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PubMed1999

Molecular epidemiology and evolutionary genetics of Leischmania parasites.

In order to illustrate the relevance of the concepts and methods of evolutionary genetics in the understanding of the epidemiology of pathogenic agents, we develop in this paper the case of the Leishmania, a genus of parasitic protozoa. An extensive study of various natural populations of Leishmania in different countries (Old and New World) was carried out by using Multilocus Enzyme Electrophoresis (MLEE) and Random Amplified Polymorphic DNA fingerprinting (RAPD) as genetic markers. The data have been interpreted in evolutionary genetic terms. The main benefit of this approach has been to better define the concept of species in the genus Leishmnania, on rigorous phylogenetic bases. As a matter of fact, a sound taxonomical background is a prerequisite for any epidemiological approach. Since the biological concept of species is difficult or impossible to apply for most pathogenic microorganisms, we recommend relying on criteria of both phylogenetic discreteness and of epidemiological/medical relevance to describe new species of Leishmania. Through this approach, for example, we have shown that the species status of L. ( V.) perzzl.ianza can be supported. On the contrary, we have been unable to clearly distinguish L. (V.) panamensis from L. (V.) guyanensis with genetic tools. Additionally, we have shown that the epidemiological inferences based on a limited set of genetic markers can be misleading. As a matter of fact, we have demonstrated that a collection of L. (L.) infantum stocks identified as zymodeme 'MON 1' by other authors present additional genetic heterogeneity and do not correspond to a distinct 'Discrete Typing Unit' DTU, and are actually polyphyletic. Lastly, in the samples that were conveniently designed, we have confirmed that Leishmania parasites have a basically clonal population structure. As the clonal model specifies it, occasional bouts of genetic exchange remain nevertheless possible. Telling comparisons are drawn with the evolutionary genetics of other pathogens Trypanosoma cruzi and Trypanosoma congolense.

Animals↗
PubMed2004

eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data.

The introduction of multilocus sequence typing (MLST) for the precise characterization of isolates of bacterial pathogens has had a marked impact on both routine epidemiological surveillance and microbial population biology. In both fields, a key prerequisite for exploiting this resource is the ability to discern the relatedness and patterns of evolutionary descent among isolates with similar genotypes. Traditional clustering techniques, such as dendrograms, provide a very poor representation of recent evolutionary events, as they attempt to reconstruct relationships in the absence of a realistic model of the way in which bacterial clones emerge and diversify to form clonal complexes. An increasingly popular approach, called BURST, has been used as an alternative, but present implementations are unable to cope with very large data sets and offer crude graphical outputs. Here we present a new implementation of this algorithm, eBURST, which divides an MLST data set of any size into groups of related isolates and clonal complexes, predicts the founding (ancestral) genotype of each clonal complex, and computes the bootstrap support for the assignment. The most parsimonious patterns of descent of all isolates in each clonal complex from the predicted founder(s) are then displayed. The advantages of eBURST for exploring patterns of evolutionary descent are demonstrated with a number of examples, including the simple Spain(23F)-1 clonal complex of Streptococcus pneumoniae, "population snapshots" of the entire S. pneumoniae and Staphylococcus aureus MLST databases, and the more complicated clonal complexes observed for Campylobacter jejuni and Neisseria meningitidis.

Algorithms↗
PubMed1989

Partial 6q deletion in a human salivary gland adenocarcinoma.

G-banding analysis was performed on a cultured human salivary gland adenocarcinoma. Clonal chromosome abnormalities consisted of a 6q- marker and loss of the Y chromosome. The 6q- marker had resulted from a long arm interstitial deletion, del(6)(q22q24). The present results, together with our previous findings of 6q deletions in other types of salivary gland tumors, indicate that deletions of 6q are characteristic for the karyotypic evolution of all major types of malignant salivary gland tumors. A common pathogenetic mechanism for these tumors might well be loss of a tumor suppressor gene located on 6q.

Adenocarcinoma↗
PubMed1996

Gains and losses of DNA sequences in malignant mesothelioma by comparative genomic hybridization.

The molecular basis of malignant mesothelioma is poorly known. We examined genetic changes in 11 mesothelioma specimens by comparative genomic hybridization (CGH). Five DNA specimens originated from uncultured tumor tissues and six from cell lines established from the same patients. Findings from the classical karyotypic characterization of both primary tumors and cell lines have been reported previously. In the CGH analyses the most common genetic alterations in the 11 mesothelioma specimens were losses of chromosomal regions in 1p, 8p, 14q, and 22q and gains of 5p, 6p, 8q, 15q, 17q, and 20. The cell lines had on average a much higher total number of genetic changes than the uncultured tumor specimens. Clonal relationship between the cell lines and the uncultured tissue specimens could not usually be demonstrated even though they originated from the same patient. The observed differences may partly be due to high frequency of chromosomal rearrangements, which CGH cannot detect, partly due to contamination of tumor specimens with normal tissue, and partly due to genetic evolution in tumor cell lines.

Chromosome Aberrations↗
PubMed2003

Peering through the looking glass at a sexual parasite: are Amazon mollies red queens?

The gynogenetic Amazon molly (Poecilia formosa) is a clonal, all-female lineage of livebearing fish that faces an unusual obstacle to evolutionary persistence. Sperm from heterospecific males (either sailfin, P. latipinna, or Atlantic, P. mexicana, mollies) is necessary to trigger embryogenesis. However, none of the male's genes are incorporated into the genome of the gynogenetic offspring. Some investigators have proposed that the evolution of male mate discrimination is a result of this cost, leading to a coevolutionary arms race between male avoidance of P. formosa and P. formosa attractiveness. Given that P. formosa successfully reproduces and has not yet gone extinct, it is clear there are mechanisms by which they attract the sexual attention of males. Although a Red Queen coevolutionary process in typical host/parasite systems has been shown to favor the persistence of sexual species, in this system an arms race has been invoked to explain the reverse. Here I present behavioral data supporting a more parsimonious scenario: that mechanisms of attraction in P. formosa are simply a consequence of its hybrid origin. Poecilia latipinna and P. mexicana males do not discriminate between gynogenetic P. formosa females and first generation sexual hybrid females, and females do not differ in agonistic behaviors associated with competition for mates. Both results contradict predictions from the Red Queen hypothesis. Therefore, coevolution is not necessary to explain the apparent evolutionary persistence of P. formosa.

Animals↗
PubMedDate not supplied

The common gammac-cytokines and transplantation tolerance.

Transplant rejection, like tolerance, is a T cell-dependent event. There is compelling evidence to suggest that induction of transplant tolerance is an actively learned process in which T cells need to engage the alloantigens in order to learn to tolerate the allograft. A family of cytokines whose receptors use the same IL-2 receptor gamma chain (also called the common gammac) plays an important role in regulating multiple aspects of the allograft response (i.e. rejection vs. tolerance). It is undeniable that gammac-cytokines can drive clonal expansion and effector maturation of alloreactive T cells, and therefore, targeting such cytokines or their receptor components remains an attractive way of blocking transplant rejection. However, we just started to appreciate that gammac-cytokines also regulate the acquisition of transplant tolerance via programming activated T cells for apoptotic cell death and via guiding the evolution of regulatory T cells. Thus, understanding precisely the role of gammac-cytokines in regulating T cell homeostasis and T cell regulation is critically important in the induction of transplant tolerance.

Animals↗
PubMed1990

Hematopoietic stem cell- and marrow stromal cell-specific requirements for gamma irradiation leukemogenesis in vitro.

The hematopoietic and stromal cell-specific properties of the cells involved in gamma irradiation leukemogenesis in vitro were defined. Cocultivation of clonal factor-dependent (FD), interleukin 3 (IL-3)-dependent cell lines 32D cl 3 or B6SUtA, or dual IL-3-/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell lines FDC-P1 or bg/bg d64 was carried out with clonal stromal cell lines D2XRII, GB1/6, +/+ 2.4, or Sld3. FD cell lines were added to control or 5000-cGy-irradiated plateau phase monolayer cultures of each stromal cell line, and parameters of stem cell engraftment and malignant transformation in vitro were quantitated. Cobblestone island formation by FD cells, cumulative production of nonadherent hematopoietic cells, and evolution of tumorigenic factor-independent (FI) subclonal lines were quantitated over 5-8 weeks. There was no detectable evolution of FI sublines with 32D cl 3, B6SUtA, or bg/bg d64 cells cocultivated with control or irradiated Sld3 stromal cells. IL-3-dependent cell lines 32D cl 3 or B6SUtA formed small 10- to 49-cell cobblestone "clusters" at low frequency on control or irradiated D2XRII, showed limited proliferation for less than 1 week, and showed no detectable evolution of FI cell lines. Subclones of 32D cl 3 derived by transfection and expression of recombinant oncogenes v-sis, or c-myc, or the epidermal growth factor receptor remained factor dependent and did not transform to factor independence after cocultivation with irradiated stromal cell lines. In contrast, cell line bg/bg d64, and each of seven subclonal lines of FDC-P1, including subclones selected for growth in GM-CSF, formed abundant cobblestone island colonies of greater than or equal to 50 cells on irradiated D2XRII stromal cells, produced non-adherent cells over 5-8 weeks, and showed evolution of tumorigenic FI subclonal lines. The data provide evidence for stable biological differences in both the hematopoietic and stromal cell components of the in vitro model of gamma irradiation leukemogenesis.

Animals↗
PubMed1996

Somatically mutated B cell pool provides precursors for insulin antibodies.

Antibodies to insulin are products of autoreactive B lymphocytes that escape inactivation or clonal deletion and are examples of "clonal ignorance." To understand the genetic origin of Abs from clonally ignorant B cells, the roles of somatic mutation and germ-line V(H) structures were examined for two murine IgG1 mAb that bind human and rodent insulin. Engineered mAb constructs that express germ-line or mutated V(H) genes show that somatic mutations introducing aspartic acid in or adjacent to CDRH2 play a key role in insulin binding. When either of the two anti-insulin V(H) regions is returned to its germ-line (unmutated) sequence, neither mAb binds insulin and the germ-line-encoded mAb are not polyreactive. Reconstruction of the somatic evolution of insulin binding in both mAbs shows that a single mutation in CDRH2 is sufficient to generate anti-insulin activity from a nonbinding precursor. When the role of somatic mutation in the binding of rodent insulin is examined, autoreactivity is associated with single mutations in both Abs. Together these findings indicate that, despite a low mutation frequency, IgG insulin Abs may not be derived directly from germ-line (unmutated) precursors. The requirement for somatic mutation as a prerequisite for measurable insulin binding suggests these Abs have their origin in a previously mutated B cell pool as a consequence of the individual's immune history. Low avidity interaction with endogenous insulin may play a role in selection of these B cells and contribute to the origin of clonal ignorance.

Amino Acid Sequence↗
PubMed2005

Evolution and molecular phylogeny of Listeria monocytogenes isolated from human and animal listeriosis cases and foods.

To probe the evolution and phylogeny of Listeria monocytogenes from defined host species and environments, L. monocytogenes isolates from human (n = 60) and animal (n = 30) listeriosis cases and food samples (n = 30) were randomly selected from a larger collection of isolates (n = 354) obtained in New York State between 1999 and 2001. Partial sequencing of four housekeeping genes (gap, prs, purM, and ribC), one stress response gene (sigB), and two virulence genes (actA and inlA) revealed between 11 (gap) and 33 (inlA) allelic types as well as 52 sequence types (unique combination of allelic types). actA, ribC, and purM demonstrated the highest levels of nucleotide diversity (pi > 0.05). actA and inlA as well as prs and the hypervariable housekeeping genes ribC and purM showed evidence of horizontal gene transfer and recombination. actA and inlA also showed evidence of positive selection at specific amino acid sites. Maximum likelihood phylogenies for all seven genes confirmed that L. monocytogenes contains two deeply separated evolutionary lineages. Lineage I was found to be highly clonal, while lineage II showed greater diversity and evidence of horizontal gene transfer. Allelic types were exclusive to lineages, except for a single gap allele, and nucleotide distance within lineages was much lower than that between lineages, suggesting that genetic exchange between lineages is rare. Our data show that (i) L. monocytogenes is a highly diverse species with at least two distinct phylogenetic lineages differing in their evolutionary history and population structure and (ii) horizontal gene transfer as well as positive selection contributed to the evolution of L. monocytogenes.

Animal Feed↗
PubMed2001

Genetic pathways in the evolution of morphologically distinct colorectal neoplasms.

Colorectal adenomas can be morphologically classified as exophytic or flat. Polypoid cancers and cancers arising de novo (ie., without any adenomatous component) might be the results of genetic progression from exophytic and flat adenomas, respectively. In this study, we examined 94 morphologically distinct neoplastic specimens for mutations in K-RAS and analyzed 10 microsatellite loci tightly linked to the tumor suppressor genes APC, p53, DCC/SMAD4, hMSH2, and hMLH1. K-RAS mutations were significantly associated with exophytic adenomas [11 of 21 (52%)] compared to flat adenomas [2 of 13(15%), P < 0.03] and polypoid cancers [17 of 25 (68%)] compared to cancers arising de novo [7 of 25 (28%), P < 0.01]. Two polypoid cancer cases demonstrated three and four different K-RAS mutations, respectively, suggesting multiple areas of clonal expansion. Cancers arising de novo were significantly associated with loss of heterozygosity (LOH) at chromosome 3p compared to pol ypoid cancers [6 of 18(33%) versus 1 of 20(5%), P < 0.03], whereas the prevalence of LOH at chromosomes 2p, 5q, 17p, and 18q and microsatellite instability were not different between the groups. For all cancers, LOH at chromosomes 17p and 18q occurred in 47 and 51%, respectively. However, LOH at 17p and 18q occurred in 0 and 16% of benign lesions, respectively, suggesting their role in malignant transformation. There was no difference in LOH at chromosomes 17p and 18q between exophytic and flat lesions. These findings suggest that (a) mutant K-RAS is associated with the exophytic growth of colonic neoplasms, and that (b) some colorectal cancers arising de novo lose chromosome 3p during their evolution, which is not seen in polypoid cancers. Half of all cancers lose chromosomes 17p and 18q at or near the malignant transition of benign lesions as reported previously, irrespective of morphology. There may be more than one genetic avenue for colorectal cancer formation, and this correlates with the morphological characteristics.

Adenoma↗
PubMed2005

Clostridium perfringens: insight into virulence evolution and population structure.

Clostridium perfringens is an important pathogen in veterinary and medical fields. Diseases caused by this organism are in many cases life threatening or fatal. At the same time, it is part of the ecological community of the intestinal tract of man and animals. Virulence in this species is not fully understood and it does seem that there is erratic distribution of the toxin/enzyme genes within C. perfringens population. We used the recently developed multiple-locus variable-number tandem repeat analysis (MLVA) scheme to investigate the evolution of virulence and population structure of this species. Analysis of the phylogenetic signal indicates that acquisition of the major toxin genes as well as other plasmid-borne toxin genes is a recent evolutionary event and their maintenance is essentially a function of the selective advantage they confer in certain niches under different conditions. In addition, it indicates the ability of virulent strains to cause disease in different host species. More interestingly, there is evidence that certain normal flora strains are virulent when they gain access to a different host species. Analysis of the population structure indicates that recombination events are the major tool that shapes the population and this panmixia is interrupted by frequent clonal expansion that mostly corresponds to disease processes. The signature of positive selection was detected in alpha toxin gene, suggesting the possibility of adaptive alleles on the other chromosomally encoded determinants. Finally, C. perfringens proved to have a dynamic population and availability of more genome sequences and use of comparative proteomics and animal modeling would provide more insight into the virulence of this organism.

Animals↗
PubMed2006

Evolution of cooperation among tumor cells.

The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.

Biological Evolution↗
PubMed2001

NmeSI restriction-modification system identified by representational difference analysis of a hypervirulent Neisseria meningitidis strain.

Neisseria meningitidis is a gram-negative bacterium that may cause meningitis, sepsis, or both. The increase in the incidence of meningococcal disease in various countries in the past 2 decades is mainly due the genotypically related lineage III meningococci. The chromosomal DNA differences between lineage III strains and non-lineage III strains were identified using representational difference analysis. Thus, a 1.8-kb locus that is specific for lineage III meningococci was identified. The locus contains three open reading frames encoding the NmeSI restriction-modification system. The methyltransferase gene was cloned and expressed in Escherichia coli. Site AGTACT was found to be modified by the enzyme. In conclusion, lineage III strains differ from endemic strains by the presence of a specific restriction-modification system. This restriction-modification system may contribute to the clonal and hypervirulent character of lineage III strains by influencing horizontal gene transfer and transcription.

Amino Acid Sequence↗
PubMed1997

Parity among the randomly amplified polymorphic DNA method, multilocus enzyme electrophoresis, and Southern blot hybridization with the moderately repetitive DNA probe Ca3 for fingerprinting Candida albicans.

Randomly amplified polymorphic DNA (RAPD) analysis, multilocus enzyme electrophoresis (MLEE), and Southern blot hybridization with moderately repetitive DNA probes have emerged as effective fingerprinting methods for the infectious fungus Candida albicans. The three methods have been compared for their capacities to identify identical or highly related isolates, to cluster weakly related isolates, to discriminate between unrelated isolates, and to assess microevolution within a strain. By computing similarity coefficients between 29 isolates from three cities within the continental United States, strong concordance of the results is demonstrated for RAPD analysis, MLEE, and Southern blot hybridization with the moderately repetitive probe Ca3, and weaker concordance of the results is demonstrated for these three fingerprinting methods and Southern blot hybridization with the moderately repetitive probe CARE2. All methods were also demonstrated to be able to resolve microevolution within a strain, with the Ca3 probe exhibiting the greatest resolving power. The strong correlations demonstrated between polymorphic markers assessed by the four independent fingerprinting methods and the nonrandom association between loci demonstrated by RAPD analysis and MLEE provide evidence for strong linkage disequilibrium and a clonal population structure for C. albicans. In addition, a synapomorphic allele, Pep-3A, was found to be present in all members of one of the three clusters discriminated by RAPD analysis, MLEE, and Ca3 fingerprinting, supporting the concordance of the clustering capacities of the three methods, the robustness of the clusters, and the clonal nature of the clusters.

Adaptor Proteins, Vesicular Transport↗
PubMed2026

Methicillin-resistant Staphylococcus aureus (MRSA) infection in hospitalized patients is dominated by community-acquired strains: genomic epidemiological evidence.

OBJECTIVE: This study aimed to systematically investigate the molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus (MRSA) in Ningxia hospitals, to elucidate their genetic evolutionary relationships, and to delineate the genomic and phenotypic profiles of the dominant lineages. METHODS: Clinical isolates of MRSA strains collected between 01/01/2024 and 30/06/2024 were analyzed, employing second-generation gene sequencing technology, combined with MLST and SCCmec typing, along with evaluation of drug resistance and virulence genes. A phylogenetic tree was constructed to analyze strain homology. RESULTS: A total of 74 non-duplicate Staphylococcus aureus strains (67 MRSA and 7 MSSA) were collected. The most common clonal strain was ST59-IVa, accounting for 46.27%. This strain exhibited a high prevalence of resistance genes mecA and blaZ, at 91.04%. All five ST22-IVa strains were found to lack mecA and erm genes but showed &#x3b2;-lactam resistance, while possessing both lukS/F-PV (PVL) and tsst-1 virulence genes, indicating a significant toxicity risk. Genetic evolution analysis revealed that ST3355, ST4513, and ST59 were closely related, all belonging to SCCmec types IVa; the other ST types exhibited mutations at various loci, with ST5 as the central node, resulting in a wider array of ST and SCCmec typing. CONCLUSION: The ST59-IVa clone is the predominant MRSA strain in Ningxia hospitals, exhibiting multidrug resistance and virulence gene profiles consistent with national trends. However, the emergence of hypervirulent ST22-IVa strains with atypical resistance mechanisms warrants increased vigilance. We recommend enhancing the rational use of antibiotics in hospitals and implementing molecular surveillance for these highly virulent strains.

Methicillin-Resistant Staphylococcus aureus↗
PubMedDate not supplied

Conventional cytogenetics and fluorescence in situ hybridization in persistent cytopenias and myelodysplastic syndromes in childhood.

Accurate detection of the abnormal clone in children with persistent cytopenia (PC) may confirm the diagnosis of myelodysplastic syndrome (MDS) and determine prognosis and evolution of the disease. Bone marrow (BM) samples were obtained from 65 children, 11 of which were finally diagnosed as primary or secondary MDS. Ten to 20 G-banded metaphases were analyzed and FISH was performed using a-satellite probes for chromosomes 7 and 8. Conventional cytogenetic analysis (CCA) was successful in 40/65 samples, revealing clonal aberrations in 3 patients with MDS. FISH was successful in all cases, detecting monosomy 7 and trisomy 8 abnormal clones in 5 patients. Abnormalities were identified in 3/6 children with primary MDS and 3/5 with secondary MDS. None of the patients with PC of etiology other than MDS had a clonal abnormality in the BM. The results confirm the high incidence of chromosome abnormalities in childhood MDS and the sensitivity of FISH in detecting minor abnormal clones.

Adolescent↗
PubMed2006

First insights into the evolution of Streptococcus uberis: a multilocus sequence typing scheme that enables investigation of its population biology.

Intramammary infection with Streptococcus uberis is a common cause of bovine mastitis throughout the world. Several procedures to differentiate S. uberis isolates have been proposed. However, all are prone to interlaboratory variation, and none is suitable for the description of the population structure. We describe here the development of a multilocus sequence typing (MLST) scheme for S. uberis to help address these issues. The sequences of seven housekeeping gene fragments from each of 160 United Kingdom milk isolates of S. uberis were determined. Between 5 and 17 alleles were obtained per locus, giving the potential to discriminate between 1.3 x 10(7) sequence types. In this study, 57 sequence types (STs) were identified. Statistical comparisons between the maximum-likelihood trees constructed by using the seven housekeeping gene fragments showed that the congruence was no better than that between each tree and trees of random topology, indicating there had been significant recombination within these loci. The population contained one major lineage (designated the ST-5 complex). This dominated the population, containing 24 STs and representing 112 isolates. The other 33 STs were not assigned to any clonal complex. All of the isolates in the ST-5 lineage carried hasA, a gene that is essential for capsule production. There was no clear association between ST or clonal complex and disease. The S. uberis MLST system offers researchers a valuable tool that allows further investigation of the population biology of this organism and insights into the epidemiology of this disease on a global scale.

Animals↗
PubMed2003

Genome diversification in Staphylococcus aureus: Molecular evolution of a highly variable chromosomal region encoding the Staphylococcal exotoxin-like family of proteins.

Recent genomic studies have revealed extensive variation in natural populations of many pathogenic bacteria. However, the evolutionary processes which contribute to much of this variation remain unclear. A previous whole-genome DNA microarray study identified variation at a large chromosomal region (RD13) of Staphylococcus aureus which encodes a family of proteins with homology to staphylococcal and streptococcal superantigens, designated staphylococcal exotoxin-like (SET) proteins. In the present study, RD13 was found in all 63 S. aureus isolates of divergent clonal, geographic, and disease origins but contained a high level of variation in gene content in different strains. A central variable region which contained from 6 to 10 different set genes, depending on the strain, was identified, and DNA sequence analysis suggests that horizontal gene transfer and recombination have contributed to the diversification of RD13. Phylogenetic analysis based on the RD13 DNA sequence of 18 strains suggested that loss of various set genes has occurred independently several times, in separate lineages of pathogenic S. aureus, providing a model to explain the molecular variation of RD13 in extant strains. In spite of multiple episodes of set deletion, analysis of the ratio of silent substitutions in set genes to amino acid replacements in their products suggests that purifying selection (selective constraint) is acting to maintain SET function. Further, concurrent transcription in vitro of six of the seven set genes in strain COL was detected, indicating that the expression of set genes has been maintained in contemporary strains, and Western immunoblot analysis indicated that multiple SET proteins are expressed during the course of human infections. Overall, we have shown that the chromosomal region RD13 has diversified extensively through episodes of gene deletion and recombination. The coexpression of many set genes and the production of multiple SET proteins during human infection suggests an important role in host-pathogen interactions.

Animals↗