Evolutionary transitions in protein fold space

With the number of known protein folds potentially approaching completion, the problems associated with their systematic classification are evaluated. It is argued that it will be difficult, if not impossible, to find a general metric based on pairwise comparison that will provide a satisfactory classification. It is suggested that some progress may be made through comparison against a library of idealised 'template' folds, but a proper solution can only be attained if this includes a model of the underlying evolutionary processes. These processes are considered with examples of some unexpected relationships among folds, including circular permutations. The problem is finally set in the wider context of the genetic environment, introducing complications relating to introns, gene fixation and population size.     

Evolutionary networks in the formatted protein sequence space.

In our recent work, a new approach to establish sequence relatedness, by walking through the protein sequence space, was introduced. The sequence space is built from 20 amino acid long fragments of proteins from a very large collection of fully sequenced prokaryotic genomes. The fragments, points in the space, are connected, if they are closely related (high sequence identity). The connected fragments form variety of networks of sequence kinship. In this research the networks in the formatted sequence space and their topology are analyzed. For lower identity thresholds a huge network of complex structure is formed, involving up to 10% points of the space. When the threshold is increased, the major network splits into a set of smaller clusters with a wide diversity of sizes and topologies. Such "evolutionary networks" may serve as a powerful sequence annotation tool that allows one to reveal fine details in the evolutionary history of proteins.     

A functional hierarchical organization of the protein sequence space

Background

It is a major challenge of computational biology to provide a comprehensive functional classification of all known proteins. Most existing methods seek recurrent patterns in known proteins based on manually-validated alignments of known protein families. Such methods can achieve high sensitivity, but are limited by the necessary manual labor. This makes our current view of the protein world incomplete and biased. This paper concerns ProtoNet, a automatic unsupervised global clustering system that generates a hierarchical tree of over 1,000,000 proteins, based solely on sequence similarity.

Results

In this paper we show that ProtoNet correctly captures functional and structural aspects of the protein world. Furthermore, a novel feature is an automatic procedure that reduces the tree to 12% its original size. This procedure utilizes only parameters intrinsic to the clustering process. Despite the substantial reduction in size, the system's predictive power concerning biological functions is hardly affected. We then carry out an automatic comparison with existing functional protein annotations. Consequently, 78% of the clusters in the compressed tree (5,300 clusters) get assigned a biological function with a high confidence. The clustering and compression processes are unsupervised, and robust.

Conclusions

We present an automatically generated unbiased method that provides a hierarchical classification of all currently known proteins.

     

Evolutionary innovations of squamate reproductive and developmental biology in the family Chamaeleonidae

The availability of molecular phylogenies has greatly accelerated our understanding of evolutionary innovations in the context of their origin and rate of evolution. Here, we assess the evolution of reproductive mode, developmental rate and body size in a group of squamate reptiles: the chameleons. Oviparity is ancestral and viviparity has evolved at least twice: Bradypodion and members of the Trioceros bitaeniatus clade are viviparous. Viviparous species are medium‐sized as a result of convergence from either small‐sized ancestors or large‐sized ancestors, respectively, but do not differ from oviparous species in clutch size, hatchling size or the trade‐off between clutch and hatchling size. Basal chameleons (Brookesia, Rhampholeon and Rieppeleon) are small‐sized and have developmental rates comparable with those of other lizards. Derived chameleons (Calumma, Chamaeleo, Trioceros and Furcifer) are mostly large‐sized and all have relatively slow developmental rates. Several clades of derived chameleons also exhibit developmental arrest (embryonic diapause or embryonic diapause plus cold torpor) and incubation periods extend to 6–10 months or more. Developmental arrest is associated with dry, highly seasonal climates in which the period favourable for oviposition and hatching is short. Long incubation periods thus ensure that hatching occurs during the favourable season following egg laying. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100 , 656–668.     

Evolutionary innovations in Antarctic brittle stars linked to glacial refugia

The drivers behind evolutionary innovations such as contrasting life histories and morphological change are central questions of evolutionary biology. However, the environmental and ecological contexts linked to evolutionary innovations are generally unclear. During the Pleistocene glacial cycles, grounded ice sheets expanded across the Southern Ocean continental shelf. Limited ice‐free areas remained, and fauna were isolated from other refugial populations. Survival in Southern Ocean refugia could present opportunities for ecological adaptation and evolutionary innovation. Here, we reconstructed the phylogeographic patterns of circum‐Antarctic brittle stars Ophionotus victoriae and O. hexactis with contrasting life histories (broadcasting vs brooding) and morphology (5 vs 6 arms). We examined the evolutionary relationship between the two species using cytochrome c oxidase subunit I (COI) data. COI data suggested that O. victoriae is a single species (rather than a species complex) and is closely related to O. hexactis (a separate species). Since their recent divergence in the mid‐Pleistocene, O. victoriae and O. hexactis likely persisted differently throughout glacial maxima, in deep‐sea and Antarctic island refugia, respectively. Genetic connectivity, within and between the Antarctic continental shelf and islands, was also observed and could be linked to the Antarctic Circumpolar Current and local oceanographic regimes. Signatures of a probable seascape corridor linking connectivity between the Scotia Sea and Prydz Bay are also highlighted. We suggest that survival in Antarctic island refugia was associated with increase in arm number and a switch from broadcast spawning to brooding in O. hexactis, and propose that it could be linked to environmental changes (such as salinity) associated with intensified interglacial‐glacial cycles.     

Evolutionary and polymorphic organization of the knotted1 homeobox in cereals

 Homeobox genes are the master control genes harbouring the homeobox which is crucial for developmental associated functions. One homeobox gene, knotted1, which has a role in leaf development, is conserved in plants and might have arisen from a single ancestral gene. Using PCR, we identified multiple kn1 homeoboxes in diverse cereals and showed a cereal/ species-specific organization correlating them to evolutionary changes. We postulate the insertion of a large intron preceded by duplication of the kn1 homeobox in the lineage leading to rice. Received: 17 October 1997 / Accepted: 9 December 1997     

Evolutionary innovations driving abiotic stress tolerance in C4 grasses and cereals

Grasslands dominate the terrestrial landscape, and grasses have evolved complex and elegant strategies to overcome abiotic stresses. The C₄ grasses are particularly stress tolerant and thrive in tropical and dry temperate ecosystems. Growing evidence suggests that the presence of C₄ photosynthesis alone is insufficient to account for drought resilience in grasses, pointing to other adaptations as contributing to tolerance traits. The majority of grasses from the Chloridoideae subfamily are tolerant to drought, salt, and desiccation, making this subfamily a hub of resilience. Here, we discuss the evolutionary innovations that make C₄ grasses so resilient, with a particular emphasis on grasses from the Chloridoideae (chloridoid) and Panicoideae (panicoid) subfamilies. We propose that a baseline level of resilience in chloridoid ancestors allowed them to colonize harsh habitats, and these environments drove selective pressure that enabled the repeated evolution of abiotic stress tolerance traits. Furthermore, we suggest that a lack of evolutionary access to stressful environments is partially responsible for the relatively poor stress resilience of major C₄ crops compared to their wild relatives. We propose that chloridoid crops and the subfamily more broadly represent an untapped reservoir for improving resilience to drought and other abiotic stresses in cereals.

Chloridoid grasses have evolved unique adaptations to adverse environments and represent an untapped reservoir for improving resilience to drought and other abiotic stresses in cereals.     

Evolutionary optimization in multimodal search space

Optimization by a simple evolution strategy based on a mutation and selection scheme without recombination was tested for its efficiency in multimodal search space. A modified Rastrigin function served as an objective function providing fitness landscapes with many local optima. It turned out that the evolutionary algorithm including adaptive stepsize control is wellsuited for optimization. The process is able to efficiently surmount local energy barriers and converge to the global optimum. The relation between the optimization time available and the optimal number of offspring was investigated and a simple rule proposed. Several numbers of offspring are nearly equally suited in a smooth search space, whereas in rough fitness landscapes an optimum is observed. In either case both very large and very small numbers of offspring turned out to be unfavourable for optimization.     

Funnel-like organization in sequence space determines the distributions of protein stability and folding rate preferred by evolution

To understand the physical and evolutionary determinants of protein folding, we map out the complete organization of thermodynamic and kinetic properties for protein sequences that share the same fold. The exhaustive nature of our study necessitates using simplified models of protein folding. We obtain a stability map and a folding rate map in sequence space. Comparison of the two maps reveals a common organizational principle: optimality decreases more or less uniformly with distance from the optimal sequence in the sequence space. This gives a funnel-shaped optimality surface. Evolutionary dynamics of a sequence population on these two maps reveal how the simple organization of sequence space affects the distributions of stability and folding rate preferred by evolution.     

Evolutionary innovations in the fossil record: the intersection of ecology, development, and macroevolution

The origins of evolutionary innovations have been intensively studied, but relatively little is known about their large-scale ecological patterns. For post-Paleozoic benthic marine invertebrates, which have the richest and most densely sampled fossil record, order-level taxa tend to appear first in onshore, disturbed habitats, even in groups that are now exclusively deep-water (so that present-day distributions are not reliable indicators of original environments). New results presented here show that the onshore-origination pattern is robust to shifts in taxonomic methods and to new paleontological discoveries, and the few available studies suggest that this pattern can also be seen in terms of excursions in morphospace or the acquisition of derived character states, without reference to taxonomic categories. The environmental pattern at high levels contrasts significantly with the origin of low-level novelties (such as defined genera and families) in crinoids, echinoids, and bryozoans, where first appearances tend to conform to their clade-specific bathymetric diversity gradients. This discordance seems to eliminate potential driving mechanisms that simply scale up within-population genetic or ecological processes. Little is known about the factors that promote the onshore-offshore expansion of orders across the continental shelf, or that drive some clades to abandon ancestral habitats for an exclusively deep-water distribution. The origin of evolutionary innovation must ultimately reside in developmental changes, but the onshore-origination bias could emerge from two different dynamics: the pattern could be primarily genetic and developmental, i.e., innovations truly arise onshore; or primarily ecological, i.e., innovations arise randomly but preferentially survive onshore. Whatever the ultimate driving mechanisms, these macroevolutionary patterns show that theories of large-scale evolutionary novelty must include an ecological dimension.     

Evolutionary perspectives on the links between mitochondrial genotype and disease phenotype

Background

Disorders of the mitochondrial respiratory chain are heterogeneous in their symptoms and underlying genetics. Simple links between candidate mutations and expression of disease phenotype typically do not exist. It thus remains unclear how the genetic variation in the mitochondrial genome contributes to the phenotypic expression of complex traits and disease phenotypes.

Scope of review

I summarize the basic genetic processes known to underpin mitochondrial disease. I highlight other plausible processes, drawn from the evolutionary biological literature, whose contribution to mitochondrial disease expression remains largely empirically unexplored. I highlight recent advances to the field, and discuss common-ground and -goals shared by researchers across medical and evolutionary domains.

Major conclusions

Mitochondrial genetic variance is linked to phenotypic variance across a variety of traits (e.g. reproductive function, life expectancy) fundamental to the upkeep of good health. Evolutionary theory predicts that mitochondrial genomes are destined to accumulate male-harming (but female-friendly) mutations, and this prediction has received proof-of-principle support. Furthermore, mitochondrial effects on the phenotype are typically manifested via interactions between mitochondrial and nuclear genes. Thus, whether a mitochondrial mutation is pathogenic in effect can depend on the nuclear genotype in which is it expressed.

General significance

Many disease phenotypes associated with OXPHOS malfunction might be determined by the outcomes of mitochondrial–nuclear interactions, and by the evolutionary forces that historically shaped mitochondrial DNA (mtDNA) sequences. Concepts and results drawn from the evolutionary sciences can have broad, but currently under-utilized, applicability to the medical sciences and provide new insights into understanding the complex genetics of mitochondrial disease. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.     

Evolutionary aspects of the genomic organization of rat chromosome 10

Using FISH and RH mapping a chromosomal map of rat chromosome 10 (RNO10) was constructed. Our mapping data were complemented by other published data and the final map was compared to maps of mouse and human chromosomes. RNO10 contained segments homologous to mouse chromosomes (MMU) 11, 16 and 17, with evolutionary breakpoints between the three segments situated in the proximal part of RNO10. Near one of these breakpoints (between MMU17 and 11) we found evidence for an inversion ancestral to the mouse that was not ancestral to the condition in the rat. Within each of the chromosome segments identified, the gene order appeared to be largely conserved. This conservation was particularly clear in the long MMU11-homologous segment. RNO10 also contained segments homologous to three human chromosomes (HSA5, 16, 17). However, within each segment of conserved synteny were signs of more extensive rearrangements. At least 13 different evolutionary breakpoints were indicated in the rat-human comparison. In contrast to what was found between rat and mouse, the rat-human evolutionary breaks were distributed along the entire length of RNO10.     

Caveolin-1 functions as a scaffolding protein for phosphofructokinase in the metabolic organization of vascular smooth muscle

Using confocal microscopy, we have demonstrated a similar distribution of phosphofructokinase (PFK) with caveolin-1 (CAV-1) mainly at the periphery (membrane) in freshly isolated vascular smooth muscle (VSM) cells and in cultured A7r5 VSM cells. Co-immunoprecipitation analysis validated the interaction between the proteins. To further test the hypothesis that PFK and CAV-1 are colocalized, we used small interfering RNA (siRNA) to downregulate CAV-1 expression and disrupt the protein-protein interactions between PFK and CAV-1. Transfection of cultured A7r5 cells with CAV-1 siRNA resulted in a decreased level of immunoreactive CAV-1 and a consequent shift in the distribution of PFK with less localization of PFK to the periphery of the cells and increased immunoreactivity at the perinuclear region as compared to control. Analysis of the average PFK intensity across cultured A7r5 cells demonstrated a higher central:peripheral intensity ratio (CPI ratio) in siRNA-treated cells than in the control. These results validate the possible role of CAV-1 as a scaffolding protein for PFK as evidenced by the significant redistribution of PFK after CAV-1 downregulation. We therefore conclude that CAV-1 may function as a scaffolding protein for PFK and that this contributes to the compartmentation of glycolysis from other metabolic pathways in VSM.     

ERM proteins in epithelial cell organization and functions

ERM (Ezrin, Radixin, Moesin) proteins are membrane-cytoskeleton linkers that regulate the structure and the function of specific domains of the plasma membrane. ERM proteins are expressed in all metazoan analyzed so far. Genetic analysis of ERM protein functions has recently been performed simultaneously in three different organisms, mouse, Drosophila melanogaster and C. elegans. These studies have revealed a remarkable conservation of the protein functions through evolution. Moreover they have shed light on the crucial role these proteins play in various physiological processes that occur in epithelial cells.     

Evolutionary origins and functions of the carotenoid biosynthetic pathway in marine diatoms

Carotenoids are produced by all photosynthetic organisms, where they play essential roles in light harvesting and photoprotection. The carotenoid biosynthetic pathway of diatoms is largely unstudied, but is of particular interest because these organisms have a very different evolutionary history with respect to the Plantae and are thought to be derived from an ancient secondary endosymbiosis between heterotrophic and autotrophic eukaryotes. Furthermore, diatoms have an additional xanthophyll-based cycle for dissipating excess light energy with respect to green algae and higher plants. To explore the origins and functions of the carotenoid pathway in diatoms we searched for genes encoding pathway components in the recently completed genome sequences of two marine diatoms. Consistent with the supplemental xanthophyll cycle in diatoms, we found more copies of the genes encoding violaxanthin de-epoxidase (VDE) and zeaxanthin epoxidase (ZEP) enzymes compared with other photosynthetic eukaryotes. However, the similarity of these enzymes with those of higher plants indicates that they had very probably diversified before the secondary endosymbiosis had occurred, implying that VDE and ZEP represent early eukaryotic innovations in the Plantae. Consequently, the diatom chromist lineage likely obtained all paralogues of ZEP and VDE genes during the process of secondary endosymbiosis by gene transfer from the nucleus of the algal endosymbiont to the host nucleus. Furthermore, the presence of a ZEP gene in Tetrahymena thermophila provides the first evidence for a secondary plastid gene encoded in a heterotrophic ciliate, providing support for the chromalveolate hypothesis. Protein domain structures and expression analyses in the pennate diatom Phaeodactylum tricornutum indicate diverse roles for the different ZEP and VDE isoforms and demonstrate that they are differentially regulated by light. These studies therefore reveal the ancient origins of several components of the carotenoid biosynthesis pathway in photosynthetic eukaryotes and provide information about how they have diversified and acquired new functions in the diatoms.     

Hematopoietic lineage cell-specific protein 1 functions in concert with the Wiskott-Aldrich syndrome protein to promote podosome array organization and chemotaxis in dendritic cells

Dendritic cells (DCs) are professional APCs that reside in peripheral tissues and survey the body for pathogens. Upon activation by inflammatory signals, DCs undergo a maturation process and migrate to lymphoid organs, where they present pathogen-derived Ags to T cells. DC migration depends on tight regulation of the actin cytoskeleton to permit rapid adaptation to environmental cues. We investigated the role of hematopoietic lineage cell-specific protein 1 (HS1), the hematopoietic homolog of cortactin, in regulating the actin cytoskeleton of murine DCs. HS1 localized to lamellipodial protrusions and podosomes, actin-rich structures associated with adhesion and migration. DCs from HS1(-/-) mice showed aberrant lamellipodial dynamics. Moreover, although these cells formed recognizable podosomes, their podosome arrays were loosely packed and improperly localized within the cell. HS1 interacts with Wiskott-Aldrich syndrome protein (WASp), another key actin-regulatory protein, through mutual binding to WASp-interacting protein. Comparative analysis of DCs deficient for HS1, WASp or both proteins revealed unique roles for these proteins in regulating podosomes with WASp being essential for podosome formation and with HS1 ensuring efficient array organization. WASp recruitment to podosome cores was independent of HS1, whereas HS1 recruitment required Src homology 3 domain-dependent interactions with the WASp/WASp-interacting protein heterodimer. In migration assays, the phenotypes of HS1- and WASp-deficient DCs were related, but distinct. WASp(-/y) DCs migrating in a chemokine gradient showed a large decrease in velocity and diminished directional persistence. In contrast, HS1(-/-) DCs migrated faster than wild-type cells, but directional persistence was significantly reduced. These studies show that HS1 functions in concert with WASp to fine-tune DC cytoarchitecture and direct cell migration.     

植物-微生物互惠共生: 演化机制与生态功能

植物-微生物互惠共生是一种特殊的合作形式, 在整个生命和陆地生态系统的演化历史中起着至关重要的作用。在全球环境变化背景下, 植物和微生物间的互惠共生对生态系统功能的维持具有重要意义。尽管合作/互惠共生如此重要, 在生物学中却存在着对它的历史偏见与忽视。特别地, 尽管互惠共生的理论与建模发展已有较长的历史, 但不同学科分支间仍存在着多种不同的观点。本综述从两个看似对立的视角概述植物-微生物互惠共生的概念框架, 即微生物学家关心的微观机制和生态系统生态学家关注的宏观影响。宏观模型通常从一组过于简单的假设出发, 便于理论分析。但微观机制是开展定量预测的基础, 因此新一代基于过程的宏观模型需嵌入微观机制, 这对预测全球变化下的生态系统响应至关重要。此外, 希望本文也可以吸引更多学者关注合作/互惠的重要作用, 并将这一概念应用于解决其他生态学和社会学问题。     

Nuclear genotype affects mitochondrial genome organization of CMS-S maize

Summary A WF9 strain of maize with the RD subtype of the S male-sterile cytoplasm (CMS-S) was converted to the inbred M825 nuclear background by recurrent backcrossing. The organization of the mitochondrial genomes of the F₁ and succeeding backcross progenies was analyzed and compared with the progenitor RD-WF9 using probes derived from the S1 and S2 mitochondrial episomes, and probes containing the genes for cytochrome c oxidase subunit I (coxI), cytochrome c oxidase subunit II (coxII) and apocytochrome b (cob). Changes in mitochondrial DNA (mtDNA) organization were observed for S1-, S2-, and coxI-homologous sequences that involve loss of homologous restriction enzyme fragments present in the RD-WF9 progenitor. With the coxI probe, the loss of certain fragments was accompanied by the appearance of a fragment not detectable in the progenitor. The changes observed indicate the effect of the nuclear genome on the differential replication of specific mitochondrial subgenomic entities.