Contrasted patterns of molecular evolution in dominant and recessive self-incompatibility haplotypes in Arabidopsis

Self-incompatibility has been considered by geneticists a model system for reproductive biology and balancing selection, but our understanding of the genetic basis and evolution of this molecular lock-and-key system has remained limited by the extreme level of sequence divergence among haplotypes, resulting in a lack of appropriate genomic sequences. In this study, we report and analyze the full sequence of eleven distinct haplotypes of the self-incompatibility locus (S-locus) in two closely related Arabidopsis species, obtained from individual BAC libraries. We use this extensive dataset to highlight sharply contrasted patterns of molecular evolution of each of the two genes controlling self-incompatibility themselves, as well as of the genomic region surrounding them. We find strong collinearity of the flanking regions among haplotypes on each side of the S-locus together with high levels of sequence similarity. In contrast, the S-locus region itself shows spectacularly deep gene genealogies, high variability in size and gene organization, as well as complete absence of sequence similarity in intergenic sequences and striking accumulation of transposable elements. Of particular interest, we demonstrate that dominant and recessive S-haplotypes experience sharply contrasted patterns of molecular evolution. Indeed, dominant haplotypes exhibit larger size and a much higher density of transposable elements, being matched only by that in the centromere. Overall, these properties highlight that the S-locus presents many striking similarities with other regions involved in the determination of mating-types, such as sex chromosomes in animals or in plants, or the mating-type locus in fungi and green algae.     

Rates of molecular evolution of primates

This review considers the history and the current state of the debatable issue of variation in accumulation rates of mutational substitutions in the phylogeny of humans and other primates. Arguments pro and contra the hypothesis on gradually decreasing tempo of molecular evolution of humans and apes are discussed. It is shown that data on proteins and (nuclear and mitochondrial) DNA confirm this hypothesis. The conclusion is drawn that the total rate of mutation accumulation is determined by a number of interacting factors. The primary of these factors in most cases (including that of hominids) is generation time, which is closely associated with the number of germ cell divisions. At the same time, fixation rates of nonsynonymous substitutions are also affected by various forms of selection.     

Rates and patterns of chromosome evolution in enteric bacteria

Although several types of large-scale alterations potentially affect the structure and organization of bacterial genomes, recent analyses of physical maps and complete genomic sequences reveal that chromosome heterogeneity in enteric bacteria has resulted from the acquisition and deletion of large segments of DNA. These acquired sequences can provide novel functions immediately upon their introduction and play a significant role in the diversification of bacterial species.     

Effects of gene expression on molecular evolution in Arabidopsis thaliana and Arabidopsis lyrata

We analyzed the complete genome sequence of Arabidopsis thaliana and sequence data from 83 genes in the outcrossing A. lyrata, to better understand the role of gene expression on the strength of natural selection on synonymous and replacement sites in Arabidopsis. From data on tRNA gene abundance, we find a good concordance between codon preferences and the relative abundance of isoaccepting tRNAs in the complete A. thaliana genome, consistent with models of translational selection. Both EST-based and new quantitative measures of gene expression (MPSS) suggest that codon preferences derived from information on tRNA abundance are more strongly associated with gene expression than those obtained from multivariate analysis, which provides further support for the hypothesis that codon bias in Arabidopsis is under selection mediated by tRNA abundance. Consistent with previous results, analysis of protein evolution reveals a significant correlation between gene expression level and amino acid substitution rate. Analysis by MPSS estimates of gene expression suggests that this effect is primarily the result of a correlation between the number of tissues in which a gene is expressed and the rate of amino acid substitution, which indicates that the degree of tissue specialization may be an important determinant of the rate of protein evolution in Arabidopsis.     

Rates of molecular evolution: the hominoid slowdown

It is proposed that early in phylogeny a large proportion of amino acid substitutions were selectively neutral, but that bursts of adaptive substitutions during major radiations of life so increased selective constraints that most mutations in modern proteins are detrimental. Recent findings on DNA nucleotide sequences indicate that decreasing mutation rates further slowed the rate of molecular evolution in the lineage to humans.     

Evolution of haplodiploidy: Models for inbred and outbred systems

Several new models are proposed for the evolution of haplodiploidy. Each of these models is evaluated for its ability to explain (1) special problems associated with transition to haplodiploidy from a population of diplodiploid progenitors, (2) current patterns of population structure in haplodiploid and related species, and (3) the evolution of genetic systems similar but not identical to haplodiploid systems. Of the new models, three are based on special conditions associated with inbreeding. Close inbreeding provides for the automatic effects of reduced problems in expressing recessives, lowered differences in gain from heterozygosity (to produce both heterotic effects and a greater variety of offspring) between haploid and diploid males, effective protection of haploids from direct competition with diploids, and a mechanism for the spread of haplodiploidy through gains derived from increased ability to control sex ratio. These models differ in the context where gain from sex ratio control is expressed. Pathways for the evolution of haplodiploidy in outbreeding populations are also discussed. Females who parthenogenetically produce haploid males have high genetic relatedness to their sons. If the sperm of these males is used to make both sons and daughters, i.e., through matings with diplodiploid females, there may be a net gain for haplodiploids. Another outbreeding model, modified from S. W. Brown (1964, Genetics49, 797–817), deals with selection for females producing haploid males in populations where there are driving sex chromosomes. Biases created by drive in sex ratio may allow haplodiploid females to be the only effective producers of males in the population. Several of the new models explain the whole range of haplodiploid and related adaptations and provide predictions that appear to be more consistent with the known structure of contemporary populations than those available in current models.     

Different patterns in molecular evolution of the Triticeae

A huge part of the genomes of most Triticeae species is formed by different families of repetitive DNA sequences. In this paper the phylogenetic distribution of two major classes of the repeats, retrotransposons and tandemly organized DNA sequences, are considered and compared with the evolution of gene-rich regions and generally accepted Triticeae phylogenetic relationships. In Hordeum, LTR-containing retrotransposons are dispersed along the chromosomes and are consistent with the existing picture of the phylogeny of Hordeum. Another retrotransposon class, LINEs, have evolved independently from LTR-retrotransposons. Different retrotransposon classes appear to have competed for genome space during the evolution of Hordeum. Another class of repeats, tandemly organized DNA sequences, tends to cluster at the functionally important regions of chromosomes, centromeres and telomeres. The distribution of a number of tandem DNA families in Triticeae is not congruent with generally accepted phylogenetic relationships. While natural selection is the dominant factor determining the structure of genic regions we suggest that the contribution of random events is important in the evolution of repetitive DNA sequences. The interplay of stochastic processes, molecular drive, and selection determines the structure of chromosomal regions, notably at centromeres and telomeres, stabilizing and differentiating species-specific karyotypes. Thus, the evolution of these regions may occur largely independently of the evolution of gene-rich regions.     

Rates and patterns of chromosomal evolution in Drosophila pseudoobscura and D. miranda

Comparisons of gene orders between species permit estimation of the rate of chromosomal evolution since their divergence from a common ancestor. We have compared gene orders on three chromosomes of Drosophila pseudoobscura with its close relative, D. miranda, and the distant outgroup species, D. melanogaster, by using the public genome sequences of D. pseudoobscura and D. melanogaster and approximately 50 in situ hybridizations of gene probes in D. miranda. We find no evidence for extensive transfer of genes among chromosomes in D. miranda. The rates of chromosomal rearrangements between D. miranda and D. pseudoobscura are far higher than those found before in Drosophila and approach those for nematodes, the fastest rates among higher eukaryotes. In addition, we find that the D. pseudoobscura chromosome with the highest level of inversion polymorphism (Muller's element C) does not show an unusually fast rate of evolution with respect to chromosome structure, suggesting that this classic case of inversion polymorphism reflects selection rather than mutational processes. On the basis of our results, we propose possible ancestral arrangements for the D. pseudoobscura C chromosome, which are different from those in the current literature. We also describe a new method for correcting for rearrangements that are not detected with a limited set of markers.     

Preference for own versus conspecific pups by inbred and outbred rats

Communal care of young may occur when related females live in close proximity to each other. The degree of relatedness between females may affect discrimination of own from conspecific young. Retrieval tests were used to examine preference for own versus conspecific pups by inbred and outbred rats. Dams were given retrieval tests in a neutral arena every other day from day 1 through 10 postpartum. Outbred, but not inbred, dams showed a significant preference for their own pups. Outbred dams also retrieved pups more slowly than did inbred dams. Differences in the behavior of dams and/ or similarity of cues presented by pups may be responsible for the lack of preference for own pups shown by inbred dams. The results of this study suggest that indiscriminate care of young should occur when closely related females share a nest.     

Enzyme polymorphism in feral, outbred and inbred rats (Rattus norvegicus).

Polymorphism at 25 loci coding for liver enzymes was studied in two feral, three outbred and three inbred rat strains by starch gel electrophoresis. No variation was found at 14 loci, and a low degree of polymorphism was detected at three. Eight loci were polymorphic in more than one population. The average degree of heterozygosity per locus per individual feral rat was 0-07. The degrees of heterozygosity observed in the outbred and inbred strains were lower, from 0-006 to 0-012. Contrary to expectation, the inbred strains were neither monomorphic nor appreciably less heterozygous than the outbred ones. The heterozygosity of the inbred strains was primarily due to two polymorphic loci, G-3-pdh and alpha-Gpdh. The reason for this polymorphism is probably the superior homeostasis of the heterozygotes.     

Influence of antigen stimulation on the oxidative stress parameters in outbred and inbred rabbits

The influence of antigen stimulation on the oxidative stress parameters in two groups of rabbits-inbred and outbred were explored by evaluation of the level of lipid peroxidation products (MDA) in the plasma membrane, and the activity of erythrocyte antioxidant defense enzymes superoxide dismutase (SOD) and catalase (CAT). There was not a significant difference between levels of MDA in inbred and outbred rabbits before immunization. However, SOD activity in inbred rabbits was significantly increased in comparison with that of outbred (p = 0.006). Significantly higher plasma levels of lipid peroxidation products were detected in both inbred and outbred rabbits during immune response in comparison to the corresponding groups before immunization (p = 0.008 and p = 0.002). SOD and CAT activities in erythrocytes of rabbits during immune response were also significantly increased compared to that before immunization. In addition, during immune response SOD and CAT activities were found to be positively correlated to each other in both inbred and outbred rabbits (r = 0.727 and r = 0.916). In conclusion, our results suggest the presence of an increased oxidative stress during the antigen stimulation accompanied by an adaptive increase of SOD and CAT activities. 30 days after immunization, the plasma levels of MDA and the activities of SOD and CAT in erythrocytes decreased and reached values close to the controls.     

Rates of molecular evolution and the fraction of nucleotide positions free to vary

Summary Selective constraints on DNA sequence change were incorporated into a model of DNA divergence by restricting substitutions to a subset of nucleotide positions. A simple model showed that both mutation rate and the fraction of nucleotide positions free to vary are strong determinants of DNA divergence over time.When divergence between two species approaches the fraction of positions free to vary, standard methods that correct for multiple mutations yield severe underestimates of the number of substitutions per site. A modified method appropriate for use with DNA sequence, restriction site, or thermal renaturation data is derived taking this fraction into account. The model also showed that the ratio of divergence in two gene classes (e.g., nuclear and mitochondrial) may vary widely over time even if the ratio of mutation rates remains constant.DNA sequence divergence data are used increasingly to detect differences in rates of molecular evolution. Often, variation in divergence rate is assumed to represent variation in mutation rate. The present model suggests that differing divergence rates among comparisons (either among gene classes or taxa) should be interpreted cautiously. Differences in the fraction of nucleotide positions free to vary can serve as an important alternative hypothesis to explain differences in DNA divergence rates.     

Characterization of pathology and parasite load in outbred and inbred mouse models of chronic Neospora caninum infection

Here, we analyzed histological findings and parasite burden in chronic Neospora caninum infection in BALB/c and ICR mice and studied the correlation between lesion severity and parasite load in brain. To obtain a better understanding of the infection, we examined the influence of various host pathogen factors. Groups of outbred (ICR) and inbred (BALB/c) mice were inoculated using several NC-1 parasite doses (4 x 10(5), 10(6), and 5 x 10(6) tachyzoites), inoculation routes (intraperitoneal and subcutaneous), and 3 immunosuppressive treatments (methylprednisolone, cyclophosphamide, and vinblastine). Lesion severity was analyzed in the liver, lung, heart, and brain tissues, and parasite load was measured by real-time polymerase chain reaction in brain tissue. The results indicated more severe cerebral lesions and higher brain parasite burdens in inbred than in outbred mice. Hepatic tissue was the primary lesion site in immunosuppressed ICR mice. We also observed that increased inoculum size was reflected in greater lesion severity and a higher cerebral parasite load. No difference was observed with respect to inoculation route. The study also showed an association between brain parasite burden and severity of cerebral lesions in BALB/c mice.     

Functional polymorphisms in inbred rat strains and their allele frequencies in commercially available outbred stocks.

Polymorphisms that have been proven to influence gene functions are called functional polymorphisms. It is significant to know the distribution of functional polymorphisms in the rat, widely used in animal models for human diseases. In this study, we assessed 16 functional polymorphisms consisting of 3 coat color and 13 disease-associated genes in 136 rat strains, as a part of the genetic profiling program of the National Bio Resource Project for the Rat (NBRP-Rat). Polymorphisms of Cdkn1a, Fcgr3, Grp10, Lss, and Fdft1, which were proven to function in prostate tumorigenesis, glomerulonephritis, hyperphagia, and cholesterol biosynthesis, were shared among various inbred strains. These findings indicated that most rat strains harbored the disease-associated alleles and suggested that many unidentified functional polymorphisms might exist in inbred rat strains. The functional polymorphisms shared in inbred strains were also observed within outbred stocks available commercially. Therefore, this implies that experimental plans based on either rat inbred strains or outbred stocks need to be carefully designed with a full understanding of the genetic characteristics of the animals. To select the most suitable strains for experiments, the NBRP-Rat will periodically improve and update the genetic profiles of rat strains.