Promiscuous mitochondria in Cryptococcus gattii

Cryptococcus gattii is a primary pathogenic basidiomycetous yeast comprising four genotypic groups. Here we present data on two mitochondrial loci (MtLrRNA and ATP6 ). Two of the genotypic groups, namely amplified fragment length polymorphism (AFLP)5/VGIII and AFLP6/VGII, formed monophyletic lineages. The AFLP4/VGI genotypic group, however, possessed five different mitochondrial genotypes that did not form a monophyletic lineage. The majority of these isolates contained mitochondrial genomes that are partially identical to those found in isolates belonging to AFLP6/VGII, which is causing the ongoing and expanding Vancouver Island outbreak. Two out of four AFLP7/VGIV isolates contained an AFLP4/VGI allele of MtLrRNA. These observations are best explained by assuming a process of mitochondrial recombination. If this is true, mitochondrial recombination seems possible between cells belonging to different genotypic groups of C. gattii , especially between AFLP6/VGII or AFLP7/VGIV and AFLP4/VGI. We also have to assume that mitochondria, most likely, were transferred from cells belonging to AFLP6/VGII to AFLP4/VGI. As such a process of mitochondrial recombination is only possible after cell–cell conjugation, this may also allow the further exchange of genetic material, for example nuclear or plasmid in nature, between different genotypes of C. gattii . This may be relevant as it may provide a possible mechanism contributing to the modulation of virulence attributes of isolates, such as has been observed in the ongoing Vancouver Island outbreak of C. gattii .     

Promiscuous females protect their offspring

Multi-male mating (MMM) by females is relatively common among mammals, occurring in at least 133 species and several evolutionary benefits of MMM have been proposed. The most convincing explanation is that MMM confuses paternity, thereby deterring infanticide by males. A second explanation for females that are unlikely to experience infanticide is that MMM is a consequence of sexual harassment. Mate guarding and, perhaps even in some cases, behavioral monogamy, might have evolved in response to the threat of infanticide and the subsequent tendency for females to mate multiply. Benefits relating to improved genetic fitness of offspring do occur in some species, but do not provide a widespread explanation for the evolutionary origin of MMM; if cryptic female choice through sperm competition is adaptive to females it probably evolved as a consequence of, rather than a precursor to, female promiscuity. Here, we provide support for the original hypothesis of paternity confusion for MMM, rather than for the more popular good genes or sperm competition hypotheses.     

Promiscuous interactions between AMPA-Rs and MAGUKs

What controls the number of AMPA receptors at excitatory synapses? MAGUKs are known to play a critical role in this process, but which ones are involved and when has been contentious. In this issue of Neuron, Elias et al. have elucidated the roles of three MAGUKs, PSD-95, PSD-93, and SAP-102, in the targeting of AMPA receptors to synapses in hippocampal neurons.     

Promiscuous females avoid inbreeding by controlling sperm storage

Recent studies in a variety of species have shown that polyandrous females are somehow able to bias paternity against their relatives postcopulation, although how they do so remains unknown. Field crickets readily mate with their siblings, but when also mated to an unrelated male, they produce disproportionately fewer inbred offspring. We use a new competitive microsatellite polymerase chain reaction technique to determine the contribution of males to stored sperm and subsequent paternity of offspring. Paternity is almost completely predicted by how much sperm from a particular male is stored, and unrelated males contribute more sperm to storage and have a corresponding higher paternity success.     

Promiscuous mating produces offspring with higher lifetime fitness

In many species, each female pairs with a single male for the purpose of rearing offspring, but may also engage in extra-pair copulations. Despite the prevalence of such promiscuity, whether and how multiple mating benefits females remains an open question. Multiple mating is typically thought to be favoured primarily through indirect benefits (i.e. heritable effects on the fitness of offspring). This prediction has been repeatedly tested in a variety of species, but the evidence has been equivocal, perhaps because such studies have focused on pre-reproductive survival rather than lifetime fitness of offspring. Here, we show that in a songbird, the dark-eyed junco (Junco hyemalis), both male and female offspring produced by extra-pair fertilizations have higher lifetime reproductive success than do offspring sired within the social pair. Furthermore, adult male offspring sired via extra-pair matings are more likely to sire extra-pair offspring (EPO) themselves, suggesting that fitness benefits to males accrue primarily through enhanced mating success. By contrast, female EPO benefited primarily through enhanced fecundity. Our results provide strong support for the hypothesis that the evolution of extra-pair mating by females is favoured by indirect benefits and shows that such benefits accrue much later in the offspring's life than previously documented.     

Promiscuous mismatch extension by human DNA polymerase lambda

DNA polymerase lambda (Pol λ) is one of several DNA polymerases suggested to participate in base excision repair (BER), in repair of broken DNA ends and in translesion synthesis. It has been proposed that the nature of the DNA intermediates partly determines which polymerase is used for a particular repair reaction. To test this hypothesis, here we examine the ability of human Pol λ to extend mismatched primer-termini, either on ‘open’ template-primer substrates, or on its preferred substrate, a 1 nt gapped-DNA molecule having a 5′-phosphate. Interestingly, Pol λ extended mismatches with an average efficiency of ≈10⁻² relative to matched base pairs. The match and mismatch extension catalytic efficiencies obtained on gapped molecules were ≈260-fold higher than on template-primer molecules. A crystal structure of Pol λ in complex with a single-nucleotide gap containing a dG·dGMP mismatch at the primer-terminus (2.40 Å) suggests that, at least for certain mispairs, Pol λ is unable to differentiate between matched and mismatched termini during the DNA binding step, thus accounting for the relatively high efficiency of mismatch extension. This property of Pol λ suggests a potential role as a ‘mismatch extender’ during non-homologous end joining (NHEJ), and possibly during translesion synthesis.     

Promiscuous genes and chromosomal rearrangements of hematopoietic malignancies

The nonrandomness of chromosomal abnormalities of hematopoietic malignancies, which has been established twenty years ago, has evidenced a more or less close relationship between some structural chromosomal abnormalities and leukemia subtypes. The same relation was, then, shown between gene and chromosome rearrangements. It becomes now obvious that genes involved in malignant proliferations may rearrange several different partner genes, as for instance the genes MLL, localised to chromosome band 11q23, and ETV6/TEL to 12p13. The study of these rearrangements is of particular importance in order to improve our knowledge of the functions of rearranged genes as well as their normal counterparts, and to analyse mechanisms favoring the occurrence of chromosomal rearrangements in malignancies.     

Promiscuous DNA in the nuclear genomes of hemiascomycetous yeasts

Transfer of fragments of mtDNA to the nuclear genome is a general phenomenon that gives rise to NUMTs (NUclear sequences of MiTochondrial origin). We present here the first comparative analysis of the NUMT content of entirely sequenced species belonging to a monophyletic group, the hemiascomycetous yeasts ( Candida glabrata, Kluyveromyces lactis, Kluyveromyces thermotolerans, Debaryomyces hansenii and Yarrowia lipolytica , along with the updated NUMT content of Saccharomyces cerevisiae ). This study revealed a huge diversity in NUMT number and organization across the six species. Debaryomyces hansenii harbors the highest number of NUMTs (145), half of which are distributed in numerous large mosaics of up to eight NUMTs arising from multiple noncontiguous mtDNA fragments inserted at the same chromosomal locus. Most NUMTs, in all species, are found within intergenic regions including seven NUMTs in pseudogenes. However, five NUMTs overlap a gene, suggesting a positive impact of NUMTs on protein evolution. Contrary to the other species, K. lactis and K. thermotolerans harbor only a few diverged NUMTs, suggesting that mitochondrial transfer to the nuclear genome has decreased or ceased in these phylogenetic branches. The dynamics of NUMT acquisition and loss are illustrated here by their species-specific distribution.     

Promiscuous and specific recognition among ephrins and Eph receptors

Eph–ephrin interactions control the signal transduction between cells and play an important role in carcinogenesis and other diseases. The interactions between Eph receptors and ephrins of the same subclass are promiscuous; there are cross-interactions between some subclasses, but not all. To understand how Eph–ephrin interactions can be both promiscuous and specific, we investigated sixteen energy landscapes of four Eph receptors (A2, A4, B2, and B4) interacting with four ephrin ligands (A1, A2, A5, and B2). We generated conformational ensembles and recognition energy landscapes starting from separated Eph and ephrin molecules and proceeding up to the formation of Eph–ephrin complexes. Analysis of the Eph–ephrin recognition trajectories and the co-evolution entropy of 400 ligand binding domains of Eph receptor and 241 ephrin ligands identified conserved residues during the recognition process. Our study correctly predicted the promiscuity and specificity of the interactions and provided insights into their recognition. The dynamic conformational changes during Eph–ephrin recognition can be described by progressive conformational selection and population shift events, with two dynamic salt bridges between EphB4 and ephrin-B2 contributing to the specific recognition. EphA3 cancer-related mutations lowered the binding energies. The specificity is not only controlled by the final stage of the interaction across the protein–protein interface, but also has large contributions from binding kinetics with the help of dynamic intermediates along the pathway from the separated Eph and ephrin to the Eph–ephrin complex.     

Promiscuous target interactions in the mariner transposon Himar1

We have previously characterized the early intermediates of mariner transposition. Here we characterize the target interactions that occur later in the reaction. We find that, in contrast to the early transposition intermediates, the strand transfer complex is extremely stable and difficult to disassemble. Transposase is tightly bound to the transposon ends constraining rotation of the DNA at the single strand gaps in the target site flanking the element on either side. We also find that although the cleavage step requires Mg2+ or Mn2+ as cofactor, the strand transfer step is also supported by Ca2+, suggesting that the structure of the active site changes between cleavage and insertion. Finally, we show that, in contrast to the bacterial cut and paste transposons, mariner target interactions are promiscuous and can take place either before or after cleavage of the flanking DNA. This is similar to the behavior of the V(D)J system, which is believed to be derived from an ancestral eukaryotic transposon. We discuss the implications of promiscuous target interactions for promoting local transposition and whether this is an adaptation to facilitate the invasion of a genome following horizontal transfer to a new host species.     

Promiscuous methylation of non-canonical DNA sites by HaeIII methyltransferase

The cytosine C5 methyltransferase M.HaeIII recognises and methylates the central cytosine of its canonical site GGCC. Here we report that M.HaeIII can also, with lower efficiency, methylate cytosines located in a wide range of non-canonical sequences. Using bisulphite sequencing we mapped the methyl- cytosine residues in DNA methylated in vitro and in vivo by M.HaeIII. Methyl-cytosine residues were observed in multiple sequence contexts, most commonly, but not exclusively, at star sites (sites differing by a single base from the canonical sequence). The most frequently used star sites had changes at positions 1 and 4, but there is little or no methylation at star sites changed at position 2. The rate of methylation of non-canonical sites can be quite significant: a DNA substrate lacking a canonical site was methylated by M.HaeIII in vitro at a rate only an order of magnitude slower than an otherwise identical substrate containing the canonical site. In vivo methylation of non-canonical sites may therefore be significant and may have provided the starting point for the evolution of restriction–modification systems with novel sequence specificities.