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Rapid evolution through gene duplication and subfunctionalization of the testes-specific alpha4 proteasome subunits in Drosophila.

Gene duplication is an important mechanism for acquiring new genes and creating genetic novelty in organisms. Evidence suggests that duplicated genes are retained at a much higher rate than originally thought and that functional divergence of gene copies is a major factor promoting their retention in the genome. We find that two Drosophila testes-specific alpha4 proteasome subunit genes (alpha4-t1 and alpha4-t2) have a higher polymorphism within species and are significantly more diverged between species than the somatic alpha4 gene. Our data suggest that following gene duplication, the alpha4-t1 gene experienced relaxed selective constraints, whereas the alpha4-t2 gene experienced positive selection acting on several codons. We report significant heterogeneity in evolutionary rates among all three paralogs at homologous codons, indicating that functional divergence has coincided with genic divergence. Reproductive subfunctionalization may allow for a more rapid evolution of reproductive traits and a greater specialization of testes function. Our data add to the increasing evidence that duplicated genes experience lower selective constraints and in some cases positive selection following duplication. Newly duplicated genes that are freer from selective constraints may provide a mechanism for developing new interactions and a pathway for the evolution of new genes.

Animals↗

Epigenetic silencing may aid evolution by gene duplication.

Gene duplication is commonly regarded as the main evolutionary path toward the gain of a new function. However, even with gene duplication, there is a loss-versus-gain dilemma: most newly born duplicates degrade to pseudogenes, since degenerative mutations are much more frequent than advantageous ones. Thus, something additional seems to be needed to shift the loss versus gain equilibrium toward functional divergence. We suggest that epigenetic silencing of duplicates might play this role in evolution. This study began when we noticed in a previous publication (Lynch M, Conery JS [2000] Science 291:1151-1155) that the frequency of functional young gene duplicates is higher in organisms that have cytosine methylation (H. sapiens, M. musculus, and A. thaliana) than in organisms that do not have methylated genomes (S. cerevisiae, D. melanogaster, and C. elegans). We find that genome data analysis confirms the likelihood of much more efficient functional divergence of gene duplicates in mammals and plants than in yeast, nematode, and fly. We have also extended the classic model of gene duplication, in which newly duplicated genes have exactly the same expression pattern, to the case when they are epigenetically silenced in a tissue- and/or developmental stage-complementary manner. This exposes each of the duplicates to negative selection, thus protecting from "pseudogenization." Our analysis indicates that this kind of silencing (i) enhances evolution of duplicated genes to new functions, particularly in small populations, (ii) is quite consistent with the subfunctionalization model when degenerative but complementary mutations affect different subfunctions of the gene, and (iii) furthermore, may actually cooperate with the DDC (duplication-degeneration-complementation) process.

Animals↗

Phytochrome-mediated development in land plants: red light sensing evolves to meet the challenges of changing light environments.

Phytochromes are photoreceptors that provide plants with circadian, seasonal, and positional information critical for the control of germination, seedling development, shade avoidance, reproduction, dormancy, and sleep movements. Phytochromes are unique among photoreceptors in their capacity to interconvert between a red-absorbing form (absorption maximum of approximately 660 nm) and a far-red absorbing form (absorption maximum of approximately 730 nm), which occur in a dynamic equilibrium within plant cells, corresponding to the proportions of red and far-red energy in ambient light. Because pigments in stems and leaves absorb wavelengths below about 700 nm, this provides plants with an elegant system for detecting their position relative to other plants, with which the plants compete for light. Certain aspects of phytochrome-mediated development outside of flowering plants are strikingly similar to those that have been characterized in Arabidopsis thaliana and other angiosperms. However, early diverging land plants have fewer distinct phytochrome gene lineages, suggesting that both diversification and subfunctionalization have been important in the evolution of the phytochrome gene family. There is evidence that subfunctionalization proceeded by the partitioning among paralogues of photosensory specificity, physiological response modes, and light-regulated gene expression and protein stability. Parallel events of duplication and functional divergence may have coincided with the evolution of canopy shade and the increasing complexity of the light environment. Within angiosperms, patterns of functional divergence are clade-specific and the roles of phytochromes in A. thaliana change across environments, attesting to the evolutionary flexibility and contemporaneous plasticity of phytochrome signalling in the control of development.

Arabidopsis↗

A class of eukaryotic GTPase with a punctate distribution suggesting multiple functional replacements of translation elongation factor 1alpha.

Translation elongation factor 1alpha (EF-1alpha, or EF-Tu in bacteria) is a highly conserved core component of the translation machinery that is shared by all cellular life. It is part of a large superfamily of GTPases that are involved in translation initiation, elongation, and termination, as well as several other cellular functions. Eukaryotic EF-1alpha (eEF-1alpha) is well studied and widely sampled and has been used extensively for phylogenetic analyses. It is generally thought that such highly conserved and functionally integrated proteins are unlikely to be involved in events such as lateral gene transfer or ancient duplication and gene sorting, which would undermine phylogenetic reconstruction. Here we describe a GTPase called EF-like (EFL), which is very similar to, but also distinct from, canonical eEF-1alpha. EFL is found in a wide variety of eukaryotes (dinoflagellates, haptophytes, cercozoa, green algae, choanoflagellates, and fungi), but its distribution is punctate: organisms that possess EFL are not closely related to one another, and EFL appears to be absent from the closest relatives of organisms that do possess it. Moreover, in most genomes where EFL is present, canonical eEF-1alpha appears to be absent. Analysis of functional divergence suggests that, whereas EFL is divergent in general, putative functional binding sites involved in translation are not significantly divergent as a whole. Altogether, it appears that EFL has replaced eEF-1alpha several times independently. This finding could be an indication of an ancient paralogy or, more likely, eukaryote-to-eukaryote lateral gene transfer.

Eukaryotic Cells↗

Complete mapping of divergent amino acids responsible for differential ligand binding of folate receptors alpha and beta.

The folate receptor (FR) type alpha may be distinguished from FR-beta by its higher affinity for the circulating folate coenzyme, (6S)-5-methyltetrahydrofolate (5-CH3H4folate), and its opposite stereospecificity for reduced folate coenzymes. Previous studies showed that a single leucine to alanine substitution at position 49 of the mature protein sequence is responsible for the functional divergence of FR-beta (Shen, F., Zheng, X., Wang, H., and Ratnam, M. (1997) Biochemistry 36, 6157-6163); however, the results also indicated that the minimum requirement for conversion of FR-beta to the functional equivalent of FR-alpha should include amino acid substitution(s) downstream of residue 92 in addition to mutation of L49A. To pinpoint those residues, chimeric FR-betaL49A/FR-alpha constructs including progressively shorter segments of FR-alpha downstream of position 92 as well as selected point mutants were studied. Simultaneous substitution of Leu-49, Phe-104, and Gly-166 in FR-beta with the corresponding FR-alpha residues Ala, Val, and Glu, respectively, reconstituted the ligand binding characteristics of FR-alpha. The results also exclude a role for other residues in FR-alpha in determining its functional divergence. A homology model of FR-alpha based on the three-dimensional structure of the chicken riboflavin-binding protein is used to show the position of residues 49, 104, and 166 in relation to the hydrophobic cleft corresponding to the riboflavin-binding pocket.

Amino Acid Sequence↗

[Divergent and convergent mechanisms of the integrative activity of the mammalian brain].

Convergent intercellular synaptic interaction is actualized, mainly, by two neurotransmitter systems: glutamate- and GABA-ergic (excitatory and inhibitory postsynaptic potentials, respectively). Fast and slow postsynaptic receptors of glutamate- and GABA-ergic synapses are described. All other brain systems are divergent neuromodulators. Modulators are released into the intercellular space and simultaneously interact with a large population of neurons. A hypothesis of divergent modulatory integration is described: the divergently functioning neuromodulators actualize stable functional states of the brain via appropriate long-term modification-inducing receptors. These stable states are a biochemical basis of the motivational and emotional states. Mechanisms of the secondary nuclear signaling triggered by the long-term modification-inducing receptors consolidate the stable states. The hypothesis of divergent modulatory integration is substantiated in the paper on the basis of the evidence obtained by the author and his collaborates. The haloperidol catalepsy and pentile-netetrazole kindling are considered as a behavioral model of the divergent modulatory integration. The experimental data suggest that divergently functioning neuromodulators actualize and consolidate general motivational and emotional states via the appropriate long-term modification-inducing receptors. The consolidation is structurally-specific. The motivational and emotional states concomitant of learning and memory are a specific variation of the general motivational and emotional state depending on the learning situation.

Animals↗

The elusive centromere: sequence divergence and functional conservation.

The centromere is an essential cis-acting structure present in the chromosomes of all eukaryotes, central to the mechanism that ensures proper segregation during meiosis and mitosis. Molecular characterization of centromeres in the budding and fission yeasts has advanced significantly over the last few years due to their relatively small size and the availability of functional assays. However, identification and characterization of centromeric sequences from multicellular organisms has proven to be slow and difficult in the absence of direct functional tests. Molecular data have recently become available on the centromere of Drosophila, making it possible to bridge a long-standing gap in our knowledge on the general structure of centromeres. An evaluation of the available data from yeast to man suggests that centromere sequence and centromere sequence organization have diverged significantly, even amongst different chromosomes of a single organism; however, overall centromere organization and kinetochore components might be significantly more conserved than thought previously.

Animals↗

Colonic lysozymes of rabbit (Japanese white): recent divergence and functional conversion.

Lysozyme was extracted from the feces of rabbit (Japanese White) with 2.5% acetic acid and purified by ion-exchange chromatography. Subsequent ion-exchange HPLC at pH 4.0 revealed the presence of two isozymes, namely rabbit colonic lysozymes 1 and 2. The amino acid sequences of these lysozymes were determined. The colonic lysozymes 1 and 2 showed 98% identity with each other and 94 and 95% identities with rabbit kidney lysozyme, respectively. The very high identities between kidney and colonic lysozymes indicate that the colonic isozymes diverged from the conventional kidney lysozyme very recently, probably after the divergence of rabbit from other rodents, accompanying the gene duplication. Despite the small changes in the sequences, the enzymatic properties of colonic lysozyme differ from those of the kidney lysozyme. The activity of the colonic lysozyme against Micrococcus luteus cells showed a narrow and acidic pH optimum, in contrast to the wide and high pH optimum of the kidney lysozyme. Changes in the enzymatic properties are analogous to those of the ruminant stomach lysozymes and may implicate adaptive evolution in the functional conversion of rabbit colonic lysozymes in gut.

Adaptation, Physiological↗

Genome-wide identification and expression profiling of the MADS-box gene family in Lavandula angustifolia.

BACKGROUND: MADS-box genes encode transcription factors critical for plant development, particularly floral organogenesis, flowering time regulation, and adaptation to environmental stresses. Among these, the MIKCC-type genes are pivotal regulators in floral developmental processes. Although the evolutionary diversification and functional dynamics of MADS-box genes have been extensively characterized in model plants such as Arabidopsis thaliana and Oryza sativa, their evolutionary relationships and functional profiles in Lavandula angustifolia, an economically significant aromatic plant, remain poorly understood. RESULTS: Genome-wide analysis identified 173 MADS-box genes in L. angustifolia, categorized into type I (Mα: 26; Mβ: 0; Mγ: 10) and type II (MIKCC: 125; MIKC*: 12) based on phylogenetic comparisons with A. thaliana. The MIKCC subgroup was further subdivided into 12 subclasses, including genes central to the ABCDE model of floral organ specification. Structural analyses revealed distinct conserved motifs and exon-intron configurations specific to each subgroup, indicative of functional divergence. Synteny analysis demonstrated Whole Genome Duplication (WGD) and segmental duplications as major contributors to MIKCC gene family expansion, notably among genes linked to floral organ development. Expression profiling via RNA-seq and quantitative real-time PCR (qPCR) showed type II MADS-box genes exhibited higher expression levels with pronounced tissue-specific and developmental stage-specific expression patterns compared to type I genes. Many type II genes displayed significant associations with floral organogenesis, floral transition, and abiotic stress responses, underscoring their essential roles in reproductive development and environmental adaptability in L. angustifolia. CONCLUSIONS: The identification and comprehensive characterization of 173 MADS-box genes in L. angustifolia highlight the significant expansion of the MIKCC subgroup driven primarily by WGD and segmental duplications. The distinct structural features and specific expression patterns observed provide insights into the functional divergence and complexity of these genes, particularly regarding floral organogenesis and adaptation to environmental stress. This study establishes a robust molecular basis for further functional analysis and genetic improvement of aromatic plants.

MADS Domain Proteins↗

Divergence of function in the thioredoxin fold suprafamily: evidence for evolution of peroxiredoxins from a thioredoxin-like ancestor.

The thioredoxin fold is found in proteins that serve a wide variety of functions. Among these are peroxiredoxins, which catalyze the reduction of hydrogen peroxide and alkyl peroxides. Although the common structural fold shared by thioredoxins and peroxiredoxins suggests the possibility that they have evolved from a common progenitor, it has been difficult to examine this hypothesis in depth because pairwise sequence identities between proteins in these two superfamilies are statistically insignificant. Using the Shotgun program, we have found that sequences of reductases involved in maturation of cytochromes in certain bacteria bridge the sequences of thioredoxins and peroxiredoxins. Analysis of motifs found in a divergent set of thioredoxins, cytochrome maturation proteins, and peroxiredoxins provides further support for an evolutionary relationship between these proteins. Within the conserved motifs are specific residues that are characteristic of individual protein classes, and therefore are likely to be involved in the specific functions of those classes. We have used this information, in combination with existing structural and functional information, to gain new insight into the structure-function relationships in these proteins and to construct a model for the emergence of peroxiredoxins from a thioredoxin-like ancestor.

Amino Acid Motifs↗

Evolution of complexity in motor patterns and jaw musculature of tetraodontiform fishes

The prey-processing behavior and jaw-adducting musculature of tetraodontiform fishes provide a novel system for studying the evolution of muscles and their function. The history of this clade has involved a pattern of repeated 'duplications' of jaw muscles by physical subdivision of pre-existing muscles. As a result, the number of adductor mandibulae muscles in different taxa varies from as few as two to as many as eight. We used electromyography (EMG) to quantify motor-pattern variation of adductor mandibulae muscles in four tetraodontiform species during feeding events on prey items that varied in durability and elusiveness. Statistical analyses of variation in EMG variables revealed significant differences in motor patterns between duplicated muscles derived from a common ancestral muscle in seven of nine cases examined. Overall individual EMG timing variables (e.g. relative onset or duration of bursts) were slightly less likely to diverge functionally than amplitude variables (e.g. relative intensity of bursts). Functional divergence was found in significant overall differences between muscles and twice as frequently in significant muscle-by-prey interaction terms. Such interactions represent an underappreciated way in which motor patterns can evolve and diversify. Regional variation was documented in undivided muscles in two species, indicating that it is possible for functional subdivision to precede anatomical subdivision. This study shows that phylogenetic increases in the number of tetraodontiform jaw adductor muscles have been associated with increases in the functional complexity of the jaws at the level of muscle activation patterns.

Journal Article↗

Nuclear monothiol glutaredoxins of Saccharomyces cerevisiae can function as mitochondrial glutaredoxins.

Glutaredoxins are thiol oxidoreductases that regulate protein redox state. In Saccharomyces cerevisiae, Grx1 and Grx2 are cytosolic dithiol glutaredoxins, whereas Grx3, Grx4, and Grx5 are monothiol glutaredoxins. Grx5 locates at the mitochondrial matrix and is needed for iron/sulfur cluster biogenesis. Its absence causes phenotypes such as inactivation of iron/sulfur enzymes and sensitivity to oxidative stress. Whereas Grx5 contains a single glutaredoxin domain, in Grx3 and Grx4 a thioredoxin-like domain is fused to the glutaredoxin domain. Here we have shown that Grx3 locates at the nucleus and that the thioredoxin-like domain is required for such location. We have addressed the functional divergence among glutaredoxins by targeting Grx2/3/4 molecules to the mitochondrial matrix using the Grx5 targeting sequence. The mitochondrial forms of Grx3 and Grx4 partially rescue the defects of a grx5 null mutant. On the contrary, mitochondrially targeted Grx2 does not suppress the mutant phenotype. Both the thioredoxin-like and glutaredoxin domains are needed for the mitochondrial activity of Grx3, although none of the cysteine residues at the thioredoxin-like domain is required for rescue of the grx5 phenotypes. We have concluded that dithiol glutaredoxins are functionally divergent from monothiol ones, but the latter can interchange their biological activities when compartment barriers are surpassed.

Aconitate Hydratase↗

Adaptive evolution in the Arabidopsis MADS-box gene family inferred from its complete resolved phylogeny.

Gene duplication is a substrate of evolution. However, the relative importance of positive selection versus relaxation of constraints in the functional divergence of gene copies is still under debate. Plant MADS-box genes encode transcriptional regulators key in various aspects of development and have undergone extensive duplications to form a large family. We recovered 104 MADS sequences from the Arabidopsis genome. Bayesian phylogenetic trees recover type II lineage as a monophyletic group and resolve a branching sequence of monophyletic groups within this lineage. The type I lineage is comprised of several divergent groups. However, contrasting gene structure and patterns of chromosomal distribution between type I and II sequences suggest that they had different evolutionary histories and support the placement of the root of the gene family between these two groups. Site-specific and site-branch analyses of positive Darwinian selection (PDS) suggest that different selection regimes could have affected the evolution of these lineages. We found evidence for PDS along the branch leading to flowering time genes that have a direct impact on plant fitness. Sites with high probabilities of having been under PDS were found in the MADS and K domains, suggesting that these played important roles in the acquisition of novel functions during MADS-box diversification. Detected sites are targets for further experimental analyses. We argue that adaptive changes in MADS-domain protein sequences have been important for their functional divergence, suggesting that changes within coding regions of transcriptional regulators have influenced phenotypic evolution of plants.

Arabidopsis↗

[Interaction of the brain mediator and modulator systems and their role in development of psychophysiological and psychopathological conditions].

Neuromodulators and neurotransmitters systems of brain were demarcated on the basis of their feature. The neurotransmitters ability to EPSP and IPSP generation were used for their indication. The neuromodulators divergent morphological feature and their ability to induce a slow intracellular metabotrope reaction were used for their indication. In this review fast and slow glutamate and GABA postsynaptic receptors are discussed. Modulators are released in the intercellular space and interact with a large population of neurons. The hypothesis of a divergent modulatory integration suggests that neuromodulators, functioning divergently actualize stable functional states of the brain via their own long-term modification-inducing receptors. These stable states form the biochemical basis of motivation and emotional states. The secondary nuclear signal mechanisms triggered by the long-term modification-inducing receptors act to consolidate these states. In this review, the authors experimental results are used to corroborate the hypothesis of divergent modulatory integration. Haloperidol catalepsy and pentylenetetrazole kindling and their interactions with learning processes are considered as a behavioral model of divergent modulatory integration.

Animals↗

Characterization of chemical allergens as a function of divergent cytokine secretion profiles induced in mice.

Allergic contact dermatitis (contact sensitivity) may be caused by a wide variety of chemicals. In addition, some chemical allergens may also induce respiratory sensitization. It has been demonstrated previously that topical exposure of mice to chemical contact and respiratory sensitizers stimulates divergent immune responses consistent with the selective activation of T helper 1 (Th1)- and Th2-type cells, respectively. Thus, exposure to trimellitic: anhydride (TMA) induces hapten-specific IgE antibody and a substantial increase in the total serum concentration of IgE. Conversely, oxazolone fails to provoke IgE production. In addition, lymph node cells (LNC) isolated following repeated topical exposure of mice to oxazolone or TMA display cytokine secretion profiles characteristic of Th1- and Th2-type cell stimulation. The purpose of the present investigations was to determine whether chemical allergens other than TMA and oxazolone, the respiratory allergen toluene diisocyanate (TDI) and the skin sensitizer dinitrofluorobenzene (DNFB), provoke differential cytokine expression. The production of the Th1-type product interferon gamma (IFN-gamma) and the Th2-type cytokines interleukins 4 and 10 (IL-4 and IL-10) by TDI- and DNFB-activated LNC has been measured. LNC derived from DNFB-exposed animals expressed substantial amounts of IFN-gamma, but only low levels of IL-10 and mitogen-inducible IL-4; exposure to TDI resulted in the converse profile of cytokine secretion. These data demonstrate that repeated topical administration of chemical allergen of different classes elicits in mice divergent cytokine secretion patterns consistent with the selective stimulation of distinct Th subsets. Analysis of such cytokine production profiles may permit in a single integrated assay the simultaneous identification and classification of chemical allergens.

Allergens↗

Functionality of divergence and convergence in a model of the insect olfactory system.

Recent studies have shown that the insect olfactory system uses a spatio-temporal encoding of odours in the population of projection neurons in the antennal lobe, and suggest that the information thus coded is spread across a large population of Kenyon cells in the mushroom bodies. At this stage, the temporal part of the code might be transformed into a spatial code, especially via the temporally sensitive mechanisms of paired-pulse facilitation and feedback inhibition with its possible associated rebound. We explore here a simple model of the olfactory system using a three-layer network of formal neurons, comprising a fixed number (three) of projection and inhibitory neurons, but a variable number of Kenyon cells. We show how enlarging the divergence of the network (i.e. the ratio between the number of Kenyon cells to the number of input - projection - neurons) alters the number of different output spatial states in response to a fixed set of spatio-temporal inputs, and may therefore improve its effectiveness in discriminating between these inputs. Such enlarged divergence also reduces the variation of this effectiveness among random realizations of the network connectivity. Our model shows that the discriminative effectiveness first increases with the divergence, and then plateaus for a divergence factor of approximately 20. The maximal average number of different outputs was 470.2, which was computed from some simulations with random realizations of connectivity and with a set of 512 possible inputs. The discriminative effectiveness of the network is sensitive to paired-pulse facilitation, and especially to inhibition with rebound.

Animals↗

Nucleotide sequence divergence and functional constraint in VIP precursor mRNA evolution between human and rat.

The nucleotide sequence analysis of cloned cDNA for VIP precursor from rat cerebral cortex reveals that the precursor contains both rat VIP and PHI-27. The deduced primary structure of rat VIP is identical with human VIP. The amino acid sequence of rat PHI-27 differs by 4 amino acids from human PHM-27. When each VIP precursor is divided functionally into 6 domains, the amino acid sequence homology between rat and human precursors ranges from 69 to 100%. In contrast, any domain exhibits an essentially equal degree of nucleotide sequence homology.

Amino Acid Sequence↗

Predicting outcome following pulmonary resection in cystic fibrosis patients.

A small subset of cystic fibrosis (CF) patients develop pulmonary disease primarily limited to one lobe or lung segment requiring prolonged recurrent hospitalizations with intensive medical therapy. Although surgery has been advocated for patients who do not respond to medical therapy, very little is known about criteria for selection of patients who might benefit from resection of the involved parenchyma. In an attempt to further define criteria for pulmonary resection in these patients, we retrospectively reviewed our experience at Tulane Medical Center over the past 10 years. Fourteen patients with CF, ranging from 3 to 30 years of age, underwent 17 pulmonary resections. Indications for surgery were persistent lobar or pulmonary atelectasis and bronchiectasis requiring multiple hospitalizations and unresponsive to medical therapy (n = 13), bronchopleural fistula (n = 2), or hemoptysis not responding to medical therapy or selective embolization (n = 2). Thirteen lobectomies and four pneumonectomies were performed. Only two resections were on the left side and 11 right upper lobectomies were performed. Postoperative hospitalization ranged from 5 to 21 days (mean, 8.5 days). Preoperative pulmonary function tests showed widely divergent function in these patients. Forced expiratory volume (FEV1) ranged from 11% to 88% whereas forced vital capacity (FVC) ranged from 20% to 100% of predicted values. Oxygen saturation ranged from 86% to 99%. Although there was no significant difference in preoperative and postoperative FVC or O2 saturation, there was a significant (P less than .003) decrease in the postoperative FEV1. In the 12 surviving patients followed for at least 1 year, there was also a significant reduction (P less than .001) in the number of hospitalizations required due to pulmonary exacerbations from an average 2.2 admissions per year (range, 0.44 to 3.5 admissions per year) to 1.1 admissions per year (range, 0 to 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗