Microsatellites reveal heterosis in red deer

The fitness consequences of inbreeding and outbreeding are poorly understood in natural populations. We explore two microsatellite-based variables, individual heterozygosity (likely to correlate with recent inbreeding) and a new individual-specific internal distance measure, mean d2 (focusing on events deeper in the pedigree), in relation to two measures of fitness expressed early in life, birth weight and neonatal survival, in 670 red deer calves (Cervus elaphus) born on the Isle of Rum between 1982 and 1996. For comparison, we also analyse inbreeding coefficients derived from pedigrees in which paternity was inferred by molecular methods. Only 14 out of 231 calves (6.1%) had non-zero inbreeding coefficients, and neither inbreeding coefficient nor individual heterozygosity was consistently related to birth weight or neonatal survival. However, mean d2 was consistently related to both fitness measures. Low mean d2 was associated with low birth weight, especially following cold Aprils, in which foetal growth is reduced. Low mean d2 was also associated with low neonatal survival, but this effect was probably mediated by birth weight because fitting birth weight to the neonatal survival model displaced mean d2 as an explanatory variable. We conclude that in the deer population fitness measures expressed early in life do not show evidence of inbreeding depression, but they do show evidence of heterosis, possibly as a result of population mixing. We also demonstrate the practical problems of estimating inbreeding via pedigrees compared with a direct marker-based estimate of individual heterozygosity. We suggest that, together, individual heterozygosity and mean d2, estimated using microsatellites, are useful tools for exploring inbreeding and outbreeding in natural population.     

Mutant alleles of small effect are primarily responsible for the loss of fitness with slow inbreeding in Drosophila melanogaster

Multilocus simulation is used to identify genetic models that can account for the observed rates of inbreeding and fitness decline in laboratory populations of Drosophila melanogaster. The experimental populations were maintained under crowded conditions for approximately 200 generations at a harmonic mean population size of Nh approximately 65-70. With a simulated population size of N = 50, and a mean selective disadvantage of homozygotes at individual loci approximately 1-2% or less, it is demonstrated that the mean effective population size over a 200-generation period may be considerably greater than N, with a ratio matching the experimental estimate of Ne/Nh approximately 1.4. The buildup of associative overdominance at electrophoretic marker loci is largely responsible for the stability of gene frequencies and the observed reduction in the rate of inbreeding, with apparent selection coefficients in favor of the heterozygote at neutral marker loci increasing rapidly over the first N generations of inbreeding to values approximately 5-10%. The observed decline in fitness under competitive conditions in populations of size approximately 50 in D. melanogaster therefore primarily results from mutant alleles with mean effects on fitness as homozygotes of sm < or = 0.02. Models with deleterious recessive mutants at the background loci require that the mean selection coefficient against heterozygotes is at most hsm approximately 0.002, with a minimum mutation rate for a single Drosophila autosome 100 cM in length estimated to be in the range 0.05-0.25, assuming an exponential distribution of s. A typical chromosome would be expected to carry at least 100-200 such mutant alleles contributing to the decline in competitive fitness with slow inbreeding.     

Clusters of new identical mutants and the fate of underdominant mutations

Given favorable environmental and demographic conditions, premeiotic clusters of identical mutations can produce a broad distribution of the initial frequency of underdominant alleles. Because of these clusters, new underdominant mutations may not necessarily be as rare in a population as previously assumed. The fixation of underdominant mutations, especially those with low heterozygous fitness, is increased when mutations appear in a cluster due to a genetic change that occurred before germline differentiation. Most restrictions on the fixation of underdominant mutations in a single population, such as strong genetic drift, weak selection against mutant heterozygotes, isolated population structure, inbreeding, meiotic drive, and selection in favor of mutant homozygotes can be relaxed or even dropped. Instead, the fate of strong underdominant mutations is determined mainly by ecological and genetic factors that affect the cluster size distribution of new premeiotic mutations. Accumulation of reproductive isolation by the fixation of underdominant mutations becomes more feasible with clusters, and mutation is not always the weakest force during this evolutionary process. The large mean and variance of reproductive success in many multicellular species make it possible that even underdominant mutations with very low heterozygous fitness could contribute substantially to reproductive isolation.     

Alternative techniques for the clinical assessment of foot pronation

It has been known for decades that MHC genes play a critical role in the cellular immune response, but only recent research has provided a better understanding of how these molecules might affect mate choice. Original studies in inbred mouse strains revealed that mate choice was influenced by MHC dissimilarity. Detection of MHC differences between individuals in these experiments was related to olfactory cues, primarily in urine. Recent studies in humans have shown an analogous picture of MHC-based mating. Taken together, these findings could support either the hypothesis of MHC-based inbreeding avoidance or the hypothesis of MHC-related avoidance of reproductive failure, since studies in mice, humans and pigtailed macaques have shown that parental sharing of certain MHC alleles correlates with frequent spontaneous abortion or prolonged intergestational intervals. Data from many mammalian species clearly demonstrate that reproductive failure occurs as a result of inbreeding. Therefore, MHC similarity might serve as an indicator of genome-wide relatedness. In contrast, increased fitness due to the presence of individual MHC alleles in a pathogenic environment could explain MHC-based selection of currently good genes. Specifically, the physical condition of long-living animals depends on the ability to respond to immunological challenge and an individual's MHC alleles determine the response, since, unlike the T cell receptors, MHC alleles are not somatically recombined. Therefore, sexual selection of condition-dependent traits during mate choice could be used to select successful MHC alleles, thereby providing offspring with a higher relative immunity in their pathogenic environment.     

Evolution, emotions, and emotional disorders.

Emotions research is now routinely grounded in evolution, but explicit evolutionary analyses of emotions remain rare. This article considers the implications of natural selection for several classic questions about emotions and emotional disorders. Emotions are special modes of operation shaped by natural selection. They adjust multiple response parameters in ways that have increased fitness in adaptively challenging situations that recurred over the course of evolution. They are valenced because selection shapes special processes for situations that have influenced fitness in the past. In situations that decrease fitness, negative emotions are useful and positive emotions are harmful. Selection has partially differentiated subtypes of emotions from generic precursor states to deal with specialized situations. This has resulted in untidy emotions that blur into each other on dozens of dimensions, rendering the quest for simple categorically distinct emotions futile. Selection has shaped flexible mechanisms that control the expression of emotions on the basis of an individual's appraisal of the meaning of events for his or her ability to reach personal goals. The prevalence of emotional disorders can be attributed to several evolutionary factors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic architecture of olfactory discriminative avoidance conditioning in Drosophila melanogaster..

Recent claims to have demonstrated associative learning ability in fruitflies raise questions about the adaptive significance of behavioral modifiability of this species. In a strain survey and a 9?×?9 half diallel cross study of olfactory discriminative avoidance conditioning, a low narrow heritability and strong directional dominance or heterosis controlling nonrandom phenotypic variation were found. Furthermore, the predicted inbreeding depression and asymmetrical response to bidirectional genetic selection were both observed. The genetic architecture revealed in these 3 experiments is consistent with a close association between this conditioning phenotype and evolutionary fitness. Predictions from this interpretation to the nature of new mutations have been confirmed, and a possible role for conditioning in courtship behavior has been identified. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A variety of epistatic interactions can occur between partially homologous transgene loci brought together by sexual crossing

Epistatic interactions between unlinked transgene loci in tobacco plants were studied following sexual crosses between different transgenic lines. Three potential "modifier" transgene loci, which were structurally similar but integrated at different chromosomal locations, were tested for their ability to influence the expression of a partially homologous "target" transgene locus. After introduction of an individual modifier locus, the target locus could be either unaffected, completely inactivated and methylated or differentially sensitive, showing more complete inactivation and methylation when homozygous than when hemizygous. The implications of these results for inbreeding depression in plants are discussed.     

An ecology of text: using text retrieval to study alife on the net

I introduce a new alife model, an ecology based on a corpus of text, and apply it to the analysis of posts to USENET News. In this corporal ecology posts are organisms, the newsgroups of NetNews define an environment, and human posters situated in their wider context make up a scarce resource. I apply latent semantic indexing (LSI), a text retrieval method based on principal component analysis, to distill from the corpus those replicating units of text. LSI arrives at suitable replicators because it discovers word co-occurrences that segregate and recombine with appreciable frequency. I argue that natural selection is necessarily in operation because sufficient conditions for its occurrence are met: replication, mutagenicity, and trait/fitness covariance. I describe a set of experiments performed on a static corpus of over 10,000 posts. In these experiments I study average population fitness, a fundamental element of population ecology. My study of fitness arrives at the unhappy discovery that a flame-war, centered around an overly prolific poster, is the king of the jungle.     

Immunohistochemical demonstration of FSH and LH in the pituitary of the developing frog, Rana esculenta

The analytical, intra-individual and inter-individual variations as well as the best storage conditions were determined for erythrocyte glutathione, and the reference values were established. A total of 396 apparently healthy people, 206 male, and 190 female, were randomly selected from villages and cities of the southern part of Turkey. The distribution was Gaussian and no significant difference was observed between the male and the female subjects. The mean (standard deviation) of the population investigated for glutathione was 6.9 (1.0) mumol/gHb. The analytical, intra-individual and inter-individual variations were assessed in 20 apparently healthy subjects and were found to be 4.63%, 13.67% and 11.16%, respectively. Whole blood stored at -70 degrees C for up to 10 days was shown to be the best storage condition for erythrocyte glutathione determination. The results of the index of individuality showed that glutathione reference values could be used for diagnostic purposes.     

From replicators to reproducers: the first major transitions leading to life

A classification of replicators is proposed: life depends on replicators that can exist in an indefinitely large number of forms (unlimited heredity), and whose replication is modular rather than processive. The first template replicators would have increased at a rate less than exponential, because of self-inhibition arising from molecular complementarity. The result would be the survival of a varied population of replicators, rather than the victory of one type. This variability was important, because inaccurate copying meant that individual replicators were small (Eigen's paradox). The origin of cooperation between replicators, and the problem of molecular parasites, are discussed. Today, cooperation depends on cellular compartments, and on the linkage of genes on chromosomes, but we argue that at an earlier stage surface metabolism, in which replicators react only with neighbours, was important. The origin of translation and the genetic code is discussed. The essential step is the binding of amino acids to specific oligonucleotides. We suggest that this binding originated, not as a step in protein synthesis, but in the formation of coenzymes in a metabolically complex RNA world. Existing organisms are not replicators (that is, new individuals do not arise by copying), but reproducers that contain replicators. We outline Griesemer's concept of a reproducer, which brings out the essential role of development in evolution.     

Regulation of IRF and STAT gene expression by retinoic acid

Ex vivo production of cytokines as determined by whole blood stimulation and supernatant ELISA is partly determined by heritability. To assess the ability of this system to distinguish between high and low producers the laboratory error and individual variation were investigated. Whole blood samples from healthy volunteers were collected using endotoxin-free tubes and were incubated with 0 to 1000 ng/ml lipopolysaccharide concentrations for 4 and 24 h, and subsequently centrifuged. In the supernatants, TNF-alpha and IL10 were measured by ELISA. Coefficients of variation for the day-to-day variation in the blood sampling, transport and stimulation as well as in the whole blood stimulation per se ranged from 7.5% to 12.3%. The intra-individual variation was 15% (TNF-alpha) and 19% (IL10) in contrast to the inter-individual variation of, on average, 35%. No interchanging of ranks between high and low producers was observed after repeating the whole blood stimulation on distinct days. The whole blood stimulation system is able to distinguish high and low producers of TNF-alpha and IL10.     

Intermediate sequences increase the detection of homology between sequences

Two homologous sequences, which have diverged beyond the point where their homology can be recognised by a simple direct comparison, can be related through a third sequence that is suitably intermediate between the two. High scores, for a sequence match between the first and third sequences and between the second and the third sequences, imply that the first and second sequences are related even though their own match score is low. We have tested the usefulness of this idea using a database that contains the sequences of 971 protein domains whose structures are known and whose residue identities with each other are some 40% or less (PDB40D). On the basis of sequence and structural information, 2143 pairs of these sequences are known to have an evolutionary relationship. FASTA, in an all-against-all comparison of the sequences in the database, detected 320 (15%) of these relationships as well as three false positive (i.e. 1% error rate). Using intermediate sequences found by FASTA matches of PDB40D sequences to those in the large non-redundant OWL database we could detect 550 evolutionary relationships with an error rate of 1%. This means the intermediate sequence procedure increases the ability to recognise the evolutionary relationships amongst the PDB40D sequences by 70%.     

The preference for GT-rich DNA by the yeast Rad51 protein defines a set of universal pairing sequences

The Rad51 protein of Saccharomyces cerevisiae is a eukaryotic homolog of the RecA protein, the prototypic DNA strand-exchange protein of Escherichia coli. RAD51 gene function is required for efficient genetic recombination and for DNA double-strand break repair. Recently, we demonstrated that RecA protein has a preferential affinity for GT-rich DNA sequences-several of which exhibit enhanced RecA protein-promoted homologous pairing activity. The fundamental similarity between the RecA and Rad51 proteins suggests that Rad51 might display an analogous bias. Using in vitro selection, here we show that the yeast Rad51 protein shares the same preference for GT-rich sequences as its prokaryotic counterpart. This bias is also manifest as an increased ability of Rad51 protein to promote the invasion of supercoiled DNA by homologous GT-rich single-stranded DNA, an activity not previously described for the eukaryotic pairing protein. We propose that the preferred utilization of GT-rich sequences is a conserved feature among all homologs of RecA protein, and that GT-rich regions are loci for increased genetic exchange in both prokaryotes and eukaryotes.     

Evolution of MHC genetic diversity: a tale of incest, pestilence and sexual preference

Evidence from the house mouse (Mus) suggests that the extreme diversity of genes of the major histocompatibility complex (MHC) results from three different forms of selection involving infectious disease (pestilence), inbreeding (incest) and MHC-based mating (sexual) preferences. MHC-based disassortative mating preferences are presumed to have evolved because they reduce homozygosity throughout the genome, and particularly within loci linked to the MHC. Progeny derived from such disassortative matings would enjoy increased fitness because of both reduced levels of inbreeding depression and increased resistance to infectious disease arising from their increased MHC heterozygosity.     

OptiLam:Design of Optimised Rolling Schedules

Nowadays it is known that the thermomechanical schedules applied during hot rolling of flat products provide the steel with improved mechanical properties.In this work an optimisation tool,OptiLam (OptiLam v.1),based on a predictive software and capable of generating optimised rolling schedules to obtain the desired mechanical properties in the final product is described.OptiLam includes some well-known metallurgical models which predict microstructural evolution during hot rolling and the transformation austenite/ferrite during the cooling.Furthermore,an optimisation algorithm,which is based on the gradient method,has been added,in order to design thermomechanical sequences when a specific final grain size is desired.OptiLam has been used to optimise rolling parameters,such as strain and temperature.Here,some of the results of the software validation performed by means of hot torsion tests are presented,showing also the functionality of the tool.Finally,the application of classical optimisation models,based on the gradient method,to hot rolling operations,is also discussed.     

Changes in pain perception and pain-related somatosensory evoked potentials in humans produced by exposure to oscillating magnetic fields

cDNA selection was used to isolate coding sequences from cosmids mapping to the gene-rich telomeric region of human chromosome 21q. A novel cDNA, termed SMT3A, was isolated and mapped between the loci PFKL and D21S171, about 2.2 Mb proximal to the telomere. The predicted protein of 103 amino acids appears to be a homologue of the Saccharomyces cerevisiae SMT3 protein, whose gene was previously isolated as a suppressor of mutations in the MIF2 gene. The yeast MIF2 gene encodes an essential centromeric protein and shows homology to mammalian CENP-C, an integral component of active kinetochores. SMT3A was found to be highly homologous to two other recently isolated human genes, suggesting the presence of a new gene family. Homologous sequences were also found in protozoa, metazoa, and plants. Moreover, all predicted proteins show significant homology to ubiquitin. The proposed role of yeast SMT3 as centromeric protein and the strong evolutionary conservation of the SMT3A gene suggest an involvement of the encoded protein in the function and/or structure of the eukaryotic kinetochore.     

Output rates among coil winders.

Week-to-week variation in output for a group of 27 coil winders, over a 38-week period, was studied. The inter-week correlations for employees ranged from—.03 to .91; the median r was .64. The significance of this great intra-individual variation, which exceeded inter-individual variation, is discussed, and explanatory hypotheses are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evolutionary biology and personality psychology: Toward a conception of human nature and individual differences.

Identifies several key issues in personality psychology, focusing on the distinction between approaches emphasizing species-typical tendencies and those emphasizing systematic variation around those tendencies. Typological and population approaches in evolutionary biology are discussed, highlighting the alternative aims, assumptions, methods, and limitations of each. Genotypic universality, automaticity, and adaptation are examined as potential criteria for identifying important species-typical characteristics; and heritability, inclusive fitness, sexual selection, and assortative mating are evaluated as criteria for designating important individual differences. Suggestions are made for resolving some of the conceptual and operational difficulties entailed by implementing these criteria. It is argued that, although substantial problems remain, evolutionary biology can provide a means for identifying relations between individual differences and species-typical characteristics. (92 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of mating system differences on nucleotide diversity at the phosphoglucose isomerase locus in the plant genus Leavenworthia

To test the theoretical prediction that highly inbreeding populations should have low neutral genetic diversity relative to closely related outcrossing populations, we sequenced portions of the cytosolic phosphoglucose isomerase (PgiC) gene in the plant genus Leavenworthia, which includes both self-incompatible and inbreeding taxa. On the basis of sequences of intron 12 of this gene, the expected low diversity was seen in both populations of the selfers Leavenworthia uniflora and L. torulosa and in three highly inbreeding populations of L. crassa, while high diversity was found in self-incompatible L. stylosa, and moderate diversity in L. crassa populations with partial or complete self-incompatibility. In L. stylosa, the nucleotide diversity was strongly structured into three haplotypic classes, differing by several insertion/deletion sequences, with linkage disequilibrium between sequences of the three types in intron 12, but not in the adjacent regions. Differences between the three kinds of haplotypes are larger than between sequences of this gene region from different species. The haplotype divergence suggests the presence of a balanced polymorphism at this locus, possibly predating the split between L. stylosa and its two inbreeding sister taxa, L. uniflora and L. torulosa. It is therefore difficult to distinguish between different potential causes of the much lower sequence diversity at this locus in inbreeding than outcrossing populations. Selective sweeps during the evolution of these populations are possible, or background selection, or merely loss of a balanced polymorphism maintained by overdominance in the populations that evolved high selfing rates.     

Peptide design aided by neural networks: biological activity of artificial signal peptidase I cleavage sites

De novo designed signal peptidase I cleavage sites were tested for their biological activity in vivo in an Escherichia coli expression and secretion system. The artificial cleavage site sequences were generated by two different computer-based design techniques, a simple statistical method, and a neural network approach. In previous experiments, a neural network was used for feature extraction from a set of known signal peptidase I cleavage sites and served as the fitness function in an evolutionary design cycle leading to idealized cleavage site sequences. The cleavage sites proposed by the two algorithms were active in vivo as predicted. There seems to be an interdependence between several cleavage site features for the constitution of sequences recognized by signal peptidase. It is concluded that neural networks are useful tools for sequence-oriented peptide design.