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PubMed2005

On sexual behavior and sex-role reversal.

Sex is not about reproduction; sex is about (re-)combination of DNA. Sex, not reproduction, always involves physical contact between two individuals; to achieve this, strategies of sexual behavior evolved. Sexual behavior, therefore, did not evolve as part of a reproductive strategy, but evolved to enable exchange of genetic material. In multicellular organisms the situation is more complicated than in unicellular organisms, as it is impossible for each cell within a multicellular body to have sex with another cell. Hence, evolution selected a system in which the possibility to have sex was limited to only one cell-line: the germ cells. As a result, sex adopted the character of fertilization, and sex and reproduction became inseparably linked. Still, in some species, including humans, sexual behavior still exhibits features of its evolutionary past: in humans (like in bonobo's) most sexual activity and many sexual behavioral patterns have nothing to do with reproduction (masturbation, homosexual behavior, for example); in humans, sexual behavior also became associated with other strategic objectives, such as intensifying the pair bond, expression of love or power. Different genders - male and female - evolved, and each gender evolved typical gender-related sexual and reproductive strategies as well. In most multicellular species, these strategies became inextricably mixed, and sexual behavior increasingly more - and in most species even exclusively - 'served' the interests of reproduction: sexual behavior became more or less synonymous with reproductive behavior. In most species, the 'mix' of sexual and reproductive strategies evolved into typical gender-related patterns of behavior, that is, in typical 'sex-roles'. Often, males are bigger and more 'beautiful' (= more intensely ornamented) than females; males compete with each other for access to females; males court females, while females choose males ('female choice'). However, ecological circumstances may cause a reversal of sex-roles, resulting in a situation in which females are bigger and more intensely ornamented than males, females compete for access to males, females court males and only males invest in care for the young, provided they are relatively certain of their paternity. Also, as in the case of the spotted hyena, females may be highly virilized and be socially dominant. This 'sex-role reversal' is seen, e.g., when males are relatively rare due to high predation pressure, or when the process of reproduction is very risky for the same reason: then it is 'better' that males, with their plenty of sperm, are wasted, than females with their few, precious eggs. It can be argued, with women being the fair sex, exhibiting competitive behavior and with an actively displaying courtship, and with men investing heavily in their offspring, meanwhile taking all (cultural) kinds of measures to guarantee their paternity, that humans, too, exhibit some degree of sex-role reversal.

Animals↗
PubMedDate not supplied

Importance of calcium to the regulation of polymorphism in Wangiella (Exophiala) dermatitidis.

Critical steps implicated in the polymorphism of Wangiella dermatitidis were found to be sensitive to calcium ion availability. When grown in a defined, synthetic medium under various pH and temperature conditions, two thresholds of calcium ion concentrations were identified: a lower concentration favouring non-polarized growth leading to multicellular form development and a higher concentration promoting polarized growth characterized by yeast budding or pseudo/true hyphal growth. The phenotypic transition of yeasts to multicellular forms or to hyphae was induced at both 25 and 37 degrees C in the wild-type strain by the addition of calcium to the synthetic medium adjusted to pH 2.5, which was otherwise not conducive to the production of either growth form. However, the calcium additions did not allow maintenance of polarized growth of yeasts or hyphae in a temperature-sensitive, cell-division-cycle mutant (wdcdc2) derived from the same strain and grown at 37 degrees C in the same medium adjusted to either pH 2.5 or 6.5. Instead these conditions allowed only the nonpolarized, multicellular form development associated with this conditional mutant cultured in rich media at the 37 degree C restrictive temperature for yeast bud formation. Results from experiments using the calcium chelator EGTA added to the synthetic medium supported these conclusions at neutral pH with both the wild type and the wdcdc2 mutant cultured at 37 degrees C. The results suggested that during infection different concentrations of calcium may be encountered by W. dermatitidis in different tissues, which might directly regulate its growth and polymorphism and indirectly its virulence depending on host conditions.

Benzenesulfonates↗
PubMed2001

Proliferating cell nuclear antigen (PCNA): ringmaster of the genome.

Proliferating cell nuclear antigen (PCNA) protein is one of the central molecules responsible for decisions of life and death of the cell. The PCNA gene is induced by p53, while PCNA protein interacts with p53-controlled proteins Gadd45, MyD118, CR6 and, most importantly, p21, in the process of deciding cell fate. If PCNA protein is present in abundance in the cell in the absence of p53, DNA replication occurs. On the other hand, if PCNA protein levels are high in the cell in the presence of p53, DNA repair takes place. If PCNA is rendered non-functional or is absent or present in low quantities in the cell, apoptosis occurs. The evolution from prokaryotes to eukaryotes involved a change of function of PCNA from a 'simple' sliding clamp protein of the DNA polymerase complex to an executive molecule controlling critical cellular decision pathways. The evolution of multicellular organisms led to the development of multicellular processes such as differentiation, senescence and apoptosis. PCNA, already an essential molecule in the life of single cellular organisms, then became a protein critical for the survival of multicellular organisms.

Amino Acid Sequence↗
PubMed2005

Engineering lipid vesicles of enhanced intratumoral transport capabilities: correlating liposome characteristics with penetration into human prostate tumor spheroids.

Liposomes have been widely used delivery systems, particularly relevant to the development of cancer therapeutics. Numerous liposome-based drugs are in the clinic or in clinical trials today against multiple tumor types; however, systematic studies of liposome interactions with solid or metastatic tumor nodules are scarce. This study is describing the in vitro interaction between liposomes and avascular human prostate (LNCaP-LN3) tumor spheroids. The ability of fluorescently labelled liposomal delivery systems of varying physicochemical characteristics to penetrate within multicellular tumor spheroids has been investigated by confocal laser scanning microscopy. A variety of liposome characteristics and experimental parameters were investigated, including lipid bilayer composition, duration of liposome-spheroid interaction, mean liposome size, steric stabilization of liposomes. Electrostatic binding between cationic liposomes and spheroids was very efficient; however, it impeded any significant penetration of the vesicles within deeper layers of the tumor spheroid. Small unilamellar liposomes of neutral surface character did not bind as efficiently but exhibited enhanced penetrative transport capabilities closer to the tumor core. Polymer-coated (sterically stabilised) liposomes exhibited almost no interaction with the spheroid, indicating that their limited diffusion within avascular tissues may be a limiting step for their use against micrometastases. Multicellular tumor spheroids were used as models of solid tumor interstitium relevant to delivery systems able to extravasate from the microcapillaries or as models of prevascularized micrometastases. This study illustrates that interactions between liposomes and other drug delivery systems with multicellular tumor spheroids can offer critically important information with respect to optimizing solid or micrometastatic tumor delivery and targeting strategies.

Humans↗
PubMed1989

Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix.

The angiogenic factor, basic fibroblast growth factor (FGF), either stimulates endothelial cell growth or promotes capillary differentiation depending upon the microenvironment in which it acts. Analysis of various in vitro models of spontaneous angiogenesis, in combination with time-lapse cinematography, demonstrated that capillary tube formation was greatly facilitated by promoting multicellular retraction and cell elevation above the surface of the rigid culture dish or by culturing endothelial cells on malleable extracellular matrix (ECM) substrata. These observations suggested to us that mechanical (i.e., tension-dependent) interactions between endothelial cells and ECM may serve to regulate capillary development. To test this hypothesis, FGF-stimulated endothelial cells were grown in chemically defined medium on bacteriological (nonadhesive) dishes that were precoated with different densities of fibronectin. Extensive cell spreading and growth were promoted by fibronectin coating densities that were highly adhesive (greater than 500 ng/cm2), whereas cell rounding, detachment, and loss of viability were observed on dishes coated with low fibronectin concentrations (less than 100 ng/cm2). Intermediate fibronectin coating densities (100-500 ng/cm2) promoted cell extension, but they could not completely resist cell tractional forces. Partial retraction of multicellular aggregates resulted in cell shortening, cessation of growth, and formation of branching tubular networks within 24-48 h. Multicellular retraction and subsequent tube formation also could be elicited on highly adhesive dishes by overcoming the mechanical resistance of the substratum using higher cell plating numbers. Dishes coated with varying concentrations of type IV collagen or gelatin produced similar results. These results suggest that ECM components may act locally to regulate the growth and pattern-regulating actions of soluble FGF based upon their ability to resist cell-generated mechanical loads. Thus, we propose that FGF-stimulated endothelial cells may be "switched" between growth, differentiation, and involution modes during angiogenesis by altering the adhesivity or mechanical integrity of their ECM.

Animals↗
PubMed1991

The distribution of myosin II in Dictyostelium discoideum slug cells.

While the role of myosin II in muscle contraction has been well characterized, less is known about the role of myosin II in non-muscle cells. Recent molecular genetic experiments on Dictyostelium discoideum show that myosin II is necessary for cytokinesis and multicellular development. Here we use immunofluorescence microscopy with monoclonal and polyclonal antimyosin antibodies to visualize myosin II in cells of the multicellular D. discoideum slug. A subpopulation of peripheral and anterior cells label brightly with antimyosin II antibodies, and many of these cells display a polarized intracellular distribution of myosin II. Other cells in the slug label less brightly and their cytoplasm displays a more homogeneous distribution of myosin II. These results provide insight into cell motility within a three-dimensional tissue and they are discussed in relation to the possible roles of myosin II in multicellular development.

Animals↗
PubMed1995

Massive programmed cell death in intestinal epithelial cells induced by three-dimensional growth conditions: suppression by mutant c-H-ras oncogene expression.

Deregulation of molecular pathways controlling cell survival and death, including programmed cell death, are thought to be important factors in tumor formation, disease progression, and response to therapy. Studies devoted to analyzing the role of programmed cell death in cancer have been carried out primarily using conventional monolayer cell culture systems. However the majority of cancers grow as three-dimensional solid tumors. Because gene expression, and possibly function, can be significantly altered under such conditions, we decided to analyze the control and characteristics of cell death using a compatible three-dimensional tissue culture system (multicellular spheroids) and compare the results obtained to those using two-dimensional monolayer cell culture. To do so we selected for study an immortalized, but nontumorigenic line of rat intestinal epithelial cells, called IEC-18, and several tumorigenic variants of IEC-18 obtained by transfection with a mutant (activated) c-H-ras oncogene. The rationale for choosing these cell lines was based in part on the fact that intestinal epithelial cells grow in vivo in a monolayer-like manner and form solid tumors only after sustaining certain genetic mutations, including those involving the ras gene family. We found that the IEC-18 cells, which grow readily and survive in monolayer cell culture, undergo massive cell death within 48-72 h when cultured as multicellular spheroids on a nonadhesive surface. This process was accompanied by a number of features associated with programmed cell death including chromatin condensation (Hoechst 33258 staining) apoptotic morphology, DNA degradation, and a virtual complete loss of colony forming (clonogenic) ability in the absence of apparent membrane damage as well as accumulation of lipid containing vacuoles in the cytoplasm. Moreover, enforced over-expression of a transfected bcl-2 gene could prevent this cell death process from taking place. In marked contrast, three different stably transfected ras clones of IEC-18 survived when grown as multicellular spheroids. In addition, an IEC cell line (called clone 25) carrying its mutant transfected ras under a glucocorticoid inducible promoter survived in three-dimensional culture only when the cells were exposed to dexamethasone. If exposure to dexamethasone was delayed for as long as 48 h the cells nevertheless survived, whereas the cells became irreversibly committed to programmed cell death (PCD) if exposed to dexamethasone after 72 h. These results suggest that intestinal epithelial cells may be programmed to activate a PCD pathway upon detachment from a physiologic two-dimensional monolayer configuration, and that this process of adhesion regulated programmed cell death (ARPCD) can be substantially suppressed by expression of a mutant ras oncogene.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Reversible model of spheroid formation allows for high efficiency of gene delivery ex vivo and accurate gene assessment in vivo.

The native three-dimensional architecture of carcinomas, which governs numerous autocrine-paracrine interactions related to tumor progression, cannot be faithfully recreated in most in vitro models. Even when the three-dimensional architecture is recreated in artificial scaffolds such as soft agar, this approach does not truly recreate the natural microenvironment of the tumor. Multicellular spheroids can reasonably recreate in vitro the natural three-dimensional architecture of carcinomas, but even the most efficient gene delivery vectors will penetrate only the outer layers of these structures and hence only a small fraction of cells will receive the gene of interest. If the multicellular spheroids are disrupted into a single-cell suspension in order to achieve high transfection efficiency, the single-cell production may have so altered the gene expression profile of the spheroid as to bring into question its present relevancy to in vivo tumor progression. Our laboratory has developed a human-SCID (severe combined immunodeficient) mouse model of inflammatory breast cancer, MARY-X, which grows as tight multicellular spheroids in vitro and as lymphovascular emboli in vivo. The spheroids, which express only low levels of surface sialyl-Lewis(x/a) (sLe(x/a)), are able to form compact homotypic cell clumps mediated by an intact, overexpressed E-cadherin/alpha,beta-catenin axis. The spheroids can be fully disrupted by trypsin proteolysis, anti-E-cadherin antibodies, or Ca(2+) depletion. Of these approaches the disruption with depleted Ca(2+), complete after 30 min, is fully reversible by the readdition of Ca(2+) within 6 hr. This time interval allows for a transfection "window" in which successful gene delivery can be achieved before spheroid reformation. Retroviruses (10(6)-10(7) CFU/ml) carrying the gene encoding either green fluorescent protein (GFP), a dominant-negative E-cadherin mutant (H-2K(d)-E-cad), its control (H-2K(d)-E-cad Delta C25), or alpha-1,3-fucosyltransferase III (FucT-III), an enzyme that increases surface sLe(x/a), were used to transfect either intact (wild-type) or disadhered/readhered (reformed) spheroids. There were marked differences in transfection efficiency in the reformed versus wild-type spheroids. Retroviral transfection of GFP resulted in successful delivery of this reporter gene to only the outer layer of cells of the wild-type spheroids, but to all layers of the reformed spheroids. A single retroviral transfection of H-2K(d)-E-cad, H-2K(d)-E-cad Delta C25, or FucT-III produced evidence of their respective gene expression at 72 hr throughout all layers of the reformed spheroids, but only H-2K(d)-E-cad and FucT-III produced progressive disadherence. Both H-2K(d)-E-cad-MARY-X and FucT-III-MARY-X lost their ability to form lymphovascular emboli in SCID mice. This reversible model of spheroid formation has provided us with insight into the pathogenesis of inflammatory breast carcinoma. If more broadly applied, this model could be used to examine the effects of any gene, using any gene delivery system in the three-dimensional context of native tumoral architecture.

Animals↗
PubMed1997

StuAp is a sequence-specific transcription factor that regulates developmental complexity in Aspergillus nidulans.

The Aspergillus nidulans Stunted protein (StuAp) regulates multicellular complexity during asexual reproduction by moderating the core developmental program that directs differentiation of uninucleate, terminally differentiated spores from multinucleate, vegetative hyphae. StuAp is also required for ascosporogenesis and multicellular development during sexual reproduction. StuAp is a member of a family of fungal transcription factors that regulate development or cell cycle progression. Further, StuAp characterizes a sub-family possessing the conserved APSES domain. We demonstrate for the first time that the APSES domain is a sequence-specific DNA-binding domain that can be modeled as a basic helix-loop-helix (bHLH)-like structure. We have found that StuAp response elements (A/TCGCGT/ANA/C) are located upstream of both critical developmental regulatory genes and cell cycle genes in A.nidulans. StuAp is shown to act as a transcriptional repressor in A.nidulans, but as a weak activator in budding yeast. Our data suggest that the differentiation of pseudohyphal-like sterigmatal cells during multicellular conidiophore development requires correct StuAp-regulated expression of both developmental and cell cycle genes in A.nidulans. The budding pattern of sterigmata may involve processes related to those controlling pseudohyphal growth in budding yeast.

Amino Acid Sequence↗
PubMed1997

Selective transfer of cryopreserved human embryos with further cleavage after thawing increases delivery and implantation rates.

We investigated whether further in-vitro culture of human multicellular embryos that survive cryopreservation can select the viable embryos for transfer. Embryos for cryopreservation were supernumerary multicellular embryos obtained after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatments, with <20% of their volume filled with anucleate fragments. These had been cryopreserved using a slow-freezing and slow-thawing protocol with 1.5 M dimethylsulphoxide as the cryoprotectant. From the start of our cryopreservation programme until September 12, 1994, the thawing strategy was to thaw frozen embryos up to the exact number needed for transfer. Embryos for transfer were selected on the basis of their morphological appearance and embryo transfer to the patient was done on the day of thawing. From September 12, 1994 onwards we used a more selective thawing strategy where a cohort of up to a maximum of 12 frozen embryos per patient is thawed from which embryos of the best morphological quality, and which are furthest advanced in terms of cleavage after a 24 h in-vitro culture period in Menezo B2 medium, are selected. We took delivery rates, embryo implantation rates and birth rates into account to see if there is any difference between the following three types of transfers used: 187 transfers exclusively of embryos having continued to cleave after thawing, 107 mixed transfers of embryos with and without further cleavage and 53 transfers exclusively of embryos with no further cleavage. The overall outcome in terms of delivery rate and embryo implantation and birth rates were not different between the new and the earlier thawing policies (6.6, 5.2 and 3.6% versus 6.0, 4.1 and 2.7% respectively). Only when a distinction was made between transfers on the basis of the presence of embryos with further cleavage, did the advantage of selection on the basis of cleavage capacity become evident. Significantly higher delivery and embryo implantation and birth rates (11.2, 7.7 and 6.5% respectively) were recorded with transfers exclusively of embryos with further cleavage versus mixed transfers of embryos with and without further cleavage (1.9, 2.9 and 0.6% respectively). Fifty-three transfers exclusively of embryos with no further cleavage did not lead to any delivery. Our results demonstrate that selection of human multicellular embryos which survive cryopreservation and continue to cleave in vitro can significantly improve the delivery rate per transfer and the implantation rate per transferred embryo.

Abortion, Spontaneous↗
PubMed2005

mRNA-mediated intron losses: evidence from extraordinarily large exons.

Multicellular eukaryotes that have high intron density have their introns almost evenly distributed within genes, but unicellular eukaryotes that are generally intron poor have their introns asymmetrically distributed toward the 5' ends of genes. This was explained by homologous recombination of genomic DNA with the cDNA reverse transcribed from the 3' polyadenylated tail of spliced mRNA. This paper is to study whether mRNA-mediated intron losses have ever occurred in multicellular eukaryotes. If intron losses were mRNA-mediated, adjacent introns should be commonly lost together. A direct result is fusion of several previously adjacent exons and producing a large exon. We found that extraordinarily large exons (ELEs) are common not only in unicellular eukaryotes but also in multicellular eukaryotes. The percentage of genes having ELEs is negatively correlated with intron abundance. In addition, the number of lost introns estimated from the relative lengths of ELEs is negatively correlated with the number of extant introns. These results support mRNA-mediated intron losses in all eukaryotes. Moreover, we found that the ELEs of intron-common eukaryotes (with more than 0.5 intron per gene on average) are not only located at 3' ends but also at 5' ends and the middle of genes. This is contrary to what would be expected if the involved cDNAs were reverse transcribed from the 3' polyadenosine ends. A remarkable difference in intron distribution was revealed between intron-rare eukaryotes and intron-common eukaryotes. The intron-rare eukaryotes show very strong 5'-biased intron distribution, whereas the intron-common eukaryotes display even intron distribution or only weak 5'-biased distribution. We suspected that intron losses from 3' end of genes may be limited in intron-rare eukaryotes. The intron losses from intron-common eukaryotes should have other priming mechanism, like self-primed reverse transcription.

Animals↗
PubMed2004

Analyses of cDNAs from growth and slug stages of Dictyostelium discoideum.

Dictyostelium is a favored model for studying problems in cell and developmental biology. To comprehend the genetic potential and networks that direct growth and multicellular development, we are performing a large-scale analysis of Dictyostelium cDNAs. Here, we newly determine 7720 nucleotide sequences of cDNAs from the multicellular, slug stage (S) and 10 439 from the unicellular, vegetative stage (V). The combined 26 954 redundant ESTs were computer assembled using the PHRAP program to yield 5381 independent sequences. These 5381 predicted genes represent about half of the estimated coding potential of the organism. One-third of them were classified into 12 functional categories. Although the overall classification patterns of the V and S libraries were very similar, stage-specific genes exist in every category. The majority of V-specific genes function in some aspect of protein translation, while such genes are in a minority in the S-specific and common populations. Instead, genes for signal transduction and multicellular organization are enriched in the population of S-specific genes. Genes encoding the enzymes of basic metabolism are mainly found in the common gene population. These results therefore suggest major differences between growing and developing Dictyostelium cells in the nature of the genes transcribed.

Animals↗
PubMed1992

Molecular phylogeny of the volvocine flagellates.

Phylogenetic studies of approximately 2,000 bases of sequence from the large and small nuclear-encoded ribosomal RNAs are used to investigate the origins of the genus Volvox. The colonial and multicellular genera currently placed in the family Volvocaceae form a monophyletic group that is significantly closer phylogenetically to Chlamydomonas reinhardtii than it is to the other unicellular green flagellates that were tested, including Chlamydomonas eugametos, Chlorella pyrenoidosa, and Haematococcus lacustris. Statistical analysis of 251 phylogenetically informative nucleotide positions rejects the "volvocine lineage" hypothesis, which postulates a monophyletic evolutionary progression from unicellular organisms (such as Chlamydomonas), through colonial organisms (e.g., Gonium, Pandorina, Eudorina, and Pleodorina) demonstrating increasing size, cell number, and tendency toward cellular differentiation, to multicellular organisms having fully differentiated somatic and reproductive cells (in the genus Volvox). The genus Volvox appears not to be monophyletic. Volvox capensis falls outside a lineage containing other representatives of Volvox (V. aureus, V. carteri, and V. obversus), and both of these Volvox lineages are more closely related to certain colonial genera than they are to each other. This implies either a diphyletic origin of Volvox from different colonial volvocacean ancestors, a phylogenetic derivation of some of the colonial genera from a multicellular (i.e., Volvox) ancestor, or both. Considered together with previously published observations, these results suggest that the different levels of organizational and developmental complexity found in the Volvocaceae represent alternative stable states, among which evolutionary transitions have occurred several times during the phylogenetic history of this group.

Animals↗
PubMed2000

The origin of alternation of generations in land plants: a focus on matrotrophy and hexose transport.

A life history involving alternation of two developmentally associated, multicellular generations (sporophyte and gametophyte) is an autapomorphy of embryophytes (bryophytesphytes + vascular plants). Microfossil data indicate that Mid Late Ordovician land plants possessed such a life cycle, and that the origin of alternation of generations preceded this date. Molecular phylogenetic data unambiguously relate charophycean green algae to the ancestry of monophyletic embryophytes, and identify bryophytes as early-divergent land plants. Comparison of reproduction in charophyceans and bryophytes suggests that the following stages occurred during evolutionary origin of embryophytic alternation of generations: (i) origin of oogamy; (ii) retention of eggs and zygotes on the parental thallus; (iii) origin of matrotrophy (regulated transfer of nutritional and morphogenetic solutes from parental cells to the next generation); (iv) origin of a multicellular sporophyte generation; and (v) origin of non-flagellate, walled spores. Oogamy, egg/zygote retention and matrotrophy characterize at least some modern charophvceans, and are postulated to represent pre-adaptative features inherited by embryophytes from ancestral charophyceans. Matrotrophy is hypothesized to have preceded origin of the multicellular sporophytes of' plants, and to represent a critical innovation. Molecular approaches to the study of the origins of matrotrophy include assessment of hexose transporter genes and protein family members and their expression patterns. The occurrence in modern charophyceans and bryophytes of chemically resistant tissues that exhibit distinctive morphology correlated with matrotrophy suggests that Early-Mid Ordovician or older microfossils relevant to the origin of land plant alternation of generations may be found.

Animals↗
PubMed2000

Relatedness and the fraternal major transitions.

Many of the major transitions in evolution involved the coalescence of independent lower-level units into a higher organismal level. This paper examines the role of kinship, focusing on the transitions to multicellularity in animals and to coloniality in insects. In both, kin selection based on high relatedness permitted cooperation and a reproductive division of labour. The higher relatedness of haplodiploid females to their sisters than to their offspring might not have been crucial in the origin of insect societies, and the transition to multicellularity shows that such special relationships are not required. When multicellular forms develop from a single cell, selfish conflict is minimal because each selfish mutant obtains only one generation of within-individual advantage in a chimaera. Conditionally expressed traits are particularly immune to within-individual selfishness because such mutations are rarely expressed in chimaeras. Such conditionally expressed altruism genes lead easily to the evolution of the soma, and the germ line might simply be what is left over. In most social insects, differences in relatedness ensure that there will be potential conflicts. Power asymmetries sometimes lead to such decisive settlements of conflicts that social insect colonies can be considered to be fully organismal.

Animals↗
PubMed2006

Sexual conflict and the alternation of haploid and diploid generations.

Land plants possess a multicellular diploid stage (sporophyte) that begins development while attached to a multicellular haploid progenitor (gametophyte). Although the closest algal relatives of land plants lack a multicellular sporophyte, they do produce a zygote that grows while attached to the maternal gametophyte. The diploid offspring shares one haploid set of genes with the haploid mother that supplies it with resources and a paternal haploid complement that is not shared with the mother. Sexual conflict can arise within the diploid offspring because the offspring's maternal genome will be transmitted in its entirety to all other sexual and asexual offspring that the mother may produce, but the offspring's paternally derived genes may be absent from these other offspring. Thus, the selective forces favouring the evolution of genomic imprinting may have been present from the origin of modern land plants. In bryophytes, where gametophytes are long-lived and capable of multiple bouts of asexual and sexual reproduction, we predict strong sexual conflict over allocation to sporophytes. Female gametophytes of pteridophytes produce a single sporophyte and often lack means of asexual reproduction. Therefore, sexual conflict is predicted to be attenuated. Finally, we explore similarities among models of mate choice, offspring choice and segregation distortion.

Bryophyta↗
PubMed1996

The Dictyostelium MAP kinase ERK2 regulates multiple, independent developmental pathways.

We showed previously that the MAP kinase ERK2 is essential for aggregation. erk2 null cells lack cAMP stimulation of adenylyl cyclase and thus cannot relay the cAMP chemotactic signal, although the cells chemotax to cAMP (Segall et al. 1995). In this paper we have examined the role of ERK2 in controlling developmental gene expression and morphogenesis during the multicellular stages, making use of a temperature-sensitive ERK2 mutation. Using suspension assays, we show that ERK2 is not essential for aggregation-stage, cAMP pulse-induced gene expression, or for the expression of postaggregative genes, which are induced at the onset of mound formation in response to cAMP in wild-type cells. In contrast, the prespore-specific gene SP60 is not induced and the prestalk-specific gene ecmA is induced but at a significantly reduced level. Chimeric organisms, comprised of wild-type and erk2 null cells expressing the prestalk-specific ecmA/lacZ reporter, show an abnormal spatial patterning, in which Erk2ts/erk2 cells are excluded from the very anterior prestalk A region. To further examine the function of ERK2 during the multicellular stages, we bypassed the requirement of ERK2 for aggregation by creating an ERK2 temperature-sensitive mutant. erk2 null cells expressing the ERK2ts mutant develop normally at 20 degrees C and express cell-type-specific genes but do not aggregate at temperatures above 25 degrees C. Using temperature shift experiments, we showed that ERK2 is essential for proper morphogenesis and for the induction and maintenance of prespore but not prestalk gene expression. Our results indicate that ERK2 functions at independent stages during Dictyostelium development to control distinct developmental programs: during aggregation, ERK2 is required for the activation of adenylyl cyclase and during multicellular development, ERK2 is essential for morphogenesis and cell-type-specific gene expression. Analysis of these results and other supports the conclusion that the requirement of ERK2 for cell-type differentiation is independent of its role in the activation of adenylyl cyclase.

Amino Acid Sequence↗
PubMed2000

Assessment of compositional heterogeneity within and between eukaryotic genomes.

Using large amounts of long genomic sequences, we studied the compositional patterns of eukaryotic genomes. We developed a simple measure, the compositional heterogeneity (or variability) index, to compare the differences in compositional heterogeneity between long genomic sequences. The index measures the average difference in GC content between two adjacent windows normalized by the standard error expected under the assumption of random distribution of nucleotides in a window. We report the following findings: (1) The extent of the compositional heterogeneity in a genomic sequence strongly correlates with its GC content in all multicellular eukaryotes studied regardless of genome size. (2) The human genome appears to be highly compositionally heterogeneous both within and between individual chromosomes; the heterogeneity goes much beyond the predictions of the isochore model. (3) All genomes of multicellular eukaryotes examined in this study are compositionally heterogeneous, although they also contain compositionally uniform segments, or isochores. (4) The true uniqueness of the human (or mammalian) genome is the presence of very high GC regions, which exhibit unusually high compositional heterogeneity and contain few long homogeneous segments (isochores). In general, GC-poor isochores tend to be longer than GC-rich ones. These findings indicate that the genomes of multicellular organisms are much more heterogeneous in nucleotide composition than depicted by the isochore model and so lead to a looser definition of isochores.

Algorithms↗