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Homologous recombination between different genotypes of hepatitis B virus.

Phylogenetic analysis was used to examine the evolutionary relationships among 99 complete HBV sequences. Analysis revealed nine viral genomes clustered with different genotypes depending on genome region analyzed. This discordance indicated that recombination events occurred during HBV history. The putative breakpoints between genomes of different genotypes have been mapped. Six mosaic genomes representing B/C hybrids were isolated in East Asia and three A/D hybrids in Italy. At least some recombinant strains appear to be fully viable and possess high evolutionary potential. As a result, B/C recombinants overspread through the East Asia region. They were found among the isolates from Japan, China and Indonesia. Our results suggest that recombination is a significant and relatively frequent event in the evolution of HBV genome. A possible mechanism and the implications of recombination for the natural history of HBV, clinically important properties, and phylogenetic reconstruction are discussed.

DNA, Viral↗

Comparison of papillomavirus and immunodeficiency virus evolutionary patterns in the context of a papillomavirus vaccine.

In contemplating a vaccine for human papillomaviruses (HPVs), it is important to consider the evolutionary context in which such a vaccine would be deployed. The human immunodeficiency virus, having been the subject of even more extensive study than HPV, shares certain salient features with regards to phylogenetic structure, and may serve as a model for contemplation of possible difficulties with HPV vaccination. However, there are also striking differences in the evolutionary potentials and histories of the viruses that permit an optimistic outlook for HPV. These similarities and differences, as well as their implications for vaccination studies, are reviewed.

Animals↗

Quantitative genetics in conservation biology.

Most of the major genetic concerns in conservation biology, including inbreeding depression, loss of evolutionary potential, genetic adaptation to captivity and outbreeding depression, involve quantitative genetics. Small population size leads to inbreeding and loss of genetic diversity and so increases extinction risk. Captive populations of endangered species are managed to maximize the retention of genetic diversity by minimizing kinship, with subsidiary efforts to minimize inbreeding. There is growing evidence that genetic adaptation to captivity is a major issue in the genetic management of captive populations of endangered species as it reduces reproductive fitness when captive populations are reintroduced into the wild. This problem is not currently addressed, but it can be alleviated by deliberately fragmenting captive populations, with occasional exchange of immigrants to avoid excessive inbreeding. The extent and importance of outbreeding depression is a matter of controversy. Currently, an extremely cautious approach is taken to mixing populations. However, this cannot continue if fragmented populations are to be adequately managed to minimize extinctions. Most genetic management recommendations for endangered species arise directly, or indirectly, from quantitative genetic considerations.

Animals↗

Migrational capacity of Fennoscandian populations of Venturia tremulae.

Genetic variation in three multiallelic loci was analysed with Temperature Gradient Gel Electrophoresis in order to assess the genetic population structure of Venturia tremulae var. tremulae in order to understand the evolutionary potential of the pathogen against resistance breeding. Also the identification of the fungus was verified with molecular analysis of reference isolates. The Fst and Gst values were very low indicating no substructuring or restrictions to gene flow between Fennoscandian populations of V. tremulae. The results imply high epidemiological efficiency of the fungus and therefore continuous breeding programme should be implemented for Venturia resistance of aspen.

Ascomycota↗

Genetic variation, occurrence of mating types and different forms of Pyrenophora teres causing net blotch of barley in Finland.

The amplified fragment length polymorphism (AFLP) was used to study genetic variation in Pyrenophora teres causing net blotch of barley in Finland. The mean similarity was 93% between all isolates and a bit higher within two distinct populations based on 175 AFLP markers. Despite the high genetic similarity, 70 unique AFLP genotypes were identified among 72 isolates. Most of the genetic variation (68.5%) was observed within a field population and a smaller portion (30.3%) between them. Significant genetic differentiation (Fst = 0.308, P < 0.001) was identified between field populations. However only 1.2% of the variation was observed between mating types within a field and a lack of genetic differentiation (Fsc = 0.017, P = 0.087) was observed. The occurrence of the form of blotch (spot type, f. sp. maculata, or net type, P. teres f. sp. teres) was identified with specific PCR. All isolates were found to be of the net type. The existence of both mating types (MAT1 and MAT2) was identified for the first time in Finland and the ratio of the two mating types was almost 1:1 in both locations. The evolutionary potential and the possibility of sexual reproduction of P. teres occurring in Finland are discussed.

Ascomycota↗

The C-terminal half of the anti-sigma factor FlgM contains a dynamic equilibrium solution structure favoring helical conformations.

FlgM is the inhibitor of sigma 28, a transcription factor specific for the expression of bacterial flagella and chemotaxis genes. FlgM is also exported from the cytoplasm to the outside of the cell during the process of flagella filament assembly. In the absence of its targets, FlgM is a dynamic, mostly unfolded, molecule [Daughdrill, G. W., et al. (1997) Nat. Struct. Biol. 4(4), 285-291]. The NMR resonance assignments, dynamics, and average secondary structure of this mostly unfolded form of FlgM are reported here. Because of the dynamic behavior of FlgM, the deviation of C alpha chemical shifts from the random coil values was used to test for the presence of secondary structure [Wishart, D. S., and Sykes, B. D. (1994) Methods Enzymol. 239, 363-392]. This analysis shows two contiguous regions in the C-terminal half of FlgM with helical C alpha chemical shifts. These two regions, M60-G73 and A83-A90, contained less than 10 medium-range NOEs, and the 15N relaxation parameters suggest the helical structure is not rigid. However, the C alpha chemical shifts of M60-G73, A83-A90, and other residues in the C-terminal half of FlgM shift toward their canonical random coil values with the addition of a chemical denaturant. Along with the values of the order parameter, S2, this observation suggests the C-terminal half of FlgM exists in an equilibrium structural state that is nonrandom. The same analysis of the N-terminal half of FlgM suggests it more closely resembles a random coil in conditions with and without denaturant. It appears the C-terminal half of FlgM lacks sufficient intramolecular contacts to form stable secondary or tertiary structures. It is known this C-terminal region becomes rigidly held when FlgM binds sigma 28 (Daughdrill et al., 1997), and it is possible that binding stabilizes the helical structure. The potential evolutionary relationship between the inhibitory interaction of FlgM with sigma 28 and the autoinhibition observed in sigma 70 is discussed.

Bacterial Proteins↗

Evolution in action through hybridisation and polyploidy in an Iberian freshwater fish: a genetic review.

The Iberian minnow Leuciscus alburnoides represents a complex of diploid and polyploid forms with altered modes of reproduction. In the present paper, we review the recent data on the origin, reproductive modes, and inter-relationships of the various forms of the complex, in order to predict its evolutionary potential. The complex follows the hybrid-origin model suggested for most other asexual vertebrates. Diploid and triploid females from the southern river basins exhibit reproductive modes that cannot be conveniently placed into the categories generally recognised for these vertebrate complexes, which imply continuous shifting between forms, where genomes derived from both parental ancestors are cyclically lost, gained or replaced. Replacement of nuclear genomes allow the introduction of novel genetic material, that may compensate for the disadvantages of asexual reproduction. Contrasting with most other vertebrate complexes, L. alburnoides males are fertile and play an important role in the dynamics of the complex. Moreover, diploid hybrid males may have initiated a tetraploidization process, when a diploid clonal sperm fertilised a diploid egg. This direct route to tetraploidy by originating fish with the right constitution for normal meiosis (symmetric), may eventually lead to a new sexually reproducing polyploid species. This case-study reinforces the significance of hybridisation and polyploidy in evolution and diversification of vertebrates.

Animals↗

Human gene mutation in pathology and evolution.

Mutations in human gene pathology and evolution represent two sides of the same coin in that the same mechanisms that have frequently been implicated in disease-associated mutagenesis appear also to have been involved in potentiating evolutionary change. Indeed, the mutational spectra of germline mutations responsible for inherited disease, somatic mutations underlying tumorigenesis, polymorphisms (either neutral or functionally significant) and differences between orthologous gene sequences exhibit remarkable similarities, implying that they may have causal mechanisms in common. Since these different categories of mutation share multiple unifying characteristics, they should no longer be viewed as distinct entities but rather as portions of a continuum of genetic change that links population genetics and molecular medicine with molecular evolution.

Biological Evolution↗

Development and use of microsatellite DNA loci for genetic ecotoxicological studies of the fathead minnow (Pimephales promelas).

The development of new DNA technologies has increased the opportunities to study the effect of genetic variation as a factor in selection, resistance, and fitness of individuals and populations. Genetic composition affects the evolutionary potential of an organism; however, whether genetic variation has a role in adaptation and survival due to chemical stress is still under debate. The strategy of measuring such variation should be based on the desired number of loci needed and degree of polymorphism at each locus. Microsatellite DNA loci (also known as Simple Tandem Repeats, STRs) have among the highest levels of variation within most eukaryotic genomes. Methods to determine the high levels of variation in individuals and populations have become more refined, making DNA-based studies in ecotoxicology more feasible. Herein, we describe the general characteristics of microsatellite DNA loci, their isolation, and their applications to toxicological studies using the fathead minnow (Pimephales promelas) as a focal species.

Adaptation, Physiological↗

Genetic analysis of benzoquinone production in Tribolium confusum.

Many species of tenebrionid beetles produce and secrete benzoquinones from specialized prothoracic and postabdominal glands. Tribolium confusum produces two compounds methyl-1,4-benzoquinone (MBQ) and ethyl-1,4-benzoquinone (EBQ). These compounds are hypothesized to function as external defense compounds, killing microbes and deterring predators, and their ability to evolve by natural selection depends on both selection and the genetic vs. environmental contribution to phenotypic variation. We crossed a strain of T. confusum that produces high quantities of benzoquinones, b-Pakistan, with a low-producing strain, b-+, and measured both the internal and external quantities of MBQ and EBQ for the two extreme strains and their F1 progeny. Internal amounts show a clear pattern of inheritance, with at least 50% of the phenotypic variation attributed to genotype. Additive and dominance coefficients for internal amounts indicate that the trait is additive with no significant dominance. In contrast, external quantities show little pattern of inheritance. The role of genetics and environment in determining quantities of secretory defensive compounds is important to elucidating the ecology and evolutionary potential of chemical defenses.

Adaptation, Physiological↗

Iron deficiency anaemia in young women.

OBJECTIVES: The expression density of GPIaIIa, the primary platelet collagen receptor (integrin alpha2beta1), is linked to two polymorphisms (GPIa-807C/T and HPA-5a/b). During evolution a gene shift from the genotypes GPIa-807CC-HPA-5bb to the genotypes GPIa-807CT-HPA-5aa has taken place. The aim of the study was to assess whether iron deficiency anaemia (e.g. increased blood loss) in young women could be associated with a specific genotype, indicating a role as potential evolutionary selection factor. STUDY DESIGN: Women between 18 and 40 yr of age presenting for their first blood donation were asked about alimentary habits and use of oral contraception. Haemoglobin and serum ferritin were measured and the GPIa-C807T and HPA-5 genotypes were determined. RESULTS: Two hundred women were included and grouped according to the WHO definition for iron deficiency anaemia (haemoglobin <121 g L(-1) and ferritin <15 microg L(-1)). Eight women fulfilled both WHO-criteria for iron deficiency anaemia, 145 women fulfilled none. No differences regarding age, use of oral contraceptives, alimentary habits, and HPA-5 were found between the groups. The GPIa-807CC genotype was strongly over-represented in the WHO-anaemic women as compared to the non-WHO-anaemic women (87.5% vs. 33.1%, P=0.003). CONCLUSION: Iron deficiency anaemia in young women might have been the evolutionary disadvantage causing the gene shift from GPIa-807CC to 807CT.

Adolescent↗

2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans.

As part of our effort to sequence the 100-megabase (Mb) genome of the nematode Caenorhabditis elegans, we have completed the nucleotide sequence of a contiguous 2,181,032 base pairs in the central gene cluster of chromosome III. Analysis of the finished sequence has indicated an average density of about one gene per five kilobases; comparison with the public sequence databases reveals similarities to previously known genes for about one gene in three. In addition, the genomic sequence contains several intriguing features, including putative gene duplications and a variety of other repeats with potential evolutionary implications.

Animals↗

Molecular breeding of viruses.

Genetic recombination is a major force driving the evolution of many viruses. Recombination between two copackaged retroviral genomes may occur at rates as high as 40% per replication cycle. This enables genetic information to be shuffled rapidly, leading to recombinants with new patterns of mutations and phenotypes. The in vitro process of DNA shuffling (molecular breeding) mimics this mechanism on a vastly parallel and accelerated scale. Multiple homologous parental sequences are recombined in parallel, leading to a diverse library of complex recombinants from which desired improvements can be selected. Different proteins and enzymes have been improved using DNA shuffling. We report here the first application of molecular breeding to viruses. A single round of shuffling envelope sequences from six murine leukaemia viruses (MLV) followed by selection yielded a chimaeric clone with a completely new tropism for Chinese Hamster Ovary (CHOK1) cells. The composition and properties of the selected clone indicated that this particular permutation of parental sequences cannot be readily attained by natural retroviral recombination. This example demonstrates that molecular breeding can enhance the inherently high evolutionary potential of retroviruses to obtain desired phenotypes. It can be an effective tool, when information is limited, to optimize viruses for gene therapy and vaccine applications when multiple complex functions must be simultaneously balanced.

3T3 Cells↗

Rapid evolution drives ecological dynamics in a predator-prey system.

Ecological and evolutionary dynamics can occur on similar timescales. However, theoretical predictions of how rapid evolution can affect ecological dynamics are inconclusive and often depend on untested model assumptions. Here we report that rapid prey evolution in response to oscillating predator density affects predator-prey (rotifer-algal) cycles in laboratory microcosms. Our experiments tested explicit predictions from a model for our system that allows prey evolution. We verified the predicted existence of an evolutionary tradeoff between algal competitive ability and defence against consumption, and examined its effects on cycle dynamics by manipulating the evolutionary potential of the prey population. Single-clone algal cultures (lacking genetic variability) produced short cycle periods and typical quarter-period phase lags between prey and predator densities, whereas multi-clonal (genetically variable) algal cultures produced long cycles with prey and predator densities nearly out of phase, exactly as predicted. These results confirm that prey evolution can substantially alter predator-prey dynamics, and therefore that attempts to understand population oscillations in nature cannot neglect potential effects from ongoing rapid evolution.

Animals↗

Uncovering cryptic genetic variation.

Cryptic genetic variation is the dark matter of biology: it is variation that is not normally seen, but that might be an essential source of physiological and evolutionary potential. It is uncovered by environmental or genetic perturbations, and is thought to modify the penetrance of common diseases, the response of livestock and crops to artificial selection and the capacity of populations to respond to the emergence of a potentially advantageous macro-mutation. We argue in this review that cryptic genetic variation is pervasive but under-appreciated, we highlight recent progress in determining the nature and identity of genes that underlie cryptic genetic effects and we outline future research directions.

Animals↗

The advantages and disadvantages of being polyploid.

Polyploids - organisms that have multiple sets of chromosomes - are common in certain plant and animal taxa, and can be surprisingly stable. The evidence that has emerged from genome analyses also indicates that many other eukaryotic genomes have a polyploid ancestry, suggesting that both humans and most other eukaryotes have either benefited from or endured polyploidy. Studies of polyploids soon after their formation have revealed genetic and epigenetic interactions between redundant genes. These interactions can be related to the phenotypes and evolutionary fates of polyploids. Here, I consider the advantages and challenges of polyploidy, and its evolutionary potential.

Evolution, Molecular↗

Genetic structure of fragmented populations of a threatened endemic percid of the Rhône river: Zingel asper.

Zingel asper is an endemic percid of the Rhône basin considered to be critically endangered. This species was continuously distributed throughout the Rhône in 1900, but today only occupies 17% of its initial area. In the present study, five microsatellite loci were used to assess the level of genetic variability within and among populations localized in different sub-basins. Contrasting results were obtained for the three main populations from the Rhône. A reduced allelic diversity was observed for the two populations displaying the lowest patch sizes (length of the river system occupied); of these, a recent genetic bottleneck was detected for the population showing a particularly low density. However, the third population was characterized by a relatively large spatial extent, high local fish concentrations and an allelic diversity that was twice as high and associated with an equilibrium between mutation and drift. Thus, this population shows an apparently better evolutionary potential for long-term survival. Since 1930, a marked fragmentation of the whole Rhône system has appeared, related to the development of dams, and we assume that the significant genetic differentiation detected between the populations could mainly reflect the impact of this fragmentation. The high turnover of the Z. asper populations, and the major role of dispersal in population persistence (highlighted in a recent population dynamics study), indeed suggest that the differentiation observed could mainly have arisen from habitat fragmentation in recent history.

Alleles↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗