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PubMed2004

Differential loss of ancestral gene families as a source of genomic divergence in animals.

A phylogenetic approach was used to reconstruct the pattern of an apparent loss of 2106 ancestral gene families in four animal genomes (Caenorhabditis elegans, Drosophila melanogaster, human and fugu). Substantially higher rates of loss of ancestral gene families were found in the invertebrates than in the vertebrates. These results indicate that the differential loss of ancestral gene families can be a significant factor in the evolutionary diversification of organisms.

Animals↗

PubMed2002

Evaluation of a population-based prevention program against influenza among Swiss elderly people.

INTRODUCTION: Influenza is a major cause of morbidity and mortality and occurs in epidemics in the winter. This study is an evaluation of a population-based prevention program against Influenza, implemented during autumn 2000 by the Health Department of the Canton of Vaud. METHODS: A pre-intervention/post-intervention design was used. In June 2000 and March 2001, 4007 questionnaires were sent to two different stratified random samples of people aged 65 and over living in the Canton of Vaud, Switzerland. Univariate, bivariate and multivariate analyses were performed. RESULTS: Vaccination coverage among people older than 65 was 58.0% in 1999 (95% CI: 56.2%-59.8%) and 58.4% (95% CI: 56.6%-60.2%) in 2000. A 6.5% significant increase in vaccination coverage was seen in the group of people aged 65 to 69 (p = 0.008). In the pre-intervention survey immunisation rates were 22.6% among people who had not consulted a physician, 59.2% among those who had consulted a physician once, and 73.2% among those who consulted twice or more (p = 0.001). These rates were respectively 30.8%, 58.0% and 75.1% (p = 0.001) in the post-intervention survey. CONCLUSIONS: No global increase in Influenza vaccination coverage in the elderly population could be observed following a community based intervention in a Swiss Canton. However, the enhanced vaccination rates noted in the 65-69 years old group and in people who did not receive medical care are compatible with an effect of the campaign. Further increase in vaccination coverage may be obtained by diversification and repetition of such promotion campaigns.

Age Factors↗

PubMed2002

Resistance to extinction of low fitness virus subjected to plaque-to-plaque transfers: diversification by mutation clustering.

Plaque-to-plaque transfers of RNA viruses lead to accumulation of mutations and fitness decrease. To test whether continuing plaque-to-plaque transfers would lead to viral extinction, we have subjected several low fitness foot-and-mouth disease virus (FMDV) clones to up to 130 successive plaque transfers, and have analyzed the evolution of plaque titers and genomic nucleotide sequences. No case of viral extinction could be documented. Some low fitness clones that posses an internal poly(A) tract evaded extinction by modifying the length or base composition of the poly(A) tract. The comparison of entire genomic sequences of FMDV clones at increasing plaque transfer number revealed that mutations accumulated at a uniform rate, and that they were distributed unevenly along the genome. Clusters of mutations were identified at different genomic sites in two plaque transfer lineages. Mutation clustering appears to occur stochastically and could not be related to fixation of compensatory mutations. The results document resistance of viral clones to extinction, and suggest that mutation clustering may be a mechanism of genetic diversification of low fitness virus.

Animals↗

PubMed1996

Continental breakup and the ordinal diversification of birds and mammals.

The classical hypothesis for the diversification of birds and mammals proposes that most of the orders diverged rapidly in adaptive radiations after the Cretaceous/Tertiary (K/T) extinction event 65 million years ago. Evidence is provided by the near-absence of fossils representing modern orders before the K/T boundary. However, fossil-based estimates of divergence time are known to be conservative because of sampling biases, and some molecular/time estimates point to earlier divergences among orders. In an attempt to resolve this controversy, we have estimated times of divergence among avian and mammalian orders with a comprehensive set of genes that exhibit a constant rate of substitution. Here we report molecular estimates of divergence times that average about 50-90% earlier than those predicted by the classical hypothesis, and show that the timing of these divergences coincides with the Mesozoic fragmentation of emergent land areas. This suggests that continental breakup may have been an important mechanism in the ordinal diversification of birds and mammals.

Animals↗

PubMed2006

Antibody repertoire development in the sheep.

The model of immunoglobulin (Ig) repertoire diversification in sheep has evolved dramatically in recent years. A process thought to involve the rearrangement of a very limited number of variable (V), diversity (D) and joining (J) segments followed by intense, antigen (Ag)-independent, somatic hypermutation is now known to be less recombinatorially restrictive and to involve fewer mutational events. Although mutation rates are now lower than previously thought, the somatic hypermutation process itself is no less critical to the development of the primary Ig repertoire in sheep. Recent studies have shown that those B cells that fail to mutate will die via apoptosis. Much of the V(D)J rearrangement is thought to occur in the fetal liver and spleen prior to development of the ileal Peyer's patch (PP) at approximately day 100 of gestation. Although de novo Ig rearrangement likely does not occur in the ileal PP, this tissue is a site of massive B-cell proliferation, selection and Ig diversification through somatic hypermutation.

Animals↗

PubMed1995

Variable region light chain genes encoding human antibodies to HIV-1.

In previous work, it was found that the heavy chain variable gene (VH) repertoire of human antibodies to HIV is markedly skewed and that the gp120 molecule is a ligand for VH3 gene products. Here, we have analysed the light chain (L-chain) variable region genes (VL) expressed by a panel of human monoclonal antibodies derived from an immunized volunteer, an AIDS patient and seropositive asymptomatic donors, and specific for HIV-1 p25, gp41 and gp120 proteins. We found that, in contrast to VH gene-family use, the VL repertoire does not exhibit a family-bias. We noticed however, a tendency to the use of VL genes that map to the downstream portion of the kappa locus. The VL genes expressed have mutated at lower rates than the corresponding VH genes and show no clustering of the replacement mutations in the hypervariable regions. We also found that the third hypervariable regions (CDR3) of the L-chains have undergone a marked diversification, with addition of untemplated nucleotides, frequent truncation at the 3' end of the VLs and somatic mutation. These molecular events result in a length heterogeneity of the CDR3s and an apparently positive selection of specific highly reactive amino acids. We conclude that the specificity of, at least some of the anti-HIV antibodies, is dictated by the L-chain CDR3 regions which bear the imprints of antigenic selection.

Amino Acid Sequence↗

PubMed1999

Mating systems of diploid and allotetraploid populations of tragopogon (Asteraceae). I. Natural populations

Although polyploidy is a significant force in the diversification of plants, the evolutionary consequences of polyploidization are not thoroughly understood. One possible consequence of polyploidy predicted by most population genetic theories is that the newly synthesized polyploid will self-fertilize at a greater rate than its diploid progenitors. To test for increased selfing rates in a polyploid, the mating systems of the allotetraploid Tragopogon mirus and one of its diploid progenitors, T. dubius, were compared. Tragopogon mirus is a recently derived species that arose sometime in the last 80 years and thus provides an opportunity to probe how quickly a shift in outcrossing rates might occur. Based on analyses of variation in maternal plants and their progeny arrays, the two tetraploid populations surveyed have higher outcrossing rates than the two diploid populations. This result is the opposite of that predicted by population genetic theory. This discrepancy between theoretical and empirical results may result from bias in the genetic sample, traits in the natural histories of the taxa involved or a lack of sufficient time since the formation of the polyploid (80 years or 40-80 generations) for a shift towards increased selfing to have occurred. Alternatively, the partial dominance model of inbreeding depression typically applied to polyploids may not be appropriate; the overdominance model predicts outcrossing rates in diploids and their tetraploid derivatives that are consistent with those observed in T. dubius and T. mirus.

Journal Article↗

PubMed2003

Exploring the boundary between pollination syndromes: bats and hummingbirds as pollinators of Burmeistera cyclostigmata and B. tenuiflora (Campanulaceae).

In this study I documented the degree of specialization in the pollination systems of Burmeistera cyclostigmata and B. tenuiflora (Campanulaceae) to explore the potential role of floral isolation in the diversification of the genus. I asked which floral characteristics are important in specializing on either bat or hummingbird pollination, and whether overlap between these floral syndromes can exist. I examined nocturnal and diurnal pollen deposition, pollinator visitation rates, and single visit effectiveness and related them to intra- and interspecific variation in Burmeistera floral characteristics at Monteverde, Costa Rica. Bats and hummingbirds visited both Burmeistera species, and bats pollinated both species. Owing to differences in floral morphology, however, hummingbirds effectively pollinated only B. tenuiflora. The generalized pollination system of B. tenuiflora demonstrates that there can be overlap in the boundary between ornithophily and chiropterophily, and that nectar production and timing of anthesis do not serve as barriers between these syndromes. The high intraspecific variation in floral color from green to red or purple did not correlate with either nocturnal or diurnal pollen deposition. Degree of flower accessibility did affect pollination; nocturnal pollen deposition significantly decreased as flowers become more obstructed. In Burmeistera, floral morphology and accessibility appear to be the most important floral characteristics for specialization at the boundary between ornithophily and chiropterophily.

Animals↗

PubMed1995

Structure and expression of clustered P element homologues in Drosophila subobscura and Drosophila guanche.

Sequence relationships and functional aspects were analysed in the P element homologues of Drosophila subobscura (Ds) and D. guanche (Dg). In both species, the P homologues are clustered at a single genomic position. They lack the characteristic terminal structures of actively transposing P elements, but they have the coding capacity for a 66-kDa 'repressor-like' protein. Two different types of cluster units (G-type and A-type) can be distinguished. The A-type unit, which is present in multiple copies, is transcribed in adult flies. In contrast, the G-type unit has a much lower copy number and is apparently not expressed. In Dg, the isolated G-type sequence carries a 420-bp insertion in the promoter region, which is probably responsible for inactivation. Sequence comparisons of different cluster units show that differentiation of the two types precedes the lineage split of these species. Substitution rates of the deduced proteins reveal two distinct subregions: high variability at the N terminus and strong sequence conservation in the rest of the protein. The variable region contains motifs characteristic of DNA-binding proteins. Adaptive diversification of the cluster units towards specific binding properties might be a plausible explanation for variability in the N-termini. Both unit types have lost the weak promoter region characteristic of P transposons. In the A-type unit, a new promoter has been formed which is apparently composed of parts of insertion sequences derived from two different mobile elements.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed2000

RPP13 is a simple locus in Arabidopsis thaliana for alleles that specify downy mildew resistance to different avirulence determinants in Peronospora parasitica.

Disease resistance (R) genes are found in plants as either simple (single allelic series) loci, or more frequently as complex loci of tandemly repeated genes. These different loci are likely to be under similar evolutionary forces from pathogens, but the contrast between them suggests important differences in mechanisms associated with DNA structure and recombination that generate and maintain R gene diversity. The RPP13 locus in Arabidopsis represents an important paradigm for studying the evolution of an R gene at a simple locus. The RPP13 allele from the accession Nd-1, designated RPP13-Nd, confers resistance to five different isolates of the biotrophic oomycete, Peronospora parasitica (causal agent of downy mildew), and encodes an NBS-LRR type R protein with a putative amino-terminal leucine zipper. The RPP13-Rld allele, cloned from the accession Rld-2, encodes a different specificity. Comparison of three RPP13 alleles revealed a high rate of amino acid divergence within the LRR domain, less than 80% identity overall, compared to the remainder of the protein (> 95% identity). We also found evidence for positive selection in the LRR domain for amino acid diversification outside the core conserved beta-strand/beta-turn motif, suggesting that more of the LRR structure is available for interaction with target molecules than has previously been reported for other R gene products. Furthermore, an amino acid sequence (LLRVLDL) identical in an LRR among RPP13 alleles is conserved in other LZ NBS-LRR type R proteins, suggesting functional significance.

Alleles↗

PubMed2007

Genome size evolution in relation to leaf strategy and metabolic rates revisited.

BACKGROUND AND AIMS: It has been proposed that having too much DNA may carry physiological consequences for plants. The strong correlation between DNA content, cell size and cell division rate could lead to predictable morphological variation in plants, including a negative relationship with leaf mass per unit area (LMA). In addition, the possible increased demand for resources in species with high DNA content may have downstream effects on maximal metabolic efficiency, including decreased metabolic rates. METHODS: Tests were made for genome size-dependent variation in LMA and metabolic rates (mass-based photosynthetic rate and dark respiration rate) using our own measurements and data from a plant functional trait database (Glopnet). These associations were tested using two metrics of genome size: bulk DNA amount (2C DNA) and monoploid genome size (1Cx DNA). The data were analysed using an evolutionary framework that included a regression analysis and independent contrasts using a phylogenetic tree with estimates of molecular diversification times. A contribution index for the LMA data set was also calculated to determine which divergences have the greatest influence on the relationship between genome size and LMA. KEY RESULTS AND CONCLUSIONS: A significant negative association was found between bulk DNA amount and LMA in angiosperms. This was primarily a result of influential divergences that may represent early shifts in growth form. However, divergences in bulk DNA amount were positively associated with divergences in LMA, suggesting that the relationship may be indirect and mediated through other traits directly related to genome size. There was a significant negative association between genome size and metabolic rates that was driven by a basal divergence between angiosperms and gymnosperms; no significant independent contrast results were found. Therefore, it is concluded that genome size-dependent constraints acting on metabolic efficiency may not exist within seed plants.

Evolution, Molecular↗

PubMed2002

Microevolutionary genomics of bacteria.

The availability of multiple complete genome sequences from the same species can facilitate attempts to systematically address basic questions in genome evolution. We refer to such efforts as "microevolutionary genomics". We report the results of comparative analyses of complete intraspecific genome (and proteome) sequences from four bacterial species--Chlamydophila pneumoniae, Escherichia coli, Helicobacter pylori and Neisseria meningitidis. Comparisons of average synonymous (K(s)) and nonsynonymous (K(a)) substitution rates were used to assess the influence of various biological factors on the rate of protein evolution. For example, E. coli experiences the most intense purifying selection of the species analyzed, and this may be due to the relatively larger population size of this species. In addition, essential genes were shown to be more evolutionarily conserved than nonessential genes in E. coli and duplicated genes have higher rates of evolution than unique genes for all species studied except C. pneumoniae. Different functional categories of genes were shown to evolve at significantly different rates emphasizing the role of category-specific functional constraints in determining evolutionary rates. Finally, functionally characterized genes tend to be conserved between strains, while uncharacterized genes are over-represented among the unique, strain-specific genes. This suggests the possibility that nonessential genes are responsible for driving the evolutionary diversification between strains.

Bacteria↗

PubMed2003

Directed evolution of retroviruses activatable by tumour-associated matrix metalloproteases.

Protease-activatable retroviral vectors offer the possibility of targeted gene transfer into cancer cells expressing a unique set of proteases as, for example, the matrix metalloproteases (MMPs). However, it is difficult to predict which substrate sequence will be optimally cleaved by a given tumour cell type. Therefore, we developed a novel approach that allows the selection of MMP-activatable retroviruses from libraries of viruses displaying combinatorially diversified protease substrates. Starting from a virus harbouring a standard MMP-2 substrate motif, after only two consecutive cycles of diversification and in vivo selection, MMP-activatable viruses were recovered. Biochemical characterization of the selected viruses revealed that their linker peptides showed a considerably increased sensitivity for MMP-2 cleavage, and interestingly also improved the particle incorporation rate of the Env protein. Owing to the optimized linker peptide, the selected viruses exhibited a greatly enhanced spreading efficiency through human fibrosarcoma cells, while having retained the dependency on MMP activation. Moreover, cell entry efficiency and virus titres were considerably improved as compared to the parental virus displaying the standard MMP-2 substrate. The results presented imply that retroviral protease substrate libraries allow the definition of MMP substrate specificities under in vivo conditions as well as the generation of optimally adapted tumour-specific viruses.

Cell Line↗

PubMed2002

Sympatric speciation by sexual conflict.

It is well established that sexual conflict can drive an endless coevolutionary chase between the sexes potentially leading to genetic divergence of isolated populations and allopatric speciation. We present a simple mathematical model that shows that sexual conflict over mating rate can result in two other general regimes. First, rather than "running away" from males, females can diversify genetically into separate groups, effectively "trapping" the males in the middle at a state characterized by reduced mating success. Female diversification brings coevolutionary chase to the end. Second, under certain conditions, males respond to female diversification by diversifying themselves. This response results in the formation of reproductively isolated clusters of genotypes that emerge sympatrically.

Adaptation, Physiological↗

PubMed2002

Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family of the MEINOX TALE homeodomain transcription factors.

TALE (three amino acid loop extension) homeodomain proteins include the PBC and the MEINOX sub-families. MEINOX proteins form heterodimer complexes with PBC proteins. Heterodimerization is crucial to DNA binding and for nuclear localization. PBC-MEINOX heterodimers bind DNA also in combination with HOX proteins, thereby modulating their DNA-binding specificity. TALE proteins therefore play crucial roles in multiple developmental and differentiation pathways in vivo. We report the identification and characterization of a novel human gene homologous to PREP1, called PREP2. Sequence comparisons indicate that PREP1 and PREP2 define a novel sub-family of MEINOX proteins, distinct from the MEIS sub-family. PREP2 is expressed in a variety of human adult tissues and displays a more restricted expression pattern than PREP1. PREP2 is capable of heterodimerizing with PBC proteins. Heterodimerization with PBX1 appears to be essential for nuclear localization of both PREP2 and PBX1. A comparison between the functional properties of PREP1 and PREP2 reveals that PREP2-PBX display a faster DNA-dissociation rate than PREP1-PBX heterodimers, suggesting different roles in controlling gene expression. Like PREP1, PREP2-PBX heterodimers are capable of forming ternary complexes with HOXB1. The analysis of some PREP2 in vitro properties suggests a functional diversification among PREP and between PREP and MEIS MEINOX proteins.

3T3 Cells↗

PubMed2004

Bifurcation into functional niches in adaptation.

One of the central questions in evolutionary biology concerns the dynamics of adaptation and diversification. This issue can be addressed experimentally if replicate populations adapting to identical environments can be investigated in detail. We have studied 501 such replicas using digital organisms adapting to at least two fundamentally different functional niches (survival strategies) present in the same environment: one in which fast replication is the way to live, and another where exploitation of the environment's complexity leads to complex organisms with longer life spans and smaller replication rates. While these two modes of survival are closely analogous to those expected to emerge in so-called r and K selection scenarios respectively, the bifurcation of evolutionary histories according to these functional niches occurs in identical environments, under identical selective pressures. We find that the branching occurs early, and leads to drastic phenotypic differences (in fitness, sequence length, and gestation time) that are permanent and irreversible. This study confirms an earlier experimental effort using microorganisms, in that diversification can be understood at least in part in terms of bifurcations on saddle points leading to peak shifts, as in the picture drawn by Sewall Wright.

Adaptation, Biological↗

PubMed2003

Phylogenetics of the grass genus Ehrharta: evidence for radiation in the summer-arid zone of the South African Cape.

Climatic and geological change may play a key role in stimulating biological radiations. Here, we use phylogenetic data to test whether the comparatively high diversity of ehrharteoid grasses in the Cape region of South Africa is the result of rapid radiation associated with the onset of a seasonally arid climate during the late Miocene. A phylogenetic hypothesis based on morphological and nucleotide sequence (nuclear ITS1 and plastid trnL-F) data confirms the monophyly of the African Ehrharta species and shows that the diversification of this lineage was centered in the Cape region. Sequence divergence data (ITS1 + trnL-F) indicate a pulse of rapid speciation, which may explain poor phylogenetic resolution within the African Ehrharta clade. Alternative calibrations yield a broad range of time estimates for the start and end of this radiation, most of which indicate a radiation inside the last 11 million years. A calibration based on the age of Ehrhartoideae suggests that radiation started 9.82 +/- 0.20 million years ago and ended 8.74 +/- 0.21 million years ago. Under alternative calibrations, estimated speciation rates during the period of radiation range between 0.87 and 4.18 species per million years. Parsimony optimization of habitat parameters reveals that radiation was correlated with the occupation of seasonally arid succulent karoo environments, wet heathy (fynbos) environments being ancestral. These data support earlier suggestions that late Miocene climatic change stimulated floristic radiation at the Cape, and highlight the potential importance of environmental change in powering diversification in continental floras.

Base Sequence↗

PubMed2004

The role of diversification in causing the correlates of dioecy.

Dioecy is reported to be correlated with a number of ecological traits, including tropical distribution, woody growth form, plain flowers, and fleshy fruits. Previous analyses have concentrated on determining whether dioecy is more likely to evolve in lineages possessing these traits, rather than considering the speciation and extinction rates of dioecious lineages with certain combinations of traits. To address the association between species richness in dioecious lineages as a function of the ecological traits, we compared the evolutionary success (i.e., relative species richness) of dioecious focal lineages with that of their nondioecious sister groups. This test was repeated for the evolutionary success of randomly chosen nondioecious lineages (control lineages) compared with their nondioecious sister groups. If the possession of certain ecological traits enhances the evolutionary success of dioecious lineages, we predict an association between the presence of these traits and relative species richness in the former, but not latter, set of sister-group comparisons. Dioecious focal lineages with a higher number of these traits experienced higher evolutionary success in sister-group comparisons, whereas no trend was found for the control focal lineages. The increase in evolutionary success was especially true for dioecious focal lineages that had a tropical distribution or fleshy fruit. We discuss how these results provide strong support for differential evolutionary success theories for the correlations between dioecy and the ecological traits considered.

Biodiversity↗