subunit interface, and junctions near the peptidyl transferase center. However, different secondary structure categories evolve at different rates even when these effects are accounted for. The results demonstrate that relative rates and patterns of evolution are lineage specific, suggesting that phylogenetically and structurally specific models will improve evolutionary and structural predictions.     

Central nervous system and computation

Computational systems are useful in neuroscience in many ways. For instance, they may be used to construct maps of brain structure and activation, or to describe brain processes mathematically. Furthermore, they inspired a powerful theory of brain function, in which the brain is viewed as a system characterized by intrinsic computational activities or as a "computational information processor. "Although many neuroscientists believe that neural systems really perform computations, some are more cautious about computationalism or reject it. Thus, does the brain really compute? Answering this question requires getting clear on a definition of computation that is able to draw a line between physical systems that compute and systems that do not, so that we can discern on which side of the line the brain (or parts of it) could fall. In order to shed some light on the role of computational processes in brain function, available neurobiological data will be summarized from the standpoint of a recently proposed taxonomy of notions of computation, with the aim of identifying which brain processes can be considered computational. The emerging picture shows the brain as a very peculiar system, in which genuine computational features act in concert with noncomputational dynamical processes, leading to continuous self-organization and remodeling under the action of external stimuli from the environment and from the rest of the organism.     

Copulatory function and development shape modular architecture of genitalia differently in males and females

Genitalia are multitasking structures whose development is mediated by numerous regulatory pathways. This multifactorial nature provides an avenue for multiple sources of selection. As a result, genitalia tend to evolve as modular systems comprising semi-independent subsets of structures, yet the processes that give rise to those patterns are still poorly understood. Here, we ask what are the relative roles of development and function in shaping modular patterns of genitalia within populations and across species of stink-bugs. We found that male genitalia are less integrated, more modular, and primarily shaped by functional demands. In contrast, females show higher integration, lower modularity, and a predominant role of developmental processes. Further, interactions among parts of each sex are more determinant to modularity than those between the sexes, and patterns of modularity are equivalent between and within species. Our results strongly indicate that genitalia have been subjected to sex-specific selection, although male and female genitalia are homologous and functionally associated. Moreover, modular patterns are seemingly constant in the evolutionary history of stink-bugs, suggesting a scenario of multivariate stabilizing selection within each sex. Our study demonstrates that interactions among genital parts of the same sex may be more fundamental to genital evolution than previously thought.     

Hierarchical evolution of animal body plans

An open question in animal evolution is why the phylum- and superphylum-level body plans have changed so little, while the class- and family-level body plans have changed so greatly since the early Cambrian. Davidson and Erwin (Davidson and Erwin, 2006; Erwin and Davidson, 2009) proposed that the hierarchical structure of gene regulatory networks leads to different observed evolutionary rates for terminal properties of the body plan versus major aspects of body plan morphology. Here, we calculated the speed of evolution of genes in these gene regulatory networks. We found that the genes which determine the phylum and superphylum characters evolve slowly, while those genes which determine the classes, families, and speciation evolve more rapidly. This result furnishes genetic support to the hypothesis that the hierarchical structure of developmental regulatory networks provides an organizing structure which guides the evolution of aspects of the body plan.     

The molecular evolution of development

Morphological differences between species, from simple single-character differences to large-scale variation in body plans, can be traced to changes in the timing and location of developmental events. This has led to a growing interest in understanding the genetic basis behind the evolution of developmental systems. Molecular evolutionary genetics provides one of several approaches to dissecting the evolution of developmental systems, by allowing us to reconstruct the history of developmental genetic pathways, infer the origin and diversification of developmental gene functions, and assess the relative contributions of various evolutionary forces in shaping regulatory gene evolution. BioEssays 20 :700–711, 1998. © 1998 John Wiley & Sons, Inc.     

Evolution of Specificity in Protein-Protein Interactions

Hub proteins are proteins that maintain promiscuous molecular recognition. Because they are reported to play essential roles in cellular control, there has been a special interest in the study of their structural and functional properties, yet the mechanisms by which they evolve to maintain functional interactions are poorly understood. By combining biophysical simulations of coarse-grained proteins and analysis of proteins-complex crystallographic structures, we seek to elucidate those mechanisms. We focus on two types of hub proteins: Multi hubs, which interact with their partners through different interfaces, and Singlish hubs, which do so through a single interface. We show that loss of structural stability is required for the evolution of protein-protein-interaction (PPI) networks, and it is more profound in Singlish hub systems. In addition, different ratios of hydrophobic to electrostatic interfacial amino acids are shown to support distinct network topologies (i.e., Singlish and Multi systems), and therefore underlie a fundamental design principle of PPI in a crowded environment. We argue that the physical nature of hydrophobic and electrostatic interactions, in particular, their favoring of either same-type interactions (hydrophobic-hydrophobic), or opposite-type interactions (negatively-positively charged) plays a key role in maintaining the network topology while allowing the protein amino acid sequence to evolve.     

Evolution of Specificity in Protein-Protein Interactions

Hub proteins are proteins that maintain promiscuous molecular recognition. Because they are reported to play essential roles in cellular control, there has been a special interest in the study of their structural and functional properties, yet the mechanisms by which they evolve to maintain functional interactions are poorly understood. By combining biophysical simulations of coarse-grained proteins and analysis of proteins-complex crystallographic structures, we seek to elucidate those mechanisms. We focus on two types of hub proteins: Multi hubs, which interact with their partners through different interfaces, and Singlish hubs, which do so through a single interface. We show that loss of structural stability is required for the evolution of protein-protein-interaction (PPI) networks, and it is more profound in Singlish hub systems. In addition, different ratios of hydrophobic to electrostatic interfacial amino acids are shown to support distinct network topologies (i.e., Singlish and Multi systems), and therefore underlie a fundamental design principle of PPI in a crowded environment. We argue that the physical nature of hydrophobic and electrostatic interactions, in particular, their favoring of either same-type interactions (hydrophobic-hydrophobic), or opposite-type interactions (negatively-positively charged) plays a key role in maintaining the network topology while allowing the protein amino acid sequence to evolve.     

Perspectives on cardiac physiological ontogeny in crustaceans

Crustacean embryonic and larval systems offer a unique and valuable tool for furthering our understanding of both developmental processes and physiological regulatory mechanisms. The diverse array of developmental patterns exhibited by crustaceans allows species choice to be based on the specific questions being investigated, where defined larval forms are chosen based on their developmental pattern, degree of maturation or regulatory capabilities. However, this great diversity in developmental patterns, as well as crustacean diversity, can also confound ones ability to define or identify species for investigation. These issues are addressed and suggestions put forth to clarify some of the problems. The complexity and overlapping nature of adult cardio-regulatory systems makes teasing them apart difficult. Embryonic and larval systems exhibit varying degrees of regulatory complexity depending on developmental stage and ontogenetic pattern. This can allow complex adult regulatory systems to be teased apart temporally, as the developing animal builds regulatory pathways. Equally important is the nature of crustacean larvae; many undergo dramatic metamorphoses in cases where the larvae have adaptations to environments different to those of the adult. During environmental transitions physiological adaptations to immediate change should take precedence over long-term adult adaptations. It is therefore possible to look at physiological responses as a function of developmental/environmental adaptation, independent of adult functions.     

Regulatory punctuated equilibrium and convergence in the evolution of developmental pathways in direct-developing sea urchins

We made hybrid crosses between closely and distantly related sea urchin species to test two hypotheses about the evolution of gene regulatory systems in the evolution of ontogenetic pathways and larval form. The first hypothesis is that gene regulatory systems governing development evolve in a punctuational manner during periods of rapid morphological evolution but are relatively stable over long periods of slow morphological evolution. We compared hybrids between direct and indirect developers from closely and distantly related families. Hybrids between eggs of the direct developer Heliocidaris erythrogramma and sperm of the 4-million year distant species H. tuberculata, an indirect developer, restored feeding larval structures and paternal gene expression that were lost in the evolution of the direct-developing maternal parent. Hybrids resulting from the cross between eggs of H. erythrogramma and sperm of the 40-million year distant indirect-developer Pseudoboletia maculata are strikingly similar to hybrids between the congeneric hybrids. The marked similarities in ontogenetic trajectory and morphological outcome in crosses of involving either closely or distantly related indirect developing species indicates that their regulatory mechanisms interact with those of H. erythrogramma in the same way, supporting remarkable conservation of molecular control pathways among indirect developers. Second, we tested the hypothesis that convergent developmental pathways in independently evolved direct developers reflect convergence of the underlying regulatory systems. Crosses between two independently evolved direct-developing species from two 70-million year distant families, H. erythrogramma and Holopneustes purpurescens, produced harmoniously developing hybrid larvae that maintained the direct mode of development and did not exhibit any obvious restoration of indirect-developing features. These results are consistent with parallel evolution of direct-developing features in these two lineages.     

Long-term adaptation of epistatic genetic networks

Gene networks are likely to govern most traits in nature. Mutations at these genes often show functional epistatic interactions that lead to complex genetic architectures and variable fitness effects in different genetic backgrounds. Understanding how epistatic genetic systems evolve in nature remains one of the great challenges in evolutionary biology. Here we combine an analytical framework with individual-based simulations to generate novel predictions about long-term adaptation of epistatic networks. We find that relative to traits governed by independently evolving genes, adaptation with epistatic gene networks is often characterized by longer waiting times to selective sweeps, lower standing genetic variation, and larger fitness effects of adaptive mutations. This may cause epistatic networks to either adapt more slowly or more quickly relative to a nonepistatic system. Interestingly, epistatic networks may adapt faster even when epistatic effects of mutations are on average deleterious. Further, we study the evolution of epistatic properties of adaptive mutations in gene networks. Our results show that adaptive mutations with small fitness effects typically evolve positive synergistic interactions, whereas adaptive mutations with large fitness effects evolve positive synergistic and negative antagonistic interactions at approximately equal frequencies. These results provide testable predictions for adaptation of traits governed by epistatic networks and the evolution of epistasis within networks.     

Homology, Hox Genes, and Developmental Integration

The establishment and inheritance of individualized structuralunits is a key feature of morphological evolution, embodiedin the concept of homology. In current debates, homology isoften equated with identical genetic encoding. The empiricalevidence for this assumption is ambiguous. Genetic identitycan indicate morphological identity in some cases, but severalexamples show that gene expression patterns and regulatory systemsof development may be highly conserved while morphological charactersundergo dramatic evolutionary innovation. This indicates someindependence of structural homology from its genetic and developmentalmakeup. It is proposed that phenotypic evolution depends stronglyon the epigenetic context in which genetic redundancy becomesavailable for the control of new developmental interactions.The integrated character of developmental systems may representan important factor in the origin and identity of morphologicalcharacters and can stabilize incipient structures before theirfull genetic integration. The origin of the autopod sectionof the tetrapod limb is an example which suggests that novelhomologues can arise in evolution as a consequence of changingthe epigenetic context of conserved gene function.     

A simulation study of the genetic regulatory hierarchy for butterfly eyespot focus determination

The color patterns on the wings of butterflies have been an important model system in evolutionary developmental biology. Two types of models have been used to study these patterns. The first type of model employs computational techniques and generalized mechanisms of pattern formation to make predictions about how color patterns will vary as parameters of the model are changed. These generalized mechanisms include diffusion gradient, reaction-diffusion, lateral inhibition, and threshold responses. The second type of model uses known genetic interactions from Drosophila melanogaster and patterns of candidate gene expression in one of several butterfly species (most often Junonia (Precis) coenia or Bicyclus anynana) to propose specific genetic regulatory hierarchies that appear to be involved in color pattern formation. This study combines these two approaches using computational techniques to test proposed genetic regulatory hierarchies for the determination of butterfly eyespot foci (also known as border ocelli foci). Two computer programs, STELLA 8.1 and Delphi 2.0, were used to simulate the determination of eyespot foci. Both programs revealed weaknesses in a genetic model previously proposed for eyespot focus determination. On the basis of these simulations, we propose two revised models for eyespot focus determination and identify components of the genetic regulatory hierarchy that are particularly sensitive to changes in model parameter values. These components may play a key role in the evolution of butterfly eyespots. Simulations like these may be useful tools for the study of other evolutionary developmental model systems and reveal similar sensitive components of the relevant genetic regulatory hierarchies.