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The origin of anti-GM1 antibodies in neuropathies: the "binding site drift" hypothesis.

Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. The origin of these autoantibodies is still unknown, although there is evidence that they are produced by CD5+ B-lymphocytes and that antigen mimicry is involved. Anti-GM, IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Gal beta1-3GalNAc and probably do not have GM1-mediated biological activity. Other anti-GM1 IgM-antibodies with higher affinity and/or different fine specificity are present in patients with motor syndromes. Based on our studies of structural requirement for binding, we hypothesize that disease-associated anti-GM1 antibodies originate at random by mutations affecting the binding site of naturally-occurring ones. The hypothesis is conceptually similar to the established phenomenon of "genetic drift" in species evolutionary biology and is therefore termed "binding site drift".

Autoantibodies↗

Specificity of the antibody response of rabbits to a self-antigen.

The demonstration that the antigenic determinants on rabbit cytochrome c that elicit antibodies in rabbits occur in regions of variability among mammalian cytochromes c suggests the existence of an evolutionary process which eliminates genetic specificities for self-determinants.

Amino Acid Sequence↗

Long-term stability of allozyme frequencies in a wood lemming, Myopus schisticolor, population with a biased sex ratio and density fluctuations.

Wood lemming (Myopus schisticolor) populations are characterized by female biased sex ratios and cyclic variations in population size. Both of these characteristics are assumed to reduce genetic variation and thus affect the evolutionary adaptation of the species. We addressed these questions by studying the genetic structure of a wood lemming population from eastern Finland by isozyme markers during a 21-year period, which corresponds to 40-50 generations. Contingency tests showed that genotypic proportions conformed to Hardy-Weinberg equilibrium in each of the four sampling years. Among the temporal replicates, allele frequencies differed most by 0.14 and were not significant. Genetic variation was also stable and fairly high with a mean observed heterozygosity of H = 0.057. Variability in the Heinavesi population was higher than previously reported in wood lemming. The difference was mainly caused by variation at a phosphoglucomutase locus that was monomorphic in earlier studies. Significant linkage disequilibrium was observed in three of the comparisons but the disequilibrium did not appear consistently in all years. This pattern was also evidenced by the variance components, which indicated that selection favoured for specific allele pairs only in few subsamples.

Animals↗

A single locus determines thelytokous parthenogenesis of laying honeybee workers (Apis mellifera capensis).

The evolution and maintenance of parthenogenetic species are a puzzling issue in evolutionary biology. Although the genetic mechanisms that act to restore diploidy are well studied, the underlying genes that cause the switch from sexual reproduction to parthenogenesis have not been analysed. There are several species that are polymorphic for sexual and parthenogenetic reproduction, which may have a genetic basis. We use the South African honeybee subspecies Apis mellifera capensis to analyse the genetic control of thelytoky (asexual production of female workers). Due to the caste system of honeybees, it is possible to establish classical backcrosses using sexually reproducing queens and drones of both arrhenotokous and thelytokous subspecies, and to score the frequency of parthenogenesis in the resulting workers. We found Mendelian segregation for thelytoky of egg-laying workers, which appears to be controlled by a single major gene (th). The segregation pattern indicates a recessive allele causing thelytoky. We found no evidence for maternal transmission of bacterial endosymbionts controlling parthenogenesis. Thelytokous parthenogenesis of honeybee workers appears to be a classical qualitative trait, because we did not observe mixed parthenogenesis (amphitoky), which might be expected in the case of multi-locus inheritance.

Animals↗

The origin and evolution of stereotyped patterns of macrochaetes on the nota of cyclorraphous Diptera.

A long-standing problem in evolutionary biology is how genetic variation arises within populations and evolves to make species anatomically different. Many of the morphological differences in body plans between animal groups are thought to result from changes in gene expression during development. The rules governing the structure and evolution of cis-regulatory gene sequences are unknown, however, and the evolution of traits between closely related species remains relatively unexplored at a molecular level. To study the evolution of gene regulation, it is necessary to find a tractable trait that varies between species and for which the genetic regulation is well known in at least one of the species. The stereotyped, two-dimensional pattern of bristles on the thorax of Drosophila has been intensively investigated and is due to a precise spatial expression of proneural genes. Other species of flies have different bristle patterns and so comparisons between them provide a good paradigm for the study of changes in gene regulation. Here, we review the current state of understanding of these changes.

Animals↗

Gene duplication, gene loss and evolution of expression domains in the vertebrate nuclear receptor NR5A (Ftz-F1) family.

Fushi tarazu factor 1 (Ftz-F1, NR5A) is a zinc-finger transcription factor that belongs to the nuclear receptor superfamily and regulates genes that are involved in sterol and steroid metabolism in gonads, adrenals, liver and other tissues. To understand the evolutionary origins and developmental genetic relationships of the Ftz-F1 genes, we have cloned four homologous Ftz-f1 genes in zebrafish, called ff1a, ff1b, ff1c and ff1d. These four genes have different temporal and spatial expression patterns during development, indicating that they have distinct mechanisms of genetic regulation. Among them, the ff1a expression pattern is similar to mammalian Nr5a2, while the ff1b pattern is similar to that of mammalian Nr5a1. Genetic mapping experiments show that these four ff1 genes are located on chromosome segments conserved between the zebrafish and human genomes, indicating a common ancestral origin. Phylogenetic and conserved synteny analysis show that ff1a is the orthologue of NR5A2, and that ff1b and ff1d genes are co-orthologues of NR5A1 that arose by a gene-duplication event, probably a whole-genome duplication, in the ray-fin lineage, and each gene is located next to an NR6A1 co-orthologue as in humans, showing that the tandem duplication occurred before the divergence of human and zebrafish lineages. ff1c does not have a mammalian counterpart. Thus we have characterized the phylogenetic relationships, expression patterns and chromosomal locations of these Ftz-F1 genes, and have demonstrated their identities as NR5A genes in relation to the orthologous genes in other species.

Animals↗

The evolutionary ecology of resistance to parasitoids by Drosophila.

Parasitoids are the most important natural enemies of many insect species. Larvae of many Drosophila species can defend themselves against attack by parasitoids through a cellular immune response called encapsulation. The paper reviews recent studies of the evolutionary biology and ecological genetics of resistance in Drosophila, concentrating on D. melanogaster. The physiological basis of encapsulation, and the genes known to interfere with resistance are briefly summarized. Evidence for within- and between-population genetic variation in resistance from isofemale line, artificial selection and classical genetic studies are reviewed. There is now firm evidence that resistance is costly to Drosophila, and the nature of this cost is discussed, and the possibility that it may involve a reduction in metabolic rate considered. Comparative data on encapsulation and metabolic rates across seven Drosophila species provides support for this hypothesis. Finally, the possible population and community ecological consequences of evolution in the levels of host resistance are examined.

Animals↗

Genetic analysis of ion channel dysfunction in Drosophila.

To dissect the molecular mechanisms of electrical activity in the nervous system, an extensive collection of mutations affecting various types of voltage-gated ion channels was identified and characterized in Drosophila. Most of these mutations were generated by chemical mutagenesis and were recognized on the basis of defects in motor behavior. These were the first genetically determined ion channelopathies to be characterized in any multicellular organism. Drosophila is a particularly attractive model system for such studies because of the availability of powerful genetic, electrophysiological, and molecular techniques for generating new mutations, characterizing their phenotypes, and cloning the genes thus defined. Consequently, a number of ion channels, including various types of K+ channels that had not yielded previously to biochemical approaches, were first identified via a genetic strategy in Drosophila. Evolutionary conservation of these genes enabled subsequent isolation of the corresponding genes from various mammals, including humans. Several of these human homologues have been found to be associated with heritable neuromuscular disorders. Studies of ion channel mutations in Drosophila have thus provided important biological information concerning the molecular and functional diversity of ion channels, their evolutionary relationships, and their in vivo functions in the nervous system. Similar studies of additional new mutations should now facilitate the analysis of ion channel regulatory mechanisms.

Animals↗

Gene silencing in a polyploid homosporous fern: paleopolyploidy revisited.

Because of their high chromosome numbers, homosporous vascular plants were considered paleopolyploids until recent enzyme electrophoretic studies rejected this hypothesis by showing that they express only diploid numbers of isozymes. In polyploid sporophytes of the homosporous fern pelleae rufa, however, progressive diminution of phosphoglucoisomerase activities encoded by one ancestral genome culminates in tetraploid plants exhibiting a completely diploidized electrophoretic phenotype for this enzyme. The demonstration that such gene silencing can make a polyploid fern look isozymically like a diploid questions the validity of isozyme evidence for testing the paleopolyploid hypothesis and supports the proposed role of polyploidization followed by genetic diploidizaton in the evolutionary history of homosporous pteridohytes.

Journal Article↗

Evidence for multiple adaptive peaks from populations of bacteria evolving in a structured habitat.

Natural selection tends to promote the divergence of populations living in different environments. Even in identical environments, however, replicate populations may diverge if they find alternative adaptive solutions. We describe the evolution of 18 bacterial populations (Comamonas sp.) founded from a single progenitor genotype and propagated separately for 1000 generations in two distinct environments, one physically unstructured (mass-action liquid) and the other structured (agar surfaces). Phenotypic diversity, as reflected in colony morphology, was greater in the structured habitat than in the unstructured habitat. More importantly, the trajectories for mean fitness, as measured by competition against the common ancestor, were more divergent for populations in the structured habitat than those in the unstructured habitat. Structured environments may accelerate evolutionary diversification by promoting genetic polymorphisms within populations, thereby increasing the complexity of genetic constraints that allow divergence among replicate populations.

Adaptation, Biological↗

Maintenance of pre-mRNA secondary structure by epistatic selection.

Linkage disequilibrium between polymorphisms in a natural population may result from various evolutionary forces, including random genetic drift due to sampling of gametes during reproduction, restricted migration between subpopulations in a subdivided population, or epistatic selection. In this report, we present evidence that the majority of significant linkage disequilibria observed in introns of the alcohol dehydrogenase locus (Adh) of Drosophila pseudoobscura are due to epistatic selection maintaining secondary structure of precursor mRNA (pre-mRNA). Based on phylogenetic-comparative analysis and a likelihood approach, we propose secondary structure models of Adh pre-mRNA for the regions of the adult intron and intron 2 where clustering of linkage disequilibria has been observed. Furthermore, we applied the likelihood ratio test to the phylogenetically predicted secondary structure in intron 1. In contrast to the other two structures, polymorphisms associated with the more conserved stem-loop structure of intron 1 are in low frequency, and linkage disequilibria have not been observed. These findings are qualitatively consistent with a model of compensatory fitness interactions. This model assumes that mutations disrupting pairing in a secondary structural element are individually deleterious if they destabilize a functionally important structure; a second "compensatory" mutation, however, may restabilize the structure and restore fitness.

Animals↗

A signal peptide that directs non-Sec transport in bacteria also directs efficient and exclusive transport on the thylakoid Delta pH pathway.

Signal peptides that specifically direct precursor proteins to the thylakoid Delta pH pathway possess an N domain RR motif. Signal peptides that direct transport of bacterial proteins across a non-Sec export pathway possess an N domain RRXFLK consensus motif. Recent genetic studies suggest an evolutionary link between these two protein translocation pathways. To further explore this relationship, we examined the thylakoid targeting capability of the signal peptide for Escherichia coli hydrogenase 1 small subunit (HyaA) by linking it to plastocyanin and assaying the chimeric protein in an in vitro thylakoid transport assay. The chimeric precursor was transported across thylakoids with high efficiency. Transport was characteristic of the Delta pH but not the Sec pathway, i.e. it was eliminated by ionophores that dissipate the DeltapH but occurred in the absence of stromal extract or ATP. This result was confirmed by competition with chemical quantities of a Delta pH pathway precursor. This indicates that the HyaA signal peptide has the necessary elements for efficient and exclusive targeting to the Delta pH pathway and further supports the notion that the alternate targeting pathways in prokaryotes and plant thylakoids are analogous.

Adenosine Triphosphatases↗

The genetic stability of a conditional live HIV-1 variant can be improved by mutations in the Tet-On regulatory system that restrain evolution.

Live attenuated human immunodeficiency virus type 1 (HIV-1) vaccines are considered unsafe because more quickly replicating pathogenic virus variants may evolve after vaccination. As an alternative vaccine approach, we have previously presented a doxycycline (dox)-dependent HIV-1 variant that was constructed by incorporating the tetracycline-inducible gene expression system (Tet-On system) into the viral genome. Replication of this HIV-rtTA variant is driven by the dox-inducible transcriptional activator rtTA and can be switched on and off at will. A large scale evolution study was performed to test the genetic stability of this conditional live vaccine candidate. In several long term cultures, we selected for HIV-rtTA variants that no longer required dox for replication. These evolved variants acquired a typical amino acid substitution either at position 19 or 37 in the rtTA protein. Both mutations caused rtTA activity and viral replication in the absence of dox. We designed a novel rtTA variant with a higher genetic barrier toward these undesired evolutionary routes. The corresponding HIV-rtTA variant did not lose dox control in long term cultures, demonstrating its improved genetic stability.

AIDS Vaccines↗

Parental effects on offspring longevity--evidence from 17th to 19th century reproductive histories.

BACKGROUND: Family studies provide support for a modest genetic influence on offspring life span, although the magnitude of these correlations is small. AIM: The study aimed to clarify the relative contributions of parental age at birth and overall parental longevity on offspring lifespan, and to identify the biological and cultural mechanisms. SUBJECTS AND METHODS: Information was derived from two village genealogies (1650-1927) encompassing 9979 births (5315 males, 4664 females). Data selection was guided by the inclusion of information about parental age at birth and lifespan, offspring lifespan and cohort-specific life expectancy. RESULTS: Parental age at reproduction displayed a negative association with offspring survivability, which was caused by a host of biological as well as environmental factors. In contrast, parental lifespan was positively associated with offspring age at death. These effects differed by parent's and child's sex. CONCLUSION: The maternal age effect on female progeny is thought to be indicative of a preferential genetic load. From an evolutionary point of view, direct selection for maternal lifespan may be an adaptive strategy to enhance child survival prospects.

Cohort Studies↗

The evolution of sexually selected traits and antagonistic androgen expression in actinopterygiian fishes.

Many sexually selected traits in male fishes are controlled by testosterone. Directional selection for male ornaments could theoretically increase male testosterone levels over evolutionary timescales, and when genetically correlated, female testosterone levels as well. Because of the negative fitness consequences of high testosterone, it is plausible that female choice for sexually selected traits in males results in decreased female reproductive fitness. I used comparative analysis to examine the association between male peak testosterone expression and sexually selected ornaments. I also tested for genetic correlation between male and female androgen levels. The presence of sexually selected traits in males was significantly correlated with increased peak androgen levels in males as well as females, and female testosterone levels were significantly correlated with male peak testosterone titers, although the slope was only marginally <1. This suggests that selection to decouple high male and female testosterone levels is either weak or otherwise ineffective.

Animals↗

Leaf evolution: gases, genes and geochemistry.

AIMS: This Botanical Briefing reviews how the integration of palaeontology, geochemistry and developmental biology is providing a new mechanistic framework for interpreting the 40- to 50-million-year gap between the origination of vascular land plants and the advent of large (megaphyll) leaves, a long-standing puzzle in evolutionary biology. SCOPE: Molecular genetics indicates that the developmental mechanisms required for leaf production in vascular plants were recruited long before the advent of large megaphylls. According to theory, this morphogenetic potential was only realized as the concentration of atmospheric CO2 declined during the late Palaeozoic. Surprisingly, plants effectively policed their own evolution since the decrease in CO2 was brought about as terrestrial floras evolved accelerating the rate of silicate rock weathering and enhancing sedimentary organic carbon burial, both of which are long-term sinks for CO2. CONCLUSIONS: The recognition that plant evolution responds to and influences CO(2) over millions of years reveals the existence of an intricate web of vegetation feedbacks regulating the long-term carbon cycle. Several of these feedbacks destabilized CO2 and climate during the late Palaeozoic but appear to have quickened the pace of terrestrial plant and animal evolution at that time.

Atmosphere↗

SPEED: a molecular-evolution-based database of mammalian orthologous groups.

MOTIVATION: The abundance of nucleotide sequence information available has expanded horizons of inquiry for molecular evolution; however, the full potential of whole-genome analysis has not been realized because of inadequate tools. Here, we present one of the first toolkits to aid multidisciplinary high-throughput analysis. SUMMARY: SPEED was created to integrate molecular evolutionary data with existing genetic resources and provide a straightforward user interface to 17,352 orthologous gene groups, containing representatives from eight mammalian species and an avian outgroup. AVAILABILITY: See http://bioinfobase.umkc.edu/speed/ for access.

Algorithms↗

Evolution of steroid-inducible RP2 mRNA expression in the mouse kidney.

We have examined the structure and expression of mRNAs encoded by the androgen-inducible RP2 gene in the kidneys of nine mouse species within the genus Mus. There is considerable interspecies variation in the lengths of the major RP2 transcripts; some of this variation is due to the presence or absence of a B1 repetitive element in the 3'-untranslated region of the gene. In addition, the extent of RP2 mRNA induction by testosterone differs among the species. Two species show 10-20-fold induction, while others display a reduced response or none at all. Analysis of an interspecific hybrid indicates that the inducibility phenotype is inherited in an additive fashion. A correlation between RP2 inducibility and the time of formation of lineages within the Mus genus suggests that induction evolved in a stepwise fashion, with the acquisition of a modest hormonal response being followed by the appearance of a greater response. The interspecies variations in RP2 mRNA structure and regulation provide a useful model for the identification and study of genetic elements that elicit evolutionary alterations in steroid-modulated gene expression.

Animals↗