Endonuclease banding reveals that atrazine-induced aneuploidy resembles spontaneous chromosome loss in Crassostrea gigas.

Aneuploidy has previously been observed in the Pacific oyster, Crassostrea gigas, and shown to be negatively correlated with growth. Moreover, a significant impact of atrazine exposure has been described in C. gigas, and persistence of that effect has been observed between generations. Evidence of differential chromosome loss has been demonstrated in aneuploid karyotypes of C. gigas using the G-banding technique. Pairs 1, 5, 9, and 10 are characterized by the loss of 1 chromosome. As restriction enzyme (RE) digestion chromosome banding allows a better identification of chromosome pairs, we used this technique to identify which chromosomes are affected when aneuploidy is increased by exposure to atrazine. The progeny of oysters contaminated by atrazine were analysed using the restriction enzyme HaeIII. The study of 26 RE-banded aneuploid karyotypes showed that the same chromosome pairs (1, 5, 9, and 10) were affected by the loss of 1 chromosome (61%, 15%, 42%, and 42%, respectively). Further investigation is required to enable a better understanding of aneuploidy in oysters, especially with respect to why some chromosomes are more easily lost than others, and why cells tolerate the loss of these chromosomes.     

Chromosomal variations within aneuploid cancer lines.

Aneuploid cancers exhibit a wide spectrum of clinical aggressiveness, possibly because of varying chromosome compositions. To test this, karyotypes from the diploid CCD-34Lu fibroblast and the aneuploid A549 and SUIT-2 cancer lines underwent fluorescence in situ hybridization (FISH) and DAPI counterstaining. The number of DAPI-stained and FISH-identified chromosomes, 1-22, X,Y, as well as structural abnormalities, were counted and compared using the chi(2), Mann-Whitney rank sum test and the Levene's equality of variance. Virtually all of the evaluable diploid CCD-34Lu karyotypes had 46 chromosomes with two normal-appearing homologues. The aneuploid chromosome numbers per karyotype were highly variable, averaging 62 and 72 for the A549 and SUIT-2 lines, respectively. However, the A549 chromosome numbers were more narrowly distributed than the SUIT-2 karyotype chromosome numbers. Furthermore, 25% of the A549 chromosomes had structural abnormalities compared to only 7% of the SUIT-2 chromosomes. The chromosomal compositions of the aneuploid A549 and SUIT-2 cancer lines are widely divergent, suggesting that diverse genetic alterations, rather than chance, may govern the chromosome makeups of aneuploid cancers.     

Etude de l'aneuploïdie dans différents naissains d'Ostreidae (Bivalvia)

Study of aneuploidy in spats of Ostreidae (Bivalvia). Chromosomes of cells from gill tissue of juveniles (5–10 mm) from four different populations of Ostrea edulis and five different populations of Crassostrea gigas were examined in order to study aneuploidy and its significance. Mitotic chromosome counts were made for a sample of spats in each population. Cells with the normal diploid complement (2n=20) and with aneuploid complements (2n different from 20) were scored. The total percentage of aneuploid cells in the studied populations of the two species varies from 9% to 34%. Individual patterns of aneuploidy were examined in three populations of Crassostrea gigas. Some animals showed only normal diploid cells, others having both normal and aneuploid cells in variable proportions. The relationship between aneuploidy and growth rate was studied in experimental spats. Mitotic chromosome counts were made on individuals from two groups of animals: the first group was collected at a precise date at a control size of 8 mm, the second group reaching the same size of 8 mm only one month later. The percentage of animals showing aneuploid cells is much greater in the second group. There is a relationship between occurrence of aneuploid cells and growth rate. The karyotypes of 18 aneuploid sets of Ostrea edulis from different spats were analyzed. Chromosome loss was observed only in the submetacentric chromosome pairs. This loss of chromosomes could have an effect on the percentage of homozygotes observed in electrophoregrams. Thus, the percentage of homozygotes would be higher in juveniles showing the greatest number of aneuploid cells. An excess of homozygosity (=heterozygote deficiency) has been reported at a number of enzyme loci in over two dozen bivalve species (including Ostrea and Crassostrea). We suggest the hypothesis that this excess of homozygosity could be related to the occurrence of aneuploid cells. The relationship between aneuploidy and growth rate may prove to be a genetic factor of importance for oyster culturing.     

Clone heterogeneity in diploid and aneuploid breast carcinomas as detected by FISH

We investigated the relationship between DNA ploidy and alterations in chromosomes 1, 8, 12, 16, 17, and 18 in 63 breast carcinoma samples by static cytofluorometry and fluorescence in situ hybridization. Thirty specimens were diploid and 33 were aneuploid. In aneuploid samples, the DNA index value ranged from 1.3 to 3.1, with a main peak near tetraploid values. Diploid clones were present in 21 of 33 aneuploid specimens. Fluorescence in situ hybridization analysis showed a heterogeneous degree of alterations in diploid specimens: one sample was normal, 16 samples had one to three chromosome alterations involving mostly chromosomes 1, 16, and 17, and 13 samples an even higher degree of alterations. The 33 aneuploid specimens showed a very high number of signals (four, five, or more). All the investigated chromosomes were affected in 23 of 33 specimens. Alterations in chromosomes 1 and 17 were detected to a similar percentage in diploid and aneuploid samples, whereas chromosome 16 monosomy was more frequent in diploid samples. Overrepresentation of chromosomes 8, 12, 16, and 18 was significantly higher in aneuploid than in diploid samples. Based on these results, we suggest that diploid and aneuploid breast carcinomas are genetically related. Chromosome 1 and 17 alterations and chromosome 16 monosomy are early changes. Allelic and chromosomal accumulations occur during progression of breast carcinoma by different mechanisms. The high clone heterogeneity found in 17 of 33 aneuploid samples could not be completely explained by endoreduplication and led to the suggestion that chromosomal instability concurs with aneuploidy development. This different evolutionary pathway might be clinically relevant because clone heterogeneity might cause metastasis development and resistance to therapy.     

Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes

Most tumors have abnormal karyotypes, which arise from mistakes during mitotic division of healthy euploid cells and evolve through numerous complex mechanisms. In a recent mouse model with increased chromosome missegregation, chromosome gains dominate over losses both in pretumor and tumor tissues, whereas T-cell lymphomas are characterized by gains of chromosomes 14 and 15. However, the quantitative understanding of clonal selection leading to tumor karyotype evolution remains unknown. Here we show, by introducing a mathematical model based on a concept of a macro-karyotype, that tumor karyotypes can be explained by proliferation-driven evolution of aneuploid cells. In pretumor cells, increased apoptosis and slower proliferation of cells with monosomies lead to predominant chromosome gains over losses. Tumor karyotypes with gain of one chromosome can be explained by karyotype-dependent proliferation, whereas, for those with two chromosomes, an interplay with karyotype-dependent apoptosis is an additional possible pathway. Thus, evolution of tumor-specific karyotypes requires proliferative advantage of specific aneuploid karyotypes.     

Chromosome abnormalities in newborn children. Physical aspects

Summary A chromosome examination was made on 11,148 consecutively live-born children: 93 had a chromosome abnormality and 192 a chromosome variant. The physical aspects of the children with chromosome abnormalities and variants were compared with those of the children with normal karyotypes. Children with aneuploid or unbalanced chromosome abnormalities were more frequently immature or not fully developed at birth than those with normal karyotypes. Birth weight was lower in children with all types of chromosome abnormalities, including reciprocal translocations and chromosome variants. The low birth weight in children with chromosome variants was mainly due to the low birth weight of children with G variants. These children were also subject to a higher frequency of special delivery treatment. Heart disorders were increased in children with aneuploid or unbalanced chromosome abnormalities. The frequency of foetal erythroblastosis was increased in children with short Y as well as in children with acentric fragments. Neonatal mortality was higher in children with aneuploid or unbalanced chromosome abnormalities than in children with normal karyotypes.     

The cytogenetic structure of Vicia sativa aggregate

Summary The cytogenetic structure of Vicia sativa aneuploid series was assessed by examination of the chromosome pairing in hybrids between types having 2n = 10, 2n = 12 and 2n = 14. Two different karyotypes were distinguished at both the 2n = 10 and 2n = 12 levels. Chromosome pairing in hybrids involved two 2n = 10 karyotypes, indicating that the parental lines differed by two translocations. A similar indication was obtained for the two 2n = 12 karyotypes employed. The meiotic behavior of the 2n = 10 x 2n = 12 hybrids indicated that the parental lines differed by up to three translocations, some of which involved unequal chromosome segments. It has been proposed that the 2n = 10 types were developed from the 2n = 12 via centric or tandem fusion and additional rearrangements further accelerated chromosome repatterning at the two 2n levels. Hybrids between the 2n = 14 V. sativa and the former 2n types had very irregular chromosome pairing and were highly sterile. It has been proposed that the 2n = 14 type is a relatively new evolvement in V. sativa because of its shorter complement in comparison with the other karyotypes. The subterraneous pods of the 2n = 14 type, a characteristic which is absent in other V. sativa types and in the entire genus Vicia, also supports an advanced, phylogenetic position. The 2n = 14 type probably arose from n = 7 gametes produced by the 2n= 12 x 2n = 10 hybrid and the establishment of the row 2n = 14 type was acquired through conspicuous chromosome deletions. In spite of its remarkable chromosomal variation, V. sativa can still be considered, for breeding purposes, as being one gene pool. The wild forms of V. sativa can thus be valuable sources for improving the cultivated vetch.     

Mosaic aneuploidy in early fetal losses

Chromosomal mosaicism is the presence of 2 or more cell lines with different karyotypes in the same individual. Mosaic karyotypes are a remarkable feature of early stages of human embryo development. They result from mitotic errors in chromosome segregation and demonstrate the clearest example of somatic mutagenesis in human beings. This review is devoted to the classification of chromosomal mosaicism and the analysis of its underlying mechanisms, incidence and phenotypic effects during embryo development. A model for tissue-specific aneuploid cell line compartmentalization in spontaneous abortions is introduced.     

Characterisation and genetic polymorphism of metallothionein gene CgMT4 in experimental families of Pacific oyster Crassostrea gigas displaying summer mortality

Summer mortality events have been observed in Pacific oyster Crassostrea gigas for several decades. This paper examines the selective pressure exerted by summer mortality on the polymorphism of a newly identified oyster metallothionein gene. CgMT4 cDNA and genomic sequences were obtained. CgMT4 was studied in two generations of oysters reared in three sites on the French Atlantic coast, using single strand conformation polymorphism analysis. Four alleles were detected. Individuals carrying genotype MT4-CD seem to have higher susceptibility to summer risk conditions. The MT4 gene could be a potential new genetic marker for susceptibility; further validation studies are recommended.     

Differences in the rDNA-bearing chromosome divide the Asian-Pacific and Atlantic species of Crassostrea (Bivalvia, Mollusca)

Karyotype and chromosomal location of the major ribosomal RNA genes (rDNA) were studied using fluorescence in situ hybridization (FISH) in five species of CRASSOSTREA: three Asian-Pacific species (C. gigas, C. plicatula, and C. ariakensis) and two Atlantic species (C. virginica and C. rhizophorae). FISH probes were made by PCR amplification of the intergenic transcribed spacer between the 18S and 5.8S rRNA genes, and labeled with digoxigenin-11-dUTP. All five species had a haploid number of 10 chromosomes. The Atlantic species had 1-2 submetacentric chromosomes, while the three Pacific species had none. FISH with metaphase chromosomes detected a single telomeric locus for rDNA in all five species without any variation. In all three Pacific species, rDNA was located on the long arm of Chromosome 10 (10q)--the smallest chromosome. In the two Atlantic species, rDNA was located on the short arm of Chromosome 2 (2p)--the second longest chromosome. A review of other studies reveals the same distribution of NOR sites (putative rDNA loci) in three other species: on 10q in C. sikamea and C. angulata from the Pacific Ocean and on 2p in C. gasar from the western Atlantic. All data support the conclusion that differences in size and shape of the rDNA-bearing chromosome represent a major divide between Asian-Pacific and Atlantic species of CRASSOSTREA: This finding suggests that chromosomal divergence can occur under seemingly conserved karyotypes and may play a role in reproductive isolation and speciation.     

Chromosome inheritance in triploid Pacific oyster Crassostrea gigas Thunberg

Reproduction and chromosome inheritance in triploid Pacific oyster (Crassostrea gigas Thunberg) were studied in diploid female x triploid male (DT) and reciprocal (TD) crosses. Relative fecundity of triploid females was 13.4% of normal diploids. Cumulative survival from fertilized eggs to spat stage was 0.007% for DT crosses and 0.314% for TD crosses. Chromosome number analysis was conducted on surviving progeny from DT and TD crosses at 1 and 4 years of age. At Year 1, oysters from DT crosses consisted of 15% diploids (2n=20) and 85% aneuploids. In contrast, oysters from TD crosses consisted of 57.2% diploids, 30.9% triploids (3n=30) and only 11.9% aneuploids, suggesting that triploid females produced more euploid gametes and viable progeny than triploid males. Viable aneuploid chromosome numbers included 2n+1, 2n+2, 2n+3, 3n-2 and 3n-1. There was little change over time in the overall frequency of diploids, triploids and aneuploids. Among aneuploids, oysters with 2n+3 and 3n-2 chromosomes were observed at Year 1, but absent at Year 4. Triploid progeny were significantly larger than diploids by 79% in whole body weight and 98% in meat weight at 4 years of age. Aneuploids were significantly smaller than normal diploids. This study suggests that triploid Pacific oyster is not completely sterile and cannot offer complete containment of cultured populations.     

Observations of de novo clones of cytogentically aberrant cells in primary fibroblast cell strains from phenotypically normal women.

In a recent study of chromosome breakage frequencies in 36 primary fibroblast cell strains derived from skin from 10 phenotypically normal women, we observed seven different clones of cells having consistent chromosomal abnormalities. Five of the stem lines were noted in cultures from "control" women and two in fibroblasts from women taking oral contraceptives. We observed aneuploid clones as well as stem lines bearing structural abnormalities (e.g., translocation, inversions). The various aberrant clones were found in cultures ranging in age from 41 to 144 days and comprised varying percentages of the cell populations ranging from 0.8% to virtually 100%. The possible evolution in culture of clones of cells having aberrant karyotypes should be considered in interpreting findings from fibroblast cultures initiated for clinical evaluation.     

Frequency and distribution of chromosome abnormalities in human spermatozoa

This study reviews the frequency and distribution of numerical and structural chromosomal abnormalities in spermatozoa from normal men obtained by the human-hamster system and by multicolor-FISH analysis on decondensed sperm nuclei. Results from large sperm karyotyping series analyzed by chromosome banding techniques and results from multicolor FISH in sperm nuclei (of at least 10(4) spermatozoa per donor and per probe) were reviewed in order to establish baseline values of the sperm chromosome abnormalities in normal men. In karyotyping studies, the mean disomy frequency in human sperm is 0.03% for each of the autosomes, and 0.11% for the sex chromosomes, lower than those reported in sperm nuclei by FISH studies using a similar methodology (0.09% and 0.26%, respectively). Both types of studies coincide in that chromosome 21 and sex chromosomes have a greater tendency to suffer segregation errors than the rest of the autosomes. The mean incidence of diploidy, only available from multicolor FISH in sperm nuclei, is 0.19%. Inter-donor differences observed for disomy and diploidy frequencies among FISH studies of decondensed sperm nuclei using a similar methodology could reflect real differences among normal men, but they could also reflect the subjective application of the scoring criteria among laboratories. The mean frequency of structural aberrations in sperm karyotypes is 6.6%, including all chromosome types of abnormalities. Chromosome 9 shows a high susceptibility to be broken and 50% of the breakpoints are located in 9q, between the centromere and the 9qh+ region. Structural chromosome aberrations for chromosomes 1 and 9 have also been analyzed in human sperm nuclei by multicolor FISH. Unfortunately, this assay does not allow to determine the specific type of structural aberrations observed in sperm nuclei. An association between advancing donor age and increased frequency of numerical and structural chromosome abnormalities has been reported in spermatozoa of normal men.     

Checkpoint-independent stabilization of kinetochore-microtubule attachments by Mad2 in human cells

Faithful chromosome segregation is required for cell and organism viability and relies on both the mitotic checkpoint and the machinery that corrects kinetochore-microtubule (k-MT) attachment errors. Most solid tumors have aneuploid karyotypes and many missegregate chromosomes at high rates in a phenomenon called chromosomal instability (CIN). Mad2 is essential for mitotic checkpoint function and is frequently overexpressed in human tumors that are CIN. For unknown reasons, cells overexpressing Mad2 display high rates of lagging chromosomes. Here, we explore this phenomenon and show that k-MT attachments are hyperstabilized by Mad2 overexpression and that this undermines the efficiency of correction of k-MT attachment errors. Mad2 affects k-MT attachment stability independently of the mitotic checkpoint because k-MT attachments are unaltered upon Mad1 depletion and Mad2 overexpression hyperstabilizes k-MT attachments in Mad1-deficient cells. Mad2 mediates these effects with Cdc20 by altering the centromeric localization and activity of Aurora B kinase, a known regulator of k-MT attachment stability. These data reveal a new function for Mad2 to stabilize k-MT attachments independent of the checkpoint and explain why Mad2 overexpression increases chromosome missegregation to cause chromosomal instability in human tumors.     

Possible causes of chromosome instability: comparison of chromosomal abnormalities in cancer cell lines with mutations in BRCA1, BRCA2, CHK2 and BUB1

A large proportion of epithelial cancers show the chromosome-instability phenotype, in which they have many chromosome abnormalities. This is thought to be the result of mutations that disrupt chromosome maintenance, but the causative mutations are not known. We identified cell lines known to have mutations that might cause chromosome instability, and examined their karyotypes. Two cell lines, the breast cancer line HCC1937 and the pancreatic cancer line CAPAN-1, that have mutations respectively in BRCA1 and BRCA2, had very abnormal karyotypes, with many structural and numerical chromosome changes and substantial variation between metaphases. However, two colorectal cancer lines with mutations in BUB1, a spindle checkpoint protein involved in chromosome segregation, had rather simple near-tetraploid karyotypes, with minimal loss or gain of chromosomes other than the endoreduplication event, and minimal structural change. Apart from tetraploidy, these karyotypes were typical of colorectal lines considered to be chromosomally stable. Two lines derived from the same tumour, DLD-1 and HCT-15, with bi-allelic mutation of CHK2, had karyotypes that were typical of near-diploid colorectal lines considered chromosomally stable. The karyotypes observed supported the proposed role for BRCA1 and BRCA2 mutations in chromosomal instability, but showed that the tested mutations in BUB1 and CHK2 did not result in karyotypes that would have been predicted if they were sufficient for chromosomal instability.     

Variations of Candida albicans electrophoretic karyotypes.

We previously described 14 rare spontaneous morphological mutants of Candida albicans that were associated with chromosomal aberrations (E. P. Rustchenko-Bulgac, F. Sherman, and J. B. Hicks, J. Bacteriol. 172:1276-1283, 1990). Improved conditions for separation of chromosomes, as well as hybridization probes, were used to investigate the variation of karyotypes of clinical isolates and additional morphological mutants. All 23 newly analyzed morphological mutants, representing frequently occurring and highly unstable colonial forms, had a variety of altered karyotypes. All chromosomal changes were similar to those previously observed in mutants m1 to m14. In this study, I particularly noted that the most frequent changes involved the long chromosome VIII, which carries ribosomal DNA cistrons. Two rates of instability were uncovered by analyzing the progenies from two highly unstable mutants. An unstable mutant proved to be able to continuously produce a large number of altered karyotypes that could result in a wide variety of different phenotypes. Furthermore, all four independent clinical isolates, FC18, C9, 3153A, and WO-1, common laboratory strains, revealed different electrophoretic karyotypes and distinct colonial morphologies on a synthetic medium, similar to spontaneous mutants. The differences of electrophoretic karyotypes observed among clinical isolates resembled the changes found among different kinds of spontaneous morphological mutants. These findings contribute to the understanding of natural karyotypic variability and are in agreement with the hypothesis that chromosomal alterations observed spontaneously under laboratory conditions provide this amictic species with genetic variability in nature.     

Chromosomal organization of simple sequence repeats in the Pacific oyster (<Emphasis Type="Italic">Crassostrea gigas</Emphasis>): (GGAT)<Subscript>4</Subscript>, (GT)<Subscript>7</Subscript> and (TA)<Subscript>10</Subscript> chromosome patterns

Chromosome identification is essential in oyster genomic research. Fluorescence in situ hybridization (FISH) offers new opportunities for the identification of oyster chromosomes. It has been used to locate satellite DNAs, telomeres or ribosomal DNA sequences. However, regarding chromosome identification, no study has been conducted with simple sequence repeats (SSRs). FISH was used to probe the physical organization of three particular SSRs, (GGAT)(4), (GT)(7) and (TA)(10) onto metaphase chromosomes of the Pacific oyster, Crassostrea gigas. Hybridization signals were observed in all the SSR probes, but the distribution and intensity of signals varied according to the oligonucleotide repeat. The intercalary, centromeric and telomeric bands were observed along the chromosomes, and for each particular repeat every chromosome pair presented a similar pattern, allowing karyotypic analysis with all the SSRs tested. Our study is the first in mollusks to show the application of SSR in situ hybridization for chromosome identification and karyotyping. This technique can be a useful tool for oyster comparative studies and to understand genome organization in different oyster taxa.     

Cytotaxonomy of the apocynaceae

At present there is karyological information on ca 10% of the species and ca 30% of the genera of the Apocynaceae. Basic numbers of x = 6, 8, 9, 10, 11, 12, 16, 18, 20, 21 and 23 have been assessed. Of these x = 11 is primitive, occurring in ca 60% of the genera. Those of x = 6, 8, 9 and 10 have evolved by reduction, and x = 12 by increase from x = 11. In the subtribe Secondatiinae however, x = 12 is most likely the result of doubling x = 6. The numbers x = 16, 18 and 20 are likewise doubles of x = 8, 9 and 10 respectively. Those of x = 21, 23, and in one case, x = 20 are probably aneuploid products of doubles of x = 11. The two larger subfamilies, Plumerioideae and Apocynoideae have the basic numbers x = 8, 9, 10 and 11 in common and are not separable on the basis of chromosomal evidence. The third small subfamily Cerberoideae is more homogeneous according to basic number, i.e. x = 10 and 20. Most genera are characterized by a constant basic number, but some have two basic numbers; these clearly are cases of infrageneric aneuploidy. Based on records in the literature two closely related generaApocynum andTrachomitum appear to be characterized by a basic number of x = 8 as well as x = 11. This conflicting situation should be clarified by further karyological research. From the level of subtribe onwards some taxa have one basic number, but others are characterized by two or more numbers. The occurrence of similar basic numbers in different phylads of the family is considered to be the result of similar chromosomal evolution mechanisms. Approximately 22% of the investigated species are polyploid. Intrageneric polyploidy occurs with a frequency of about 12.5% and infraspecific polyploidy with less than 4%. The karyotypes observed are symmetrical: the chromosomes within a karyotype are similar in length with primary constrictions usually in a median position. In the Tabernaemontaneae however, it was observed that the karyotypes comprise one pair of distinctly heterobrachial chromosomes in addition to the metacentric ones. This tribe is also characterized by chromosomes which are relatively long. Most genera of the African continent, which are well known regarding their chromosome number, are characterized by x = 11. Exceptions areStrophantus (x = 9) with a mainly tropical African distribution. Two other genera with derived numbers, i.e.Gonioma with x = 10 andPachypodium with x = 9, occur in southern Africa and Madagascar. The genera with a non-African distribution are less known for their chromosome number. However, the available evidence suggests that evolution of derived numbers has occurred more frequently outside Africa than on this continent.     

Aneuploidy, the primary cause of the multilateral genomic instability of neoplastic and preneoplastic cells

Cancers have a clonal origin, yet their chromosomes and genes are non-clonal or heterogeneous due to an inherent genomic instability. However, the cause of this genomic instability is still debated. One theory postulates that mutations in genes that are involved in DNA repair and in chromosome segregation are the primary causes of this instability. But there are neither consistent correlations nor is there functional proof for the mutation theory. Here we propose aneuploidy, an abnormal number of chromosomes, as the primary cause of the genomic instability of neoplastic and preneoplastic cells. Aneuploidy destabilizes the karyotype and thus the species, independent of mutation, because it corrupts highly conserved teams of proteins that segregate, synthesize and repair chromosomes. Likewise it destabilizes genes. The theory explains 12 of 12 specific features of genomic instability: (1) Mutagenic and non-mutagenic carcinogens induce genomic instability via aneuploidy. (2) Aneuploidy coincides and segregates with preneoplastic and neoplastic genomic instability. (3) Phenotypes of genomically unstable cells change and even revert at high rates, compared to those of diploid cells, via aneuploidy-catalyzed chromosome rearrangements. (4) Idiosyncratic features of cancers, like immortality and drug-resistance, derive from subspecies within the 'polyphyletic' diversity of individual cancers. (5) Instability is proportional to the degree of aneuploidy. (6) Multilateral chromosomal and genetic instabilities typically coincide, because aneuploidy corrupts multiple targets simultaneously. (7) Gene mutation is common, but neither consistent nor clonal in cancer cells as predicted by the aneuploidy theory. (8) Cancers fall into a near-diploid (2 N) class of low instability, a near 1.5 N class of high instability, or a near 3 N class of very high instability, because aneuploid fitness is maximized either by minimally unstable karyotypes or by maximally unstable, but adaptable karyotypes. (9) Dominant phenotypes, because of aneuploid genotypes. (10) Uncertain developmental phenotypes of Down and other aneuploidy syndromes, because supply-sensitive, diploid programs are destabilized by products from aneuploid genes supplied at abnormal concentrations; the maternal age-bias for Down's would reflect age-dependent defects of the spindle apparatus of oocytes. (11) Non-selective phenotypes, e.g., metastasis, because of linkage with selective phenotypes on the same chromosomes. (12) The target, induction of genomic instability, is several 1000-fold bigger than gene mutation, because it is entire chromosomes. The mutation theory explains only a few of these features. We conclude that the transition of stable diploid to unstable aneuploid cell species is the primary cause of preneoplastic and neoplastic genomic instability and of cancer, and that mutations are secondary.     

Condition-specific competition allows coexistence of competitively superior exotic oysters with native oysters

1. Trade-offs between competitive ability and tolerance of abiotic stress are widespread in the literature. Thus, condition-specific competition may explain spatial variability in the success of some biological invaders and why, in environments where there is small-scale environmental variability, competitively inferior and superior species can coexist. 2. We tested the hypothesis that differences in abiotic stress alter the outcome of competitive interactions between the native Sydney rock oysters Saccostrea glomerata and exotic Pacific oysters Crassostrea gigas by experimentally testing patterns of intra- and interspecific competition across a tidal elevation gradient of abiotic stress at three sites on the east coast of Australia. 3. At low and mid-intertidal heights, exotic C. gigas were able to rapidly overgrow and smother native S. glomerata, which grew at c. 60% of the exotic's rate. In high intertidal areas, where C. gigas displayed about 80% mortality but similar growth rates to S. glomerata, the native oyster was not affected by the presence of the exotic species. 4. Asymmetrical effects of the exotic species on the native could not be replicated by manipulating densities of conspecifics, confirming that effects at low and mid-intertidal heights were due to interspecific competition. 5. Our results suggest that the more rapid growth of C. gigas than S. glomerata comes at the cost of higher mortality under conditions of abiotic stress. Thus, although C. gigas may rapidly overgrow S. glomerata at low and mid tidal heights, the native oyster will not be competitively excluded by the exotic due to release from competition at high intertidal elevations. 6. The success of trade-offs in explaining spatial variation in the outcome of competitive interactions between C. gigas and S. glomerata strengthen the claim that these may be a useful tool in the quest to produce general predictive models of invasion success.