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Additive genetic variation under intraspecific competition and stabilizing selection: a two-locus study.

A diallelic two-locus model is investigated in which the loci determine the genotypic value of a quantitative trait additively. Fitness has two components: stabilizing selection on the trait and a frequency-dependent component, as induced, for instance, if the ability to utilize different food resources depends on this trait. Since intraspecific competition induces disruptive selection, this model leads to a conflict of selective forces. We study how the underlying genetics (recombination rate and allelic effects) interacts with the selective forces, and explore the resulting equilibrium structure. For the special case of equal effects, global stability results are proved. Unless the locus effects are sufficiently different, the genetic variance maintained at equilibrium displays a threshold-like dependence on the strength of competition. For loci with equal effects, the equilibrium fitnesses of genotypic values exhibit disruptive selection if and only if competition is strong enough to maintain a stable two-locus polymorphism. For unequal effects, disruptive selection can be observed for weaker competition and in the absence of a stable polymorphism.

Animals↗

Does viviparity evolve in cold climate reptiles because pregnant females maintain stable (not high) body temperatures?

Viviparity (live bearing) has evolved from egg laying (oviparity) in many lineages of lizards and snakes, apparently in response to occupancy of cold climates. Explanations for this pattern have focused on the idea that behaviorally thermoregulating (sun-basking) pregnant female reptiles can maintain higher incubation temperatures for their embryos than would be available in nests under the soil surface. This is certainly true at very high elevations, where only viviparous species occur. However, comparisons of nest and lizard temperatures at sites close to the upper elevational limit for oviparous reptiles (presumably, the selective environment where the transition from oviparity to viviparity actually occurs) suggest that reproductive mode has less effect on mean incubation temperatures than on the diel distribution of those temperatures. Nests of the oviparous scincid lizard Bassiana duperreyi showed smooth diel cycles of heating and cooling. In contrast, body temperatures of the viviparous scincid Eulamprus heatwolei rose abruptly in the morning, were high and stable during daylight hours, and fell abruptly at night. Laboratory incubation experiments mimicking these patterns showed that developmental rates of eggs and phenotypic traits of hatchling B. duperreyi were sensitive to this type of thermal variance as well as to mean temperature. Hence, diel distributions as well as mean incubation temperatures may have played an important role in the selective forces for viviparity. More generally, variances as well as mean values of abiotic factors may constitute significant selective forces on life-history evolution.

Animals↗

Origins of the machinery of recombination and sex.

Mutation plays the primary role in evolution that Weismann mistakenly attributed to sex. Homologous recombination, as in sex, is important for population genetics--shuffling of minor variants, but relatively insignificant for large-scale evolution. Major evolutionary innovations depend much more on illegitimate recombination, which makes novel genes by gene duplication and by gene chimaerisation--essentially mutational forces. The machinery of recombination and sex evolved in two distinct bouts of quantum evolution separated by nearly 3 Gy of stasis; I discuss their nature and causes. The dominant selective force in the evolution of recombination and sex has been selection for replicational fidelity and viability; without the recombination machinery, accurate reproduction, stasis, resistance to radical deleterious evolutionary change and preservation of evolutionary innovations would be impossible. Recombination proteins betray in their phylogeny and domain structure a key role for gene duplication and chimaerisation in their own origin. They arose about 3.8 Gy ago to enable faithful replication and segregation of the first circular DNA genomes in precellular ancestors of Gram-negative eubacteria. Then they were recruited and modified by selfish genetic parasites (viruses; transposons) to help them spread from host to host. Bacteria differ fundamentally from eukaryotes in that gene transfer between cells, whether incidental to their absorptive feeding on DNA and virus infection or directly by plasmids, involves only genomic fragments. This was radically changed by the neomuran revolution about 850 million years ago when a posibacterium evolved into the thermophilic cenancestor of eukaryotes and archaebacteria (jointly called neomurans), radically modifying or substituting its DNA-handling enzymes (those responsible for transcription as well as for replication, repair and recombination) as a coadaptive consequence of the origin of core histones to stabilise its chromosome. Substitution of glycoprotein for peptidoglycan walls in the neomuran ancestor and the evolution of an endoskeleton and endomembrane system in eukaryotes alone required the origin of nuclei, mitosis and novel cell cycle controls and enabled them to evolve cell fusion and thereby the combination of whole genomes from different cells. Meiosis evolved because of resulting selection for periodic ploidy reduction, with incidental consequences for intrapopulation genetic exchange. Little modification was needed to recombination enzymes or to the ancient bacterial catalysts of homology search by spontaneous base pairing to mediate chromosome pairing. The key innovation was the origin of meiotic cohesins delaying centromere splitting to allow two successive divisions before reversion to vegetative growth and replication, necessarily yielding two-step meiosis. Also significant was the evolution of synaptonemal complexes to stabilise bivalents and of monopolins to orient sister centromeres to one spindle pole. The primary significance of sex was not to promote evolutionary change but to limit it by facilitating ploidy cycles to balance the conflicting selective forces acting on rapidly growing phagotrophic protozoa and starved dormant cysts subject to radiation and other damage.

Animals↗

Analysis of an observational rating scale for repetition, posture, and force in selected manufacturing settings.

OBJECTIVE: The aim of this work was to quantify the interrater reliability of a set of scales that assess repetition, posture, and force as used on site when examining industrial work. BACKGROUND: Interrater reliability of observational assessment methods can vary depending on the definition of the methods and situations in which they are used. METHOD: In several industries, 846 jobs were assessed using pairs of analysts to rate the repetition, force, and posture of the upper limbs. Twelve analysts with varying experience levels participated. RESULTS: Using an interclass correlation coefficient (ICC), force and repetition had reliability values of .60 and .71 before and .82 and .87 after discussion, respectively. After discussion, peak posture ratings had ICCs of .60 to .83. ICCs for average posture ratings ranged from .31 to .51 initially to .55 to .67 in final ratings. Less experienced analysts changed their initial ratings more than did the senior investigators. CONCLUSION: The high interrater reliability of the repetition and force metrics indicates that a single analyst is appropriate for basic job assessment. Posture ratings benefit greatly from a two-analyst system. Average postures should be assessed across a full range of the scale for interrater reliability assessment. Analyst pairs should be rotated to avoid forming biases. APPLICATION: For basic assessments of forceful exertions and repetitive motions, a single analyst can be used, reducing the resource requirements for both industry and large epidemiological studies.

Humans↗

Developmental constraints and wing shape variation in natural populations of Drosophila melanogaster.

The body sizes and shapes of poikilothermic animals generally show clinal variation with latitude. Among the environmental factors responsible for the cline, temperature seems to be the most probable candidate. In the present work we analysed natural populations of Drosophila melanogaster collected at different geographical localities to determine whether the same selective forces acting on wing development in the laboratory are also at work in the wild. We show that the temperature selection acting on wing development in the laboratory is only one of the selective forces operating in the wild. The size differences between natural populations seem to depend exclusively on cell number whereas they depend on cell area in the laboratory. The two wing compartments behave as distinct units of selection subjected to different genetic control, confirming our previous observations on laboratory populations. In addition, subunits of development defined as regions of cell proliferation centres restricted within longitudinal veins can, in turn, be considered as subunits of selection. Their interaction during development and continuous natural selection around an optimum could explain the high wing shape stability generally found in natural populations.

Animals↗

The evolution of sexes.

It is very likely that sexual differentiation into two morphologically indistinguishable mating types has preceded the evolution of anisogamy. Therefore, the study of the evolution of mating types in an isogamous population is more informative for understanding the forces responsible for the evolution of different sexes than the study of the evolution of anisogamy; the latter represents the secondary problem of how, after the establishment of two sexes, an increasing degree of gamete dimorphism may evolve. Mating type evolution has been analyzed theoretically in population genetic models. These explorations show that mating types may evolve as a consequence of selection for more efficient gamete recognition, and also as a result of intragenomic conflict between nuclear and cytoplasmic DNA. However, in both cases the selection forces have to be very strong, which makes these possible explanations less convincing. Nearly all theories proposed for the evolution of anisogamy assume two conflicting selection forces to be relevant: selection for greater gamete productivity, and selection for greater zygote size. Although the explanation is intuitively plausible, the comparative evidence is a bit disappointing. Alternatively, anisogamy can be explained as a side-effect of selection for a greater efficiency in finding a mating partner by using sexual pheromones. Firm empirical evidence is lacking, however. In both problem areas--mating type evolution and anisogamy evolution--experimental work is badly needed.

Animals↗

Generation of diversity in retroviruses.

Retroviruses are unique in that their propagation includes transfer of genetic information from RNA to DNA. Two enzymes (RT and RNA polymerase II) that participate in their replication process do not encode editing functions and are thus "error prone." Current estimates indicate that up to one nucleotide substitution per genome occurs per retrovirus replication cycle. In addition, rearrangements can occur during reverse transcription. These mutations result in viral populations in which the wild-type sequence can only be defined by consensus. Retroviruses are also unusual among viruses in their high recombination frequency, which is the result of the copackaging, and then reverse transcribing of two different RNA genomes in the same particle. Recombinants are formed during copying of RNA templates into DNA. With the ability to mutate and recombine genetic information at a higher rate, retroviral populations are poised to respond to selective forces, which may increase or decrease replication of particular genotypes. Interspecies transmission of retroviruses or retroviral genes also likely plays a role in generating diversity. Endogenous proviruses exist in the germline of many vertebrates; pedigrees indicate that recent infections of the germline have also occurred. Thus, the selective forces that mold the retroviral genome may be opposing: selection for efficient replication as exogenous viruses versus selection for passive replication as endogenous proviruses. The latter may be more advantageous over the course of evolution since the survival of the retrovirus is ensured by survival of the host organism. Segments of endogenous viruses may reappear in exogenous viruses through recombination and thus these endogenous sequences are perpetuated.

Animals↗

Genetic polymorphism of the swine major histocompatibility complex ( SLA) class I genes, SLA-1, -2 and -3.

In order to identify and characterize genetic polymorphism of the swine major histocompatibility complex ( Mhc: SLA) class I genes, RT-PCR products of the second and third exons of the three SLA classical class I genes, SLA-1, SLA-2 and SLA-3 were subjected to nucleotide determination. These analyses allowed the identification of four, eight and seven alleles at the SLA-1, SLA-2 and SLA-3 loci, respectively, from three different breeds of miniature swine and one mixed breed. Among them, 12 alleles were novel. Construction of a phylogenetic tree using the nucleotide sequences of those 19 alleles indicated that the SLA-1 and -2 genes are more closely related to each other than to SLA-3. Selective forces operating at single amino acid sites of the SLA class I molecules were analyzed by the Adaptsite Package program. Ten positive selection sites were found at the putative antigen recognition sites (ARSs). Among the 14 positively selected sites observed in the human MHC ( HLA) classical class I molecules, eight corresponding positions in the SLA class I molecules were inferred as positively selected. On the other hand, four amino acids at the putative ARSs were identified as negatively selected in the SLA class I molecules. These results suggest that selective forces operating in the SLA class I molecules are almost similar to those of the HLA class I molecules, although several functional sites for antigen and cytotoxic T-lymphocyte recognition by the SLA class I molecules may be different from those of the HLA class I molecules.

Alleles↗

Natural selection and the evolution of genome imprinting.

Sexual reproduction results from the fusion of gametes in which the chromatin configuration of maternal and paternal chromosomes is distinct at fertilization. Although many of the differences are erased during successive cellular divisions and chromatin modifications, some are retained in both somatic and germline cells. These epigenetic modifications can confer different characteristics on maternal and paternal chromosomes and such differences can be selected during any process that has the ability to distinguish between homologues. The end result of these selective forces are parental origin effects, writ large. The range of effects observed, including transcriptional imprinting and effects on chromosome segregation and heterochromatization, reflects the diversity of selective forces in operation. However, a closer look at these effects suggests that parental origin-dependent differences in chromatin structure might be subject to some common forces and that these forces may explain many of the "nontranscriptional" parental origin effects observed in mammals.

Animals↗

Effects of environmental changes on natural selection active on human polygenic traits.

During the last century, industrialized countries experienced such an improvement in socioeconomic conditions and in sanitation that it is likely that the selective forces active on human metric traits have been modified. Perinatal mortality as a function of birth weight is one of the clearest examples of natural selection in humans. Here, trends over time of stabilizing and directional selection associated with birth weight have been analyzed in Japan from 1969 to 1989. The population of newborns has been subdivided according to gestational age, which is one of the main covariates of birth weight. The results show that in full-term babies both stabilizing and directional selection are coming to an end, whereas in babies born after 8 months of gestation these selective forces are still active, even if at much lower levels than in the past. The peculiar results found in the 7-month-gestation population are probably due to grossly abnormal cases of immaturity.

Birth Weight↗

Polymorphism of a complex resistance gene candidate family in wild populations of common bean (Phaseolus vulgaris) in Argentina: comparison with phenotypic resistance polymorphism.

Fifteen populations of wild bean (Phaseolus vulgaris), located in three provinces in Argentina, were analysed for their polymorphism for a complex resistance gene candidate (RGC) family clustered on the genome and for resistance phenotypes to strains of Colletotrichum lindemuthianum. Results indicate that RGC polymorphism is high. Population structure obtained for markers related to resistance was compared to population structure obtained for RAPD markers in order to infer the evolutionary forces driving polymorphism for resistance in wild populations at both molecular and phenotypic levels. Hierarchical analysis of differentiation showed that, within provinces, populations were differentiated for RAPD as well as for molecular and phenotypic markers of resistance. In contrast, provinces were differentiated only for RAPD and RGC markers and not for resistance phenotypes. The discrepancies found between diversity structures for molecular markers (RAPD and RGCs) and for resistance phenotypes suggest an effect of selection and indicate that diversity for resistance may not be driven by the same selective forces at the molecular and phenotypic levels. We further discuss whether specific selective forces are exerted on RGC markers and underline the importance of spatial scale of analysis for demonstrating an impact of selection.

Argentina↗

The action of selection on codon bias in the human genome is related to frequency, complexity, and chronology of amino acids.

BACKGROUND: The question of whether synonymous codon choice is affected by cellular tRNA abundance has been positively answered in many organisms. In some recent works, concerning the human genome, this relation has been studied, but no conclusive answers have been found. In the human genome, the variation in base composition and the absence of cellular tRNA count data makes the study of the question more complicated. In this work we study the relation between codon choice and tRNA abundance in the human genome by correcting relative codon usage for background base composition and using a measure based on tRNA-gene copy numbers as a rough estimate of tRNA abundance. RESULTS: We term major codons to be those codons with a relatively large tRNA-gene copy number for their corresponding amino acid. We use two measures of expression: breadth of expression (the number of tissues in which a gene was expressed) and maximum expression level among tissues (the highest value of expression of a gene among tissues). We show that for half the amino acids in the study (8 of 16) the relative major codon usage rises with breadth of expression. We show that these amino acids are significantly more frequent, are smaller and simpler, and are more ancient than the rest of the amino acids. Similar, although weaker, results were obtained for maximum expression level. CONCLUSION: There is evidence that codon bias in the human genome is related to selection, although the selection forces acting on codon bias may not be straightforward and may be different for different amino acids. We suggest that, in the first group of amino acids, selection acts to enhance translation efficiency in highly expressed genes by preferring major codons, and acts to reduce translation rate in lowly expressed genes by preferring non-major ones. In the second group of amino acids other selection forces, such as reducing misincorporation rate of expensive amino acids, in terms of their size/complexity, may be in action. The fact that codon usage is more strongly related to breadth of expression than to maximum expression level supports the notion, presented in a recent study, that codon choice may be related to the tRNA abundance in the tissue in which a gene is expressed.

Amino Acids↗

Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment.

Emergence of invasive behavior in cancer is life-threatening, yet ill-defined due to its multifactorial nature. We present a multiscale mathematical model of cancer invasion, which considers cellular and microenvironmental factors simultaneously and interactively. Unexpectedly, the model simulations predict that harsh tumor microenvironment conditions (e.g., hypoxia, heterogenous extracellular matrix) exert a dramatic selective force on the tumor, which grows as an invasive mass with fingering margins, dominated by a few clones with aggressive traits. In contrast, mild microenvironment conditions (e.g., normoxia, homogeneous matrix) allow clones with similar aggressive traits to coexist with less aggressive phenotypes in a heterogeneous tumor mass with smooth, noninvasive margins. Thus, the genetic make-up of a cancer cell may realize its invasive potential through a clonal evolution process driven by definable microenvironmental selective forces. Our mathematical model provides a theoretical/experimental framework to quantitatively characterize this selective pressure for invasion and test ways to eliminate it.

Adaptation, Physiological↗

Restrictive flamenco alleles are maintained in Drosophila melanogaster population cages, despite the absence of their endogenous gypsy retroviral targets.

The flamenco (flam) locus, located at 20A1-3 in the centromeric heterochromatin of the Drosophila melanogaster X chromosome, is a major regulator of the gypsy/mdg4 endogenous retrovirus. In restrictive strains, functional flam alleles maintain gypsy proviruses in a repressed state. By contrast, in permissive strains, proviral amplification results from infection of the female germ line and subsequent insertions into the chromosomes of the progeny. A restrictive/permissive polymorphism prevails in natural and laboratory populations. This polymorphism was assumed to be maintained by the interplay of opposite selective forces; on one hand, the increase of genetic load caused by proviral insertions would favor restrictive flam alleles because they make flies resistant to these gypsy replicative transpositions and, on the other, a hypothetical resistance cost would select against such alleles in the absence of the retrovirus. However, the population cage data presented in this paper do not fit with this simple resistance cost hypothesis because restrictive alleles were not eliminated in the absence of functional gypsy proviruses; on the contrary, using 2 independent flam allelic pairs, the restrictive frequency rose to about 90% in every experimental population, whatever the pair of alleles and the allelic proportions in the initial inoculum. These data suggest that the flam polymorphism is maintained by some strong balancing selection, which would act either on flam itself, independently of the deleterious effect of gypsy, or on a hypothetical flanking gene, in linkage disequilibrium with flam. Alternatively, restrictive flam alleles might also be resistant to some other retroelements that would be still present in the cage populations, causing a positive selection for these alleles. Whatever selective forces that maintain high levels of restrictive alleles independently of gypsy, this unknown mechanism can set up an interesting kind of antiviral innate immunity, at the population level.

Alleles↗

Evaluation of stresses and forces in selected I-bars using the finite element method.

PURPOSE: Three-dimensional models of half-round, tapered and full-round, untapered I-bar clasps of varying configurations and material properties were constructed. The purpose of this study was to examine the stresses and reaction forces produced within each model upon deflection to 0.01 in (0.254 mm), 0.02 in (0.508 mm), and 0.03 in (0.762 mm) at 1 mm from the tip using the finite element method. MATERIALS AND METHODS: Three-dimensional computer models of half-round and full-round clasps were constructed using solid eight-node brick elements. The half-round, tapered I-bar clasp model was 2.4 and 1.4 mm in diameter at the base and tip, respectively. The full-round, untapered I-bar clasp model was 1 mm in diameter. Three design groups were created for each clasp form. Group A had 25% of the total length in the straight anchor end of the I-bar clasp, B had 35%, and C had 50%. All models were 31 mm in length and had a radius of curvature of 5 mm. Different material properties were incorporated into the models. Each model was deflected at a point 1 mm from the tip to 0.01 in (0.254 mm), 0.02 in (0.508 mm), and 0.03 in (0.762 mm). RESULTS: The stresses and forces produced as a result of the deflection applied to each clasp were viewed and displayed graphically. The maximum von Mises stresses in megapascals and the reaction force in newtons (N) were recorded. Stresses varied in each clasp in the range of 0 to 154.3 MPa for the half-round, tapered I-bar clasp models, and 0 to 100.9 MPa for the full-round I-bar clasp models at 0.01-in deflection. Reaction force measured near the tip of the clasp models was between 1.60 N and 6.31 N for the half-round, and between 0.22 N to 2.13 N for the full-round I-bar clasp models. For all clasps studied, as the deflection increased, the location of stress within each group remained the same regardless of the material properties; however, the stress and force values increased linearly. CONCLUSIONS: The location of maximum stress varied with the length of the anchor portion of the clasps studied. Maximum stresses were located on the flat side of the half-round, tapered I-bar clasp model.

Color↗

The mutant distribution of an RNA species replicated by Q beta replicase.

The mutant spectrum of an RNA species that is replicated by Q beta replicase, MNV-11, was investigated by retrotranscribing the RNA to DNA and cloning it into plasmids. The sequences of several cDNA clones of MNV-11 populations amplified by Q beta replicase under various conditions were determined and compared. A surprisingly broad mutant distribution was found: the consensus sequence never made up more than 40% of the total population and was accompanied by many mutants. Most mutants had several base exchanges, insertions and/or deletions; up to nine of the total 86 nucleotides were changed. The mutants found had replication rates comparable to that of the wild-type and were thus enriched in the population by selection forces. When the growth conditions were changed, the mutant distribution centre was shifted. The published consensus sequence of MNV-11 did not have the highest growth rate of the mutants, but was rather the best adapted to the various selection forces governing the growth phases the replicating RNA went through, i.e. it had found an optimal compromise between the rates of overall replication, enzyme binding and double strand formation.

Base Sequence↗

Molecular epidemiology of coagulase-negative staphylococci causing sepsis in a neonatal intensive care unit over an 11-year period.

Coagulase-negative staphylococci (CoNS) are the major causative microorganisms in neonatal nosocomial sepsis. Previous studies have shown that CoNS sepsis in the neonatal intensive care unit (NICU) is caused by predominant molecular types that are widely distributed among both neonates and staff. Some of these molecular types may persist in the NICU for years. The purpose of the present study was to determine the dynamic behavior of CoNS strains causing sepsis over a prolonged period of time by determining the molecular types of all blood isolates from septicemic infants over a period of 11 years (1991 to 2001). The results show that neonatal CoNS sepsis is increasingly caused by a few predominant molecular clusters. The most striking finding was that in recent years one molecular cluster emerged as the predominant cause of neonatal CoNS sepsis, responsible for no less than 31% (20 of 65) of blood isolates in 2001. Antibiotic resistance, particularly beta-lactam resistance, is probably an important selective force considering the high mecA gene carriage of CoNS blood isolates (70 to 92%). We conclude that neonatal CoNS sepsis is increasingly caused by a limited number of predominant molecular CoNS types and that antibiotic resistance is probably a major selective force.

Coagulase↗

Selection on the human immunodeficiency virus type 1 proteome following primary infection.

Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly homogeneous viral population first emerges and then diversifies over time due to selective forces that are poorly understood. To identify these forces, we conducted an intensive longitudinal study of viral genetic changes and T-cell immunity in one subject at < or =17 time points during his first 3 years of infection, and in his infecting partner near the time of transmission. Autologous peptides covering amino acid sites inferred to be under positive selection were powerful for identifying HIV-1-specific cytotoxic-T-lymphocyte (CTL) epitopes. Positive selection and mutations resulting in escape from CTLs occurred across the viral proteome. We detected 25 CTL epitopes, including 14 previously unreported. Seven new epitopes mapped to the viral Env protein, emphasizing Env as a major target of CTLs. One-third of the selected sites were associated with epitopic mutational escapes from CTLs. Most of these resulted from replacement with amino acids found at low database frequency. Another one-third represented acquisition of amino acids found at high database frequency, suggesting potential reversions of CTL epitopic sites recognized by the immune system of the transmitting partner and mutation toward improved viral fitness in the absence of immune targeting within the recipient. A majority of the remaining selected sites occurred in the envelope protein and may have been subjected to humoral immune selection. Hence, a majority of the amino acids undergoing selection in this subject appeared to result from fitness-balanced CTL selection, confirming CTLs as a dominant selective force in HIV-1 infection.

Amino Acid Sequence↗