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Divergent evolution within protein superfolds inferred from profile-based phylogenetics.

Many dissimilar protein sequences fold into similar structures. A central and persistent challenge facing protein structural analysis is the discrimination between homology and convergence for structurally similar domains that lack significant sequence similarity. Classic examples are the OB-fold and SH3 domains, both small, modular beta-barrel protein superfolds. The similarities among these domains have variously been attributed to common descent or to convergent evolution. Using a sequence profile-based phylogenetic technique, we analyzed all structurally characterized OB-fold, SH3, and PDZ domains with less than 40% mutual sequence identity. An all-against-all, profile-versus-profile analysis of these domains revealed many previously undetectable significant interrelationships. The matrices of scores were used to infer phylogenies based on our derivation of the relationships between sequence similarity E-values and evolutionary distances. The resulting clades of domains correlate remarkably well with biological function, as opposed to structural similarity, indicating that the functionally distinct sub-families within these superfolds are homologous. This method extends phylogenetics into the challenging "twilight zone" of sequence similarity, providing the first objective resolution of deep evolutionary relationships among distant protein families.

Evolution, Molecular↗

Neuropeptide binding reflects convergent and divergent evolution in species-typical group sizes.

Neuroendocrine factors that produce species differences in aggregation behavior ("sociality") are largely unknown, although relevant studies should yield important insights into mechanisms of affiliation and social evolution. We here focused on five species in the avian family Estrildidae that differ selectively in their species-typical group sizes (all species are monogamous and occupy similar habitats). These include two highly gregarious species that independently evolved coloniality; two territorial species that independently evolved territoriality; and an intermediate, modestly gregarious species that is a sympatric congener of one of the territorial species. Using males and females of each species, we examined binding sites for (125)I-vasoactive intestinal polypeptide (VIP), (125)I-sauvagine (SG; a ligand for corticotropin releasing factor, CRF, receptors) and a linear (125)I-V(1a) vasopressin antagonist (to localize receptors for vasotocin, VT). VIP, CRF and VT are neuropeptides that influence stress, anxiety and/or various social behaviors. For numerous areas (particularly within the septal complex), binding densities in the territorial species differed significantly from binding in the more gregarious species, and in most of these cases, binding densities for the moderately gregarious species were either comparable to the two colonial species or were intermediate to the territorial and colonial species. Such patterns were observed for (125)I-VIP binding in the medial bed nucleus of the stria terminalis, medial septum, septohippocampal septum, and subpallial zones of the lateral septum; for (125)I-SG binding in the infundibular hypothalamus, and lateral and medial divisions of the ventromedial hypothalamus; and for the linear (125)I-V(1a) antagonist in the medial septum, and the pallial and subpallial zones of the caudal lateral septum. With the exception of (125)I-SG binding in the infundibular hypothalamus, binding densitites are positively related to sociality.

Amphibian Proteins↗

Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley.

Flavone synthases (FNSs) catalyze the oxidation of flavanones to flavones, i.e. the formation of apigenin from (2S)-naringenin. While many plants express a microsomal-type FNS II, the soluble FNS I appears to be confined to a few species of the Apiaceae and was cloned recently from parsley plants. FNS I belongs to the Fe(II)/2-oxoglutarate-dependent dioxygenases characterized by short conserved sequence elements for cofactor binding, and its evolutionary context and mode of action are under investigation. Using a homology-based reverse transcription polymerase chain reaction approach, two additional flavonoid-specific dioxygenases were cloned from immature parsley leaflets, which were identified as flavanone 3beta-hydroxylase (FHT) and flavonol synthase (FLS) after expression in yeast cells. Sequence alignments revealed marginal differences among the parsley FNS I and FHT polypeptides of only 6%, while much less identity (about 29%) was observed with the parsley FLS. Analogous to FNS I, FLS oxidizes the flavonoid gamma-pyrone by introducing a C2, C3 double bond, and (2R,3S)-dihydrokaempferol (cis-dihydrokaempferol) was proposed recently as the most likely intermediate in both FNS I and FLS catalysis. Incubation of either FNS I or FLS with cis-dihydrokaempferol exclusively produced kaempferol and confirmed the assumption that flavonol formation occurs via hydroxylation at C3 followed by dehydratation. However, the lack of apigenin in these incubations ruled out cis-dihydrokaempferol as a free intermediate in FNS I catalysis. Furthermore, neither (+)-trans-dihydrokaempferol nor unnatural (-)-trans-dihydrokaempferol and 2-hydroxynaringenin served as a substrate for FNS I. Overall, the data suggest that FNS I has evolved uniquely in some Apiaceae as a paraphyletic gene from FHT, irrespective of the fact that FNS I and FLS catalyze equivalent desaturation reactions.

Amino Acid Sequence↗

Divergent evolution of part of the involucrin gene in the hominoids: unique intragenic duplications in the gorilla and human.

The gene for involucrin, an epidermal protein, has been remodeled in the higher primates. Most of the coding region of the human gene consists of a modern segment of repeats derived from a 10-codon sequence present in the ancestral segment of the gene. The modern segment can be divided into early, middle, and late regions. We report here the nucleotide sequence of three alleles of the gorilla involucrin gene. Each possesses a modern segment homologous to that of the human and consisting of 10-codon repeats. The early and middle regions are similar to the corresponding regions of the human allele and are nearly identical among the different gorilla alleles. The late region consists of recent duplications whose pattern is unique in each of the gorilla alleles and in the human allele. The early region is located in what is now the 3' third of the modern segment, and the late, polymorphic region is located in what is now the 5' third. Therefore, as the modern segment expanded during evolution, its 3' end became stabilized, and continuing duplications became confined to its 5' end. The expansion of the involucrin coding region, which began long before the separation of the gorilla and human, has continued in both species after their separation.

Animals↗

Premature cardiovascular mortality in France: divergent evolution between social categories from 1970 to 1990.

BACKGROUND: In France, differences in cardiovascular risk factor distribution have been observed which might be responsible for some disparities in cardiovascular mortality between social categories. The goal of the study was thus to assess the differences in coronary heart disease (CHD) and cerebrovascular diseases (CVD) mortality according to social category, and to determine their trends over the last 20 years in France. METHODS: Mortality data for CHD, CVD, diseases of the circulatory system (CS) and all causes mortality (TM) were based on death certificates for 1970, 1980 and 1990, and categorized by sex, age group (35-44 and 45-54 years), region and social category. RESULTS: Among active men, from 1970 to 1990, the overall decrease observed for all causes of death was significantly slower among employees and workers for CHD, CS and TM (P < 0.001), but not for CVD. In 1990, the highest mortality rates were observed among employees and workers for CHD, CVD and CS mortality. In women, no such trend was observed for CHD, CVD or CS mortality. No statistically significant difference between social categories was observed in 1990 for CHD and CVD. In the whole active population, a negative trend for the mortality rates was observed between 1970 and 1990 whatever the cause in both sexes. The ratio between mortality rates among non-active versus active people increased during the two decades in both sexes. CONCLUSIONS: In men, the inequalities have increased over the last two decades for CHD and have not been reduced for CVD. The category of employees and workers were found to be at special risk for premature cardiovascular disease mortality. Among women, the trends were less clear, although the tendencies were the same. An increasing disparity between active and non-active people suggests that a health-related selection process towards unemployment might have contributed to the decreasing mortality rates observed among employees and workers.

Adult↗

Eight new restriction endonucleases fröm Herpetosiphon giganteus--divergent evolution in a family of enzymes.

Characterization of eight restriction endonucleases isolated from five strains of Herpetosiphon giganteus is described. HgiCI from strain Hpg9 recognizes and cleaves the degenerate sequence: GGPyPuCC, producing 5'-hexanucleotide protruding ends. Endonucleases HgiBI, HgiCII and HgiEI are isoschizomers of AvaII; HgiCIII and HgiDII are isoschizomers of SalI; and HgiDI and HgiGI are isoschizomers of AcyI. Based upon their closely related and in part overlapping recognition specificities a close evolutionary relationship is proposed for all known Hgi restriction endonucleases.

Base Sequence↗

Divergent evolution during an experimental adaptive radiation.

How repeatable a process is evolution? Comparative studies of multicellular eukaryotes and experimental studies with unicellular prokaryotes document the repeated evolution of adaptive phenotypes during similar adaptive radiations, suggesting that the outcome of adaptive radiation is broadly reproducible. The goal of this study was to test this hypothesis by using phenotypic traits to infer the genetic basis of adaptation to simple carbon-limited environments in an extensive adaptive radiation. We used a clone of the bacterium Pseudomonas fluorescens to found two sets of experimental lines. The first set of lines was allowed to adapt to one of 23 novel environments for 1100 generations while the second set of lines was allowed to accumulate mutations by drift for 2000 generations. All lines were then assayed in the 95 environments provided by Biolog microplates to determine the phenotypic consequences of selection and drift. Replicate selection lines propagated in a common environment evolved similar adaptive components of their phenotype but showed extensive variation in non-adaptive phenotypic traits. This variation in non-adaptive phenotypic traits primarily resulted from the ascendance of different beneficial mutations in different lines. We argue that these results reconcile experimental and comparative approaches to studying adaptation by demonstrating that the convergent phenotypic evolution that occurs during adaptive radiation may be associated with radically different sets of beneficial mutations.

Adaptation, Biological↗

Two Paralogues as They Like It: Conserved and Divergent Evolution of Vertebrate Gcm Genes.

Gcm1 and Gcm2 are paralogous transcription factors in vertebrates that play key roles in the development of pharyngeal-derived epithelia, yet their deployment across vertebrate lineages remains incompletely understood. While Gcm2 shows deeply conserved pharyngeal expression across gnathostomes, Gcm1 has been mainly characterized in mammals, where it exhibits broader expression patterns. How Gcm1 is deployed in non-mammalian vertebrates has remained unexplored. Here, we performed a comparative analysis of Gcm1 expression in cartilaginous fishes, non-teleost actinopterygians, and amphibians. RNA in situ hybridization revealed conserved Gcm1 expression in gill epithelia across these taxa. Parallel analyses showed that Gcm2 is also expressed in gill epithelia, with overlapping but distinct spatial patterns. In addition, Gcm1 showed lineage-specific expression in bichir embryos, including strong expression in external gills and scattered epithelial cells in the yolk-sac membrane. In the external gills, Gcm1-positive cells possess vacuole-like cytoplasmic structures, suggesting a previously unrecognized epithelial cell population. Together, our findings indicate that Gcm1 and Gcm2 share ancestral expression in pharyngeal epithelia but have followed distinct evolutionary trajectories, with Gcm1 exhibiting greater lineage-specific diversification.

Animals↗

Divergent evolution of dispersal in a heterogeneous landscape.

The evolution of dispersal is investigated in a landscape of many patches with fluctuating carrying capacities and spatial heterogeneity in temporal fluctuations. Although asynchronous temporal fluctuations select for dispersal, spatial heterogeneity in the distribution of fluctuating environmental variables selects against it. We find evolutionary branching in dispersal rate leading to the evolutionarily stable coexistence of a high- and a low-dispersal phenotype. We study how the opposing forces of selection for and against dispersal change with the relative size and the environmental qualities of the source and sink habitats. Our results suggest that the evolution of dispersal dimorphism could be a first step towards speciation and local adaptation.

Animals↗

Polyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: single origin, divergent evolution, and multiple outcomes.

The development of models to investigate the pathobiology of premalignant breast lesions is a critical prerequisite for development of breast cancer prevention and early intervention strategies. Using tissue transplantation techniques, we modified the widely used polyomavirus middle T (PyV-mT) transgenic mouse model of breast cancer to study the premalignant stages of tumorigenesis. Premalignant atypical lesions were isolated from PyV-mT transgenic mice and used to generate two sets of three mammary intraepithelial neoplasia (MIN) outgrowth lines. Investigation of these six unique lines, each of which fulfills the criteria for MIN, has provided new information regarding the biology of PyV-mT-induced neoplasia. Although expression of the PyV-mT transgene was the primary initiating event for all lines, they exhibited different tumor latencies, metastatic potentials, and morphologies. Six distinguishable morphologic patterns of differentiation were identified within the premalignant outgrowths that are likely to represent several tumorigenic pathways. Further, several tumor phenotypes developed from each line and the tumors developing from the six lines had different metastatic potentials. These observations are consistent with the hypothesis that distinct pathways of PyV-mT-initiated neoplastic progression lead to different outcomes with respect to latency and metastasis. The MIN outgrowth lines share several characteristics with precursors of human breast cancer including the observation that gene expression profiles of tumors are more similar to those of the MIN outgrowth line outgrowth from which they developed than to other tumors. These lines provide an opportunity to study the full range of events occurring secondary to PyV-mT expression in the mammary gland.

Animals↗

Divergence and evolution of homologous regions of Bombyx mori nuclear polyhedrosis virus.

Homologous regions (hrs) (hr1,hr2-left,hr2-right,hr3,hr4-left,hr 4-right, and hr5) similar to those found in the Autographa californica nuclear polyhedrosis virus (AcNPV) genome were found in the Bombyx mori NPV (BmNPV) genome. The BmNPV hrs contained two to eight repeats of a homologous nucleotide sequence which were on average about 75 bp long. All of these homologous sequence repeats contained a 26-bp-long palindrome motif with an EcoRI or EcoRI-like site at its core. The consensus sequence of the BmNPV hrs showed 95% conservation with respect to those found in AcNPV. Nucleotide sequence analysis indicated that hr2-left and hr2-right of BmNPV evolved from an ancestor similar to hr2 of AcNPV by inversion, cleavage, and ligation. The polarities of the BmNPV and AcNPV hrs were conserved except for that of hr4-left. Within hr4-right of BmNPV, four repeats of a previously underscribed palindrome motif were found. Bmhr5D, a BmNPV mutant which lacked hr5, replicated at a rate similar to that of wild-type BmNPV in BmN cells and silkworm larvae, indicating that hr5 was not essential for viral replication. After ten passages of Bmhr5D in BmN cells, no detectable changes in its genome were observed by restriction endonuclease analysis. The evolution and divergence of the BmNPV genome are also discussed.

Animals↗

Evolution of gene families and relationship with organismal evolution: rapid divergence of tissue-specific genes in the early evolution of chordates.

To determine a possible relationship between organismal and molecular evolution, the divergence patterns of gene families were examined by taking special notice of functional difference, tissue distribution, and intracellular localization of the members. A phylogenetic analysis of 25 different gene families revealed interesting patterns of divergence of these families: Most gene duplications giving rise to different functions antedate the vertebrates-arthropods separation. On the other hand, in a group of members carrying virtually identical function to one another but differing in tissue distribution (tissue-specific isoform), most gene duplications have occurred independently in each of vertebrates and arthropods after the separation of the two animal groups. In family members encoding molecules localizing in cell compartments (compartmentalized isoforms), the gene duplications antedate the animals-fungi separation. In the cases of the Ca2+ pump and rab subfamilies, the compartmentalized isoforms were shown to have diverged during the early evolution of eukaryotes. A phylogenetic analysis of the tissue-specific isoforms from 26 different subfamilies revealed extensive gene duplications and rapid rates of amino acid substitutions in the early evolution of chordates before the separation of fishes and tetrapods. On the contrary, the genetic variations are relatively low in the later period. This pattern of evolution observed at the molecular level is correlated well with that of tissue evolution based on fossil evidence and morphological data, and thus evolution at the two levels may be related.

Animals↗

Genome Evolution of the Cyanobacterium Nostoc linckia under Sharp Microclimatic Divergence at "Evolution Canyon," Israel.

We describe the genomic DNA diversity and divergence of the cyanobacterium Nostoc linckia from "Evolution Canyon," a microsite consisting of ecologically contrasting slopes, south-facing slope (SFS) and north-facing slope (NFS), at lower Nahal Oren, Mt. Carmel, Israel. The opposing slopes share their limestone lithology but vary greatly in their ecology, primarily because of different levels of solar radiation (which is six times higher on the SFS than on the NFS). The warm and xeric SFS displays a tropical African savanna, whereas the cool and mesic NFS displays a temperate South European Mediterranean live-oak maquis shrub forest. The cyanobacterium Nostoc linckia tested here is a sessile microorganism, growing as a carpet on rock surfaces and constantly exposed to environmental fluctuations of solar radiation, temperature, and desiccation. We demonstrate remarkable interslope and intraslope genetic divergence of the genome (including both coding and noncoding regions) of Nostoc linckia, by using 211 AFLP (amplified fragment length polymorphism) DNA molecular marker loci. Genetic polymorphism of N. linckia subpopulations on the ecologically harsher SFS was significantly (p <0.05) higher (p = 99.53%) than was that of the subpopulations on the climatically milder nfs (p = 85.78%). genetic polymorphism (p) and gene diversity (he) were significantly correlated with variables influencing aridity stress: solar radiation (sr) (rp = 0.956; p = 0.046), temperature (tm) (rp = 0.993; p = 0.0068), and day-night temperature difference (tdd) (rp = 0.975; p = 0.025). as in other tested organisms from "evolution canyon", but even more exceptionally because of its completely sedentary nature, we suggest that the climatically stressed sfs environment is responsible for this marked increase of genetic polymorphism, which is maintained by the combined evolutionary forces of diversifying and balancing selection. This could highlight the importance of ecological stress and selection in evolution and its remarkable effect on the genetic system across the prokaryotic genome.

Journal Article↗