Speciation across the Tree of Life

Much of what we know about speciation comes from detailed studies of well-known model systems. Although there have been several important syntheses on speciation, few (if any) have explicitly compared speciation among major groups across the Tree of Life. Here, we synthesize and compare what is known about key aspects of speciation across taxa, including bacteria, protists, fungi, plants, and major animal groups. We focus on three main questions. Is allopatric speciation predominant across groups? How common is ecological divergence of sister species (a requirement for ecological speciation), and on what niche axes do species diverge in each group? What are the reproductive isolating barriers in each group? Our review suggests the following patterns. (i) Based on our survey and projected species numbers, the most frequent speciation process across the Tree of Life may be co-speciation between endosymbiotic bacteria and their insect hosts. (ii) Allopatric speciation appears to be present in all major groups, and may be the most common mode in both animals and plants, based on non-overlapping ranges of sister species. (iii) Full sympatry of sister species is also widespread, and may be more common in fungi than allopatry. (iv) Full sympatry of sister species is more common in some marine animals than in terrestrial and freshwater ones. (v) Ecological divergence of sister species is widespread in all groups, including ~70% of surveyed species pairs of plants and insects. (vi) Major axes of ecological divergence involve species interactions (e.g. host-switching) and habitat divergence. (vii) Prezygotic isolation appears to be generally more widespread and important than postzygotic isolation. (viii) Rates of diversification (and presumably speciation) are strikingly different across groups, with the fastest rates in plants, and successively slower rates in animals, fungi, and protists, with the slowest rates in prokaryotes. Overall, our study represents an initial step towards understanding general patterns in speciation across all organisms.     

Proteomics: A Paradigm Shift

ABSTRACT

Proteome—the protein complement of a genome—has become the protein renaissance and a key research tool in the post-genomic era. The basic technology involves the routine usage of gel electrophoresis and spectrometry procedures for deciphering the primary protein sequence/structure as well as knowing certain unique post-translational modifications that a particular protein has undergone to perform a specific function in the cell. However, the recent advancements in protein analysis have ushered this science to provide deeper, bigger and more valuable perspectives regarding performance of subtle protein-protein interactions. Applications of this branch of molecular biology are as vast as the subject is and include clinical diagnostics, pharmaceutical and biotechnological industries. The 21st century hails the use of products, procedures and advancements of this science as finer touches required for the grooming of fast-paced technology.     

Neuroproteomics: Expression Profiling of the Brain's Proteomes in Health and Disease

The term "proteome" describes the protein complement of a genome. Proteomes of cells are dynamic and are directly affected by environmental factors, such as stress and/or drug treatment, or as a result of aging and disease. One of the distinct advantages of proteomic analysis, not attainable with RNA expression data, is the ability to fractionate the cell's proteins into various subpopulations. In neuroscience, "neuromics" (proteomics in the central nervous system) is in its infancy, with a paucity of studies in the context of the brain. One of the objectives of this review is to illustrate the potential of neuromics to profile differences in the distribution of thousands of proteins as a function of disease markers. We have previously used this approach to determine the effects of varied postmortem interval in examining human brain tissue and to identify biomarkers. Here we review proteomic studies of schizophrenia, Alzheimer's disease, and Parkinson's disease. Experimental results regarding Parkinson's disease are presented to illustrate the potential of neuromics to identify pathways of pathogenesis and novel therapeutic targets.     

Proteomes reveal the lipid metabolic network in the complex plastid of Phaeodactylum tricornutum

Phaeodactylum tricornutum plastid is surrounded by four membranes, and its protein composition and function remain mysterious. In this study, the P. tricornutum plastid-enriched fraction was obtained and 2850 proteins were identified, including 92 plastid-encoded proteins, through label-free quantitative proteomic technology. Among them, 839 nuclear-encoded proteins were further determined to be plastidial proteins based on the BLAST alignments within Plant Proteome DataBase and subcellular localization prediction, in spite of the strong contamination by mitochondria-encoded proteins and putative plasma membrane proteins. According to our proteomic data, we reconstructed the metabolic pathways and highlighted the hybrid nature of this diatom plastid. Triacylglycerol (TAG) hydrolysis and glycolysis, as well as photosynthesis, glycan metabolism, and tocopherol and triterpene biosynthesis, occur in the plastid. In addition, the synthesis of long-chain acyl-CoAs, elongation, and desaturation of fatty acids (FAs), and synthesis of lipids including TAG are confined in the four-layered-membrane plastid based on the proteomic and GFP-fusion localization data. The whole process of generation of docosahexaenoic acid (22:6) from palmitic acid (16:0), via elongation and desaturation of FAs, occurs in the chloroplast endoplasmic reticulum membrane, the outermost membrane of the plastid. Desaturation that generates 16:4 from 16:0 occurs in the plastid stroma and outer envelope membrane. Quantitative analysis of glycerolipids between whole cells and isolated plastids shows similar composition, and the FA profile of TAG was not different. This study shows that the diatom plastid combines functions usually separated in photosynthetic eukaryotes, and differs from green alga and plant chloroplasts by undertaking the whole process of lipid biosynthesis.     

A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins

A previously developed computer program for protein design, RosettaDesign, was used to predict low free energy sequences for nine naturally occurring protein backbones. RosettaDesign had no knowledge of the naturally occurring sequences and on average 65% of the residues in the designed sequences differ from wild-type. Synthetic genes for ten completely redesigned proteins were generated, and the proteins were expressed, purified, and then characterized using circular dichroism, chemical and temperature denaturation and NMR experiments. Although high-resolution structures have not yet been determined, eight of these proteins appear to be folded and their circular dichroism spectra are similar to those of their wild-type counterparts. Six of the proteins have stabilities equal to or up to 7kcal/mol greater than their wild-type counterparts, and four of the proteins have NMR spectra consistent with a well-packed, rigid structure. These encouraging results indicate that the computational protein design methods can, with significant reliability, identify amino acid sequences compatible with a target protein backbone.     

Disulfide bonds and the stability of globular proteins.

An understanding of the forces that contribute to stability is pivotal in solving the protein-folding problem. Classical theory suggests that disulfide bonds stabilize proteins by reducing the entropy of the denatured state. More recent theories have attempted to expand this idea, suggesting that in addition to configurational entropic effects, enthalpic and native-state effects occur and cannot be neglected. Experimental thermodynamic evidence is examined from two sources: (1) the disruption of naturally occurring disulfides, and (2) the insertion of novel disulfides. The data confirm that enthalpic and native-state effects are often significant. The experimental changes in free energy are compared to those predicted by different theories. The differences between theory and experiment are large near 300 K and do not lend support to any of the current theories regarding the stabilization of proteins by disulfide bonds. This observation is a result of not only deficiencies in the theoretical models but also from difficulties in determining the effects of disulfide bonds on protein stability against the backdrop of numerous subtle stabilizing factors (in both the native and denatured states), which they may also affect.     

Thermodynamics of the Trp‐cage miniprotein unfolding in urea

The thermodynamic properties of unfolding of the Trp‐cage mini protein in the presence of various concentrations of urea have been characterized using temperature‐induced unfolding monitored by far‐UV circular dichroism spectroscopy. Analysis of the data using a two‐state model allowed the calculation of the Gibbs energy of unfolding at 25°C as a function of urea concentration. This in turn was analyzed by the linear extrapolation model that yielded the dependence of Gibbs energy on urea concentration, i.e. the m‐value for Trp‐cage unfolding. The m‐value obtained from the experimental data, as well as the experimental heat capacity change upon unfolding, were correlated with the structural parameters derived from the three dimensional structure of Trp‐cage. It is shown that the m‐value can be predicted well using a transfer model, while the heat capacity changes are in very good agreement with the empirical models based on model compounds studies. These results provide direct evidence that Trp‐cage, despite its small size, is an excellent model for studies of protein unfolding and provide thermodynamic data that can be used to compare with atomistic computer simulations. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

A simple covarion‐based approach to analyse nucleotide substitution rates

Using the ratio of nonsynonymous to synonymous nucleotide substitution rates (K_a/K_s) is a common approach for detecting positive selection. However, calculation of this ratio over a whole gene combines amino acid sites that may be under positive selection with those that are highly conserved. We introduce a new covarion‐based method to sample only the sites potentially under selective pressure. Using ancestral sequence reconstruction over a phylogenetic tree coupled with calculation of K_a/K_s ratios, positive selection is better detected by this simple covarion‐based approach than it is using a whole gene analysis or a windowing analysis. This is demonstrated on a synthetic dataset and is tested on primate leptin, which indicates a previously undetected round of positive selection in the branch leading to Gorilla gorilla.     

Thermodynamic stability of ecosystems

The stability of ecosystems during periods of stasis in their macro-evolutionary trajectory is studied from a non-equilibrium thermodynamic perspective. Individuals of the species are considered as units of entropy production and entropy exchange in an open thermodynamic system. Within the framework of the classical theory of irreversible thermodynamics, and under the condition of constant external constraints, such a system will naturally evolve toward a globally stable thermodynamic stationary state. It is thus suggested that the ecological steady state, or stasis, is a particular case of the thermodynamic stationary state, and that the evolution of community stability through natural selection is a manifestation of non-equilibrium thermodynamic directives. Furthermore, it is argued that punctuation of stasis leading to ecosystem succession, may be a manifestation of non-equilibrium "phase transitions" brought on by a change of external constraints through a thermodynamic critical point.     

蛋白质相互作用网络进化分析研究进展

近年来,随着高通量实验技术的发展和广泛应用,越来越多可利用的蛋白质相互作用网络数据开始出现．这些数据为进化研究提供了新的视角．从蛋白质、蛋白质相互作用、模体、模块直到整个网络五个层次,综述了近年来蛋白质相互作用网络进化研究领域的主要进展,侧重于探讨蛋白质相互作用、模体、模块直到整个网络对蛋白质进化的约束作用,以及蛋白质相互作用网络不同于随机网络特性的起源和进化等问题．总结了前人工作给学术界的启示,探讨了该领域未来可能的发展方向．     

Thermodynamic analysis of the effect of selective monodeamidation at asparagine 67 in ribonuclease A.

Selective deamidation of proteins and peptides is a reaction of great interest, both because it has a physiological role and because it can cause alteration in the biological activity, local folding, and overall stability of the protein. In order to evaluate the thermodynamic effects of this reaction in proteins, we investigated the temperature-induced denaturation of ribonuclease A derivatives in which asparagine 67 was selectively replaced by an aspartyl residue or an isoaspartyl residue, as a consequence of an in vitro deamidation reaction. Differential scanning calorimetry measurements were performed in the pH range 3.0-6.0, where the unfolding process is reversible, according to the reheating criterion used. It resulted that the monodeamidated forms have a different thermal stability with respect to the parent enzyme. In particular, the replacement of asparagine 67 with an isoaspartyl residue leads to a decrease of 6.3 degrees C of denaturation temperature and 65 kJ mol-1 of denaturation enthalpy at pH 5.0. These results are discussed and correlated to the X-ray three-dimensional structure of this derivative. The analysis leads to the conclusion that the difference in thermal stability between RNase A and (N67isoD)RNase A is due to enthalpic effects arising from the loss of two important hydrogen bonds in the loop containing residue 67, partially counterbalanced by entropic effects. Finally, the influence of cytidine-2'-monophosphate on the stability of the three ribonucleases at pH 5.0 is studied and explained in terms of its binding on the active site of ribonucleases. The analysis makes it possible to estimate the apparent binding constant and binding enthalpy for the three proteins.     

The heat capacity of proteins

The heat capacity plays a major role in the determination of the energetics of protein folding and molecular recognition. As such, a better understanding of this thermodynamic parameter and its structural origin will provide new insights for the development of better molecular design strategies. In this paper we have analyzed the absolute heat capacity of proteins in different conformations. The results of these studies indicate that three major terms account for the absolute heat capacity of a protein: (1) one term that depends only on the primary or covalent structure of a protein and contains contributions from vibrational frequencies arising from the stretching and bending modes of each valence bond and internal rotations; (2) a term that contains the contributions of noncovalent interactions arising from secondary and tertiary structure; and (3) a term that contains the contributions of hydration. For a typical globular protein in solution the bulk of the heat capacity at 25°C is given by the covalent structure term (close to 85% of the total). The hydration term contributes about 15 and 40% to the total heat capacity of the native and unfolded states, respectively. The contribution of non-covalent structure to the total heat capacity of the native state is positive but very small and does not amount to more than 3% at 25°C. The change in heat capacity upon unfolding is primarily given by the increase in the hydration term (about 95%) and to a much lesser extent by the loss of noncovalent interactions (up to ～5%). It is demonstrated that a single universal mathematical function can be used to represent the partial molar heat capacity of the native and unfolded states of proteins in solution. This function can be experimentally written in terms of the molecular weight, the polar and apolar solvent accessible surface areas, and the total area buried from the solvent. This unique function accurately predicts the different magnitude and temperature dependences of the heat capacity of both the native and unfolded states, and therefore of the heat capacity changes associated with folding/unfolding transitions. © 1995 Wiley-Liss, Inc.     

Molecular basis of cooperativity in protein folding. V. Thermodynamic and structural conditions for the stabilization of compact denatured states

The heat-denatured state of proteins has been usually assumed to be a fully hydrated random coil. It is now evident that under certain solvent conditions or after chemical or genetic modifications, the protein molecule may exhibit a hydrophobic core and residual secondary structure after thermal denaturation. This state of the protein has been called the “compact denatured” or “molten globule” state. Recently is has been shown that α-lactalbumin at pH < 5 denatures into a molten globule state upon increasing the temperature (Griko, Y., Freire, E., Privalov, P. L. Biochemistry 33:1889–1899, 1994). This state has a lower heat capacity and a higher enthalpy at low temperatures than the unfolded state. At those temperatures the stabilization of the molten globule state is of an entropic origin since the enthalpy contributes unfavorably to the Gibbs free energy. Since the molten globule is more structured than the unfolded state and, therefore, is expected to have a lower configurational entropy, the net entropic gain must originate primarily from solvent related entropy arising from the hydrophobic effect, and to a lesser extent from protonation or electrostatic effects. In this work, we have examined a large ensemble of partly folded states derived from the native structure of α-lactalbumin in order to identify those states that satisfy the energetic criteria of the molten globule. It was found that only few states satisfied the experimental constraints and that, furthermore, those states were part of the same structural family. In particular, the regions corresponding to the A, B, and C helices were found to be folded, while the β sheet and the D helix were found to be unfolded. At temperatures below 45°C the states exhibiting those structural characteristics are enthalpically higher than the unfolded state in agreement with the experimental data. Interestingly, those states have a heat capacity close to that observed for the acid pH compact denatured state of α-lactalbumin [980 cal (mol.K)^?l]. In addition, the folded regions of these states include those residues found to be highly protected by NMR hydrogen exchange experiments. This work represents an initial attempt to model the structural origin of the thermodynamic properties of partly folded states. The results suggest a number of structural features that are consistent with experimental data. © 1994 Wiley-Liss, Inc.     

Redesigning the hydrophobic core of a four-helix-bundle protein.

Rationally redesigned variants of the 4-helix-bundle protein Rop are described. The novel proteins have simplified, repacked, hydrophobic cores and yet reproduce the structure and native-like physical properties of the wild-type protein. The repacked proteins have been characterized thermodynamically and their equilibrium and kinetic thermal and chemical unfolding properties are compared with those of wild-type Rop. The equilibrium stability of the repacked proteins to thermal denaturation is enhanced relative to that of the wild-type protein. The rate of chemically induced folding and unfolding of wild-type Rop is extremely slow when compared with other small proteins. Interestingly, although the repacked proteins are more thermally stable than the wild type, their rates of chemically induced folding and unfolding are greatly increased in comparison to wild type. Perhaps as a consequence of this, their equilibrium stabilities to chemical denaturants are slightly reduced in comparison to the wild type.