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Rapid speciation and ecological divergence in the American seven-spined gobies (Gobiidae, Gobiosomatini) inferred from a molecular phylogeny.

The American seven-spined gobies (Gobiidae, Gobiosomatini) are highly diverse both in morphology and ecology with many endemics in the Caribbean region. We have reconstructed a molecular phylogeny of 54 Gobiosomatini taxa (65 individuals) based on a 1646-bp region that includes the mitochondrial 12S rRNA, tRNA-Val, and 16S rRNA genes. Our results support the monophyly of the seven-spined gobies and are in agreement with the existence of two major groups within the tribe, the Gobiosoma group and the Microgobius group. However, they reject the monophyly of some of the Gobiosomatini genera. We use the molecular phylogeny to study the dynamics of speciation in the Gobiosomatini by testing for departures from the constant speciation rate model. We observe a burst of speciation in the early evolutionary history of the group and a subsequent slowdown. Our results show a split among clades into coastal-estuarian, deep ocean, and tropical reef habitats. Major habitat shifts account for the early significant acceleration in lineage splitting and speciation rate and the initial divergence of the main Gobiosomatini clades. We found that subsequent diversification is triggered by behavior and niche specializations at least in the reef-associated clades. Overall, our results confirm that the diversity of Gobiosomatini has arisen during episodes of adaptive radiation, and emphasize the importance of ecology in marine speciation.

Adaptation, Biological↗

Population-genetic models of the fates of duplicate genes.

The ultimate fate of a duplicated gene is that it either silenced through inactivating mutations or both copies are maintained by selection. This later fate can occur via neofunctionalization wherein one copy acquires a new function or by subfunctionalization wherein the original function of the gene is partitioned across both copies. The relative probabilities of these three different fates involve often very subtle iterations between of population size, mutation rate, and selection. All three of these fates are critical to the expansion and diversification of gene families.

Evolution, Molecular↗

Diversification of the Wnt gene family on the ancestral lineage of vertebrates.

Diversification of the Wnt genes, a family of powerful developmental regulator molecules, is inferred by molecular evolutionary analyses. Fifty-five recently determined partial sequences from a variety of vertebrates and invertebrates, together with 17 published sequences, mostly from the mouse and Drosophila melanogaster, are analyzed. Wnt-1 through -7 originated before the last common ancestor of arthropods and deuterostomes lived. Another round of gene duplication, involving Wnt-3, -5, -7, and -10, occurred after the echinoderm lineage arose, on the ancestral lineage of jawed vertebrates. Increased constraints were imposed on the Wnt genes when jawed vertebrates originated, as indicated by an overall 4-fold lower rate of amino acid replacements in jawed vertebrates compared with invertebrates and jawless vertebrates. The Wnt genes are thus inferred to have undergone a disproportionately high amount of structural and functional evolution in the relatively short time (approximately 100 million years) between the origin of the echinoderm lineage and the first diversification of jawed vertebrates. A model is presented for the relationship of functional diversification of developmental regulators and their rates of amino acid replacement.

Amino Acid Sequence↗

Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica.

For 21 strains of Salmonella enterica, nucleotide sequences were obtained for three invasion genes, spaO, spaP, and spaQ, of the chromosomal inv/spa complex, the products of which form a protein export system required for entry of the bacteria into nonphagocytic host cells. These genes are present in all eight subspecies of the salmonellae, and homologues occur in a variety of other bacteria, including the enteric pathogens Shigella and Yersinia, in which they are plasmid borne. Evolutionary diversification of the invasion genes among the subspecies of S. enterica has been generally similar in pattern and average rate to that of housekeeping genes. However, the range of variation in evolutionary rate among the invasion genes is unusually large, and there is a relationship between the evolutionary rate and cellular location of the invasion proteins, possibly reflecting diversifying selection on exported proteins in adaptation to variable host factors in extracellular environments. The SpaO protein, which is hypervariable in S. enterica and exhibits only 24% sequence identity with its homologues in Shigella and Yersinia, is secreted. In contrast, the membrane-associated proteins SpaP, SpaQ, and InvA are weakly polymorphic and have > 60% sequence identity with the corresponding proteins of other enteric bacteria. Acquisition of the inv/spa genes may have been a key event in the evolution of the salmonellae as pathogens, following which the invention of flagellar phase shifting facilitated niche expansion to include warm-blooded vertebrates.

Adhesins, Bacterial↗

Highly constrained proteins contain an unexpectedly large number of amino acid tandem repeats.

Single-amino-acid tandem repeats are very common in mammalian proteins but their function and evolution are still poorly understood. Here we investigate how the variability and prevalence of amino acid repeats are related to the evolutionary constraints operating on the proteins. We find a significant positive correlation between repeat size difference and protein nonsynonymous substitution rate in human and mouse orthologous genes. This association is observed for all the common amino acid repeat types and indicates that rapid diversification of repeat structures, involving both trinucleotide slippage and nucleotide substitutions, preferentially occurs in proteins subject to low selective constraints. However, strikingly, we also observe a significant negative correlation between the number of repeats in a protein and the gene nonsynonymous substitution rate, particularly for glutamine, glycine, and alanine repeats. This implies that proteins subject to strong selective constraints tend to contain an unexpectedly high number of repeats, which tend to be well conserved between the two species. This is consistent with a role for selection in the maintenance of a significant number of repeats. Analysis of the codon structure of the sequences encoding the repeats shows that codon purity is associated with high repeat size interspecific variability. Interestingly, polyalanine and polyglutamine repeats associated with disease show very distinctive features regarding the degree of repeat conservation and the protein sequence selective constraints.

Amino Acid Sequence↗

Productivity in pharmaceutical-biotechnology R&D: the role of experience and alliances.

Using data on over 900 firms for the period 1988-2000, we estimate the effect on phase-specific biotech and pharmaceutical R&D success rates of a firm's overall experience, its experience in the relevant therapeutic category, the diversification of its experience across categories, the industry's experience in the category, and alliances with large and small firms. We find that success probabilities vary substantially across therapeutic categories and are negatively correlated with mean sales by category, which is consistent with a model of dynamic, competitive entry. Returns to experience are statistically significant but economically small for the relatively straightforward phase 1 trials. We find evidence of large, positive and diminishing returns to a firm's overall experience (across all therapeutic categories) for the larger and more complex late-stage trials that focus on a drug's efficacy. There is some evidence that a drug is more likely to complete phase 3 if developed by firms whose experience is focused rather than broad (diseconomies of scope). There is evidence of positive knowledge spillovers across firms for phase 1. However, for phase 2 and phase 3 the estimated effects of industry-wide experience are negative, which may reflect either higher Food and Drug Administration (FDA) approval standards in crowded therapeutic categories or that firms in such categories must pursue more difficult targets. Products developed in an alliance tend to have a higher probability of success, at least for the more complex phase 2 and phase 3 trials, and particularly if the licensee is a large firm.

Biotechnology↗

Evolutionary divergence of thyrotropin receptor structure.

The availability of 18 thyrotropin receptor (TSHR) sequences, including two recent entries for primates and seven from fish, have allowed us to investigate diversification of residues or domains during evolution. We used a likelihood ratio test for evolutionary rate shifts [Proc. Natl. Acad. Sci. 98 (2001) 14512] using LH/CGR sequences as an out-group. At each residue in the alignment, a statistical test was performed for a rate shift at the divergence between mammals and fish. Eighty-two rate shift sites were found, significantly more than was expected (p < 0.0001). The occurrence of rate shifts was highest in the intracellular tail, lowest in the transmembrane serpentine and intermediate in the ectodomain. In 52 mammalian sites, the rates were significantly faster than for the corresponding sites in fish. We have identified rate shift in sites important to TSHR function or in intimate proximity to such regions. The former category includes residues 53 and 55 (of LLR1 beta strand) and 253 and 255 (of LLR9 beta strand), crucial to TSH thyrotropic activity, residue 113, the site of N-linked glycosylation limited to humans, residue 310, an important switch in the hinge region for receptor binding and constitutive activity and residue 382 which centres a motif important for TSH-mediated receptor activation. The rate shifts positions close to functional region include a site proximal to a TSHR-specific motif on LLR3 beta strand, sites important in TM helix structure and homodimerization as well as, in the case of the third intracellular loop, to TSHR/G protein coupling. Rate shift analyses have identified residues whose manipulation in the human TSHR may lead to better understanding of receptor functions and help in the creation of designer analogues.

Amino Acid Sequence↗

Evolution of a VH gene family in low vertebrates.

Antibody genes represent one of the most complex receptor gene systems which have evolved in the vertebrate lineage. One of the central questions is how antibody variable region genes diversify the complementarity determining region (CDR) in evolution while they are subject to forces for sequence homogenization operating in multigene families. Information on germ line antibody genes in lower vertebrates is still fragmentary and it would be fruitful to gain insight into this question. We have studied the evolutionary stability of a rainbow trout VH family (RTVH 431) by Southern blot hybridization in various fish species. Comparison of our results with paleontological/zoological evidence suggests that this VH family has been preserved in the genomes of many fish species over a time span of 150 million years. We also show that there exist species-specific residues common to rainbow trout VH genes, which strongly supports the presence of genetic processes for homogenization. These results are compatible with the view that antibody V genes evolve at a fairly constant rate and that the homogenization process (e.g. gene duplication) may be slow enough to allow diversification of CDR by mutation, selection and drift.

Amino Acid Sequence↗

Dynamics of host plant use and species diversity in Polygonia butterflies (Nymphalidae).

The ability of insects to utilize different host plants has been suggested to be a dynamic and transient phase. During or after this phase, species can shift to novel host plants or respecialize on ancestral ones. Expanding the range of host plants might also be a factor leading to higher levels of net speciation rates. In this paper, we have studied the possible importance of host plant range for diversification in the genus Polygonia (Nymphalidae, Nymphalini). We have compared species richness between sistergroups in order to find out if there are any differences in number of species between clades including species that utilize only the ancestral host plants ('urticalean rosids') and their sisterclades with a broader (or in some cases potentially broader) host plant repertoire. Four comparisons could be made, and although these are not all phylogenetically or statistically independent, all showed clades including butterfly species using other or additional host plants than the urticalean rosids to be more species-rich than their sisterclade restricted to the ancestral host plants. These results are consistent with the theory that expansions in host plant range are involved in the process of diversification in butterflies and other phytophagous insects, in line with the general theory that plasticity may drive speciation.

Animals↗

Evolutionary relationships and systematics of the alphaviruses.

Partial E1 envelope glycoprotein gene sequences and complete structural polyprotein sequences were used to compare divergence and construct phylogenetic trees for the genus Alphavirus. Tree topologies indicated that the mosquito-borne alphaviruses could have arisen in either the Old or the New World, with at least two transoceanic introductions to account for their current distribution. The time frame for alphavirus diversification could not be estimated because maximum-likelihood analyses indicated that the nucleotide substitution rate varies considerably across sites within the genome. While most trees showed evolutionary relationships consistent with current antigenic complexes and species, several changes to the current classification are proposed. The recently identified fish alphaviruses salmon pancreas disease virus and sleeping disease virus appear to be variants or subtypes of a new alphavirus species. Southern elephant seal virus is also a new alphavirus distantly related to all of the others analyzed. Tonate virus and Venezuelan equine encephalitis virus strain 78V3531 also appear to be distinct alphavirus species based on genetic, antigenic, and ecological criteria. Trocara virus, isolated from mosquitoes in Brazil and Peru, also represents a new species and probably a new alphavirus complex.

3' Untranslated Regions↗

Analysis of the evolution in the management of endometrial cancer in Italy: a CTF study.

OBJECTIVE: In 1994 we mailed questionnaires to referral centers in Italy in order to evaluate the different opinions concerning aspects of endometrial cancer treatment, which is still controversial. The data processing showed a significant nonhomogeneity in disease management and prompted the Italian Society of Gynecologic Oncology to define guidelines for endometrial cancer adjuvant treatment. In 2001, we mailed again the same questionnaire to the same referral Centers in Italy. The aim of the second enquiry was the evaluation of changes in endometrial cancer management and the effective impact of the guidelines published. METHODS: The enquiry used the same questionnaires mailed in 1994; actually, we mailed those questionnaires to the same referral centers in Italy twice: in December 2000 and March 2001. The results of both the enquiries were collected in a relational data base, and the statistical evaluations were calculated using SPSS-statistics (Window ver. 8). RESULTS: Endometrial cancer treatment consists in abdominal hysterectomy and bilateral salpingo-oophorectomy. The unique relevant difference as to 1994 consists in the systemic performing of peritoneal cytology in endometrial cancer staging. Unlike the previous enquiry, adjuvant radiotherapy is not systematically performed in disease at stage Ic because of the substantial absence of confirmed data demonstrating a real benefit in terms of survival rate. The comparison between the two enquiries shows a significant change in medical planning and diversification attitude according to patient age and menopausal state. The disease management changes in patients over 75 years old, mainly with respect to surgery and primary therapy. CONCLUSIONS: We noted a resistance of many centers to accept some trends actually widespread in the literature but not yet performed in practical clinical.

Age Factors↗

The auxin gatekeepers: Evolution and diversification of the YUCCA family.

The critically important YUCCA (YUC) gene family is highly conserved and specific to the plant kingdom, primarily responsible for the final and rate-limiting step for indole-3-acetic acid (IAA) biosynthesis. IAA is an essential phytohormone, involved in virtually all aspects of plant growth and development. In addition, IAA is involved in fine-tuning plant responses to biotic and abiotic interactions and stresses. While the YUC gene family has significantly expanded throughout the plant kingdom, a detailed analysis of the evolutionary patterns driving this diversification has not been performed. Here, we present a comprehensive phylogenetic analysis of the YUC family, combining YUCs from species representing key evolutionary plant lineages. The evolutionary history of YUCs is complex and suggests multiple recruitment events via horizontal gene transfer from bacteria. We identify and hierarchically classify the YUC family into an early diverging grade, five distinct classes and 41 subclasses. Angiosperm YUC diversity and expansion are explained in the context of protein sequence conservation, as well as spatial and gene expression patterns. The presented YUC gene landscape offers new perspectives on the distribution and evolutionary trends of this crucial family, which facilitates further YUC characterization within plant development and response to environmental change.

Indoleacetic Acids↗

Positive selection and rates of evolution in immunodeficiency viruses from humans and chimpanzees.

Evolutionary theory predicts the recent spread of primate immunodeficiency viruses (PIVs) to new human populations to be accompanied by positive selection in response to new host environments and/or by random genetic drift. I assess evidence for positive selection in human and chimpanzee PIVs type I (PIV1s), using ratios of synonymous to nonsynonymous nucleotide change based on branch lengths and outgroup rooting. Ratios are smaller for PIV1s from humans than for PIV1 from a chimpanzee for the pol, gag, and env glycoprotein 120 (gp120) regions, indicating greater effects of positive selection in PIV1s from humans. Parsimony-based relative rate tests for amino acid changes showed significant differences between PIV1s from humans and chimpanzees in 18 of 48 pairwise comparisons, with all 18 showing faster rates of change in PIV1s from humans. This study indicates that in some instances, the recent evolution of human PIV1s follows a speciational pattern, in which increased diversification of taxa is correlated with greater amounts of character change appearing and being maintained through time. This extends the generality of the speciational pattern to a group of organisms (viruses) having the fastest known rates of anagenetic change for nucleotide characters and indicates that comprehensive understanding of PIV1 evolution requires consideration of both anagenetic change within viral lineages and the relative historical success of different viral clades. Phylogenetic analyses show that neither PIV1s infecting humans nor those infecting chimpanzees represent monophyletic groups and suggest multiple host-species shifts for PIV1s.

Animals↗

Identification of new TAP2 alleles in gorilla: evolution of the locus within hominoids.

Transporters associated with antigen processing molecules (TAP1 and TAP2) mediate the transfer of cytosolic peptides into the lumen of the endoplasmic reticulum for association with newly synthesized class I molecules of the major histocompatibility complex. Previous molecular and functional analyses of rat and human TAP2 homologues indicated major differences in gene diversification patterns and selectivity of peptides transported. Therefore, in this study, we analyzed the alleles of the gorilla TAP2 locus to determine whether the pattern of diversification resembled that in either of those two species. Sequence analysis of the TAP2 cDNAs from gorilla Epstein-Barr virus-transformed B-cell lines revealed four alleles with a genetic distance of less than 1%. The nucleotide substitutions distinguishing the alleles are confined to the 3' half of the coding region and occur individually or within two small clusters of variability. Diversification of the locus appears to have resulted from point substitutions and recombinational events. Evolutionary-rate estimates for the TAP2 gene in gorilla and human closely approximate those observed for other hominoid genes. The amino acid polymorphisms within the gorilla molecules are distinct from those in the human homologues. The absence of ancestral polymorphisms suggests that gorilla and human TAP2 genes have not evolved in a trans-species fashion but rather have diversified since the divergence of the lineages.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Antigenic variation and the murine immune response to Giardia lamblia.

The protozoan parasite Giardia lamblia is an important causative agent of acute or chronic diarrhoea in humans and various animals. During infection, the parasite survives the host's reactions by undergoing continuous antigenic variation of its major surface antigen, named VSP (variant surface protein). The VSPs form a unique family of cysteine-rich proteins that are extremely heterogeneous in size. The relevance of antigenic variation for the survival in the host has been most successfully studied by performing experimental infections in a combined mother/offspring mouse system and by using the G. lamblia clone GS/M-83-H7 (human isolate) as model parasite. In-vivo antigenic variation of G. lamblia clone GS/M-83-H7 is characterised by a diversification of the intestinal parasite population into a complex mixture of different variant antigen types. It could be shown that maternally transferred lactogenic anti-VSP IgA antibodies exhibit cytotoxic activity on the Giardia variant-specific trophozoites in suckling mice, and thus express a modulatory function on the proliferative parasite population characteristics. Complementarily, in-vitro as well as in-vivo experiments in adult animals indicated that non-immunological factors such as intestinal proteases may interfere into the process of antigen variation in that they favour proliferation of those variant antigen-type populations which resist the hostile physiological conditions within the intestine. These observations suggest that an interplay between immunological and physiological factors, rather than one of these two factor alone, modulates antigenic diversification of a G. lamblia population within an experimental murine host and thus influences the survival rate and strategy of the parasite.

Animals↗

Complex structural features of satellite DNA sequences in the genus Pimelia (Coleoptera: Tenebrionidae): random differential amplification from a common 'satellite DNA library'.

The major satellites of the nine species of the subgenera Pimelia s. str. and Amblyptera characterised in this paper are composed of longer monomers (500 and 700 bp) than those described previously in 26 Pimelia s. str. taxa (357 bp, a sequence called PIM357). Sequence analysis reveals partial similarity among these satellites and with the PIM357 monomers. The discrepancy between the phylogeny obtained based on three mitochondrial and two nuclear markers and that deduced from satellite DNA (stDNA) sequences suggests that the different Pimelia satellites were already present in a common ancestor forming what has been called a 'satellite DNA library'. Thus, the satellite profiles in the living species result from a random amplification of sequences from that 'library' during diversification of the species. However, species-specific turnover in the sequences has occurred at different rates. They have included abrupt replacements, a gradual divergence and, in other cases, no apparent change in sequence composition over a considerable evolutionary time. The results also suggest a common evolutionary origin of all these Pimelia satellite sequences, involving several rearrangements. We propose that the repeat unit of about 500 bp has originated from the insertion of a DNA fragment of 141 bp into the PIM357 unit. The 705-bp repeats have originated from a 32-bp direct duplication and the insertion of a 141-bp fragment in inverted orientation relative to a basic structure of 533 bp.

Animals↗

Lateral gene transfer: when will adolescence end?

The scope and impact of horizontal gene transfer (HGT) in Bacteria and Archaea has grown from a topic largely ignored by the microbiological community to a hot-button issue gaining staunch supporters (on particular points of view) at a seemingly ever-increasing rate. Opinions range from HGT being a phenomenon with minor impact on overall microbial evolution and diversification to HGT being so rampant as to obfuscate any opportunities for elucidating microbial evolution - especially organismal phylogeny - from sequence comparisons. This contentious issue has been fuelled by the influx of complete genome sequences, which has allowed for a more detailed examination of this question than previously afforded. We propose that the lack of common ground upon which to formulate consensus viewpoints probably stems from the absence of answers to four critical questions. If addressed, they could clarify concepts, reject tenuous speculation and solidify a robust foundation for the integration of HGT into a framework for long-term microbial evolution, regardless of the intellectual camp in which you reside. Here, we examine these issues, why their answers shape the outcome of this debate and the progress being made to address them.

Archaea↗

Mutation history of the roma/gypsies.

The 8-10 million European Roma/Gypsies are a founder population of common origins that has subsequently split into multiple socially divergent and geographically dispersed Gypsy groups. Unlike other founder populations, whose genealogy has been extensively documented, the demographic history of the Gypsies is not fully understood and, given the lack of written records, has to be inferred from current genetic data. In this study, we have used five disease loci harboring private Gypsy mutations to examine some missing historical parameters and current structure. We analyzed the frequency distribution of the five mutations in 832-1,363 unrelated controls, representing 14 Gypsy populations, and the diversification of chromosomal haplotypes in 501 members of affected families. Sharing of mutations and high carrier rates supported a strong founder effect, and the identity of the congenital myasthenia 1267delG mutation in Gypsy and Indian/Pakistani chromosomes provided the best evidence yet of the Indian origins of the Gypsies. However, dramatic differences in mutation frequencies and haplotype divergence and very limited haplotype sharing pointed to strong internal differentiation and characterized the Gypsies as a founder population comprising multiple subisolates. Using disease haplotype coalescence times at the different loci, we estimated that the entire Gypsy population was founded approximately 32-40 generations ago, with secondary and tertiary founder events occurring approximately 16-25 generations ago. The existence of multiple subisolates, with endogamy maintained to the present day, suggests a general approach to complex disorders in which initial gene mapping could be performed in large families from a single Gypsy group, whereas fine mapping would rely on the informed sampling of the divergent subisolates and searching for the shared genomic region that displays the strongest linkage disequilibrium with the disease.

Chromosome Mapping↗