Genetic addiction: selfish gene's strategy for symbiosis in the genome

The evolution and maintenance of the phenomenon of postsegregational host killing or genetic addiction are paradoxical. In this phenomenon, a gene complex, once established in a genome, programs death of a host cell that has eliminated it. The intact form of the gene complex would survive in other members of the host population. It is controversial as to why these genetic elements are maintained, due to the lethal effects of host killing, or perhaps some other properties are beneficial to the host. We analyzed their population dynamics by analytical methods and computer simulations. Genetic addiction turned out to be advantageous to the gene complex in the presence of a competitor genetic element. The advantage is, however, limited in a population without spatial structure, such as that in a well-mixed liquid culture. In contrast, in a structured habitat, such as the surface of a solid medium, the addiction gene complex can increase in frequency, irrespective of its initial density. Our demonstration that genomes can evolve through acquisition of addiction genes has implications for the general question of how a genome can evolve as a community of potentially selfish genes.     

The evolution of resistance against good and bad infections

Opportunities for genetic exchange are abundant between bacteria and foreign genetic elements (FGEs) such as conjugative plasmids, transposable elements and bacteriophages. The genetic novelty that may arise from these forms of genetic exchange is potentially beneficial to bacterial hosts, but there are also potential costs, which may be considerable in the case of phage infection. Some bacterial resistance mechanisms target both beneficial and deleterious forms of genetic exchange. Using a general epidemiological model, we explored under which conditions such resistance mechanisms may evolve. We considered a population of hosts that may be infected by FGEs that either confer a benefit or are deleterious to host fitness, and we analysed the epidemiological and evolutionary outcomes of resistance evolving under different cost/benefit scenarios. We show that the degree of co‐infection between these two types of infection is particularly important in determining the evolutionarily stable level of host resistance. We explore these results using the example of CRISPR‐Cas, a form of bacterial immunity that targets a variety of FGEs, and we show the potential role of bacteriophage infection in selecting for resistance mechanisms that in turn limit the acquisition of plasmid‐borne antibiotic resistance. Finally, beyond microbes, we discuss how endosymbiotic associations may have shaped the evolution of host immune responses to pathogens.     

Patterns of piRNA Regulation in Drosophila Revealed through Transposable Element Clade Inference

Transposable elements (TEs) are self-replicating “genetic parasites” ubiquitous to eukaryotic genomes. In addition to conflict between TEs and their host genomes, TEs of the same family are in competition with each other. They compete for the same genomic niches while experiencing the same regime of copy-number selection. This suggests that competition among TEs may favor the emergence of new variants that can outcompete their ancestral forms. To investigate the sequence evolution of TEs, we developed a method to infer clades: collections of TEs that share SNP variants and represent distinct TE family lineages. We applied this method to a panel of 85 Drosophila melanogaster genomes and found that the genetic variation of several TE families shows significant population structure that arises from the population-specific expansions of single clades. We used population genetic theory to classify these clades into younger versus older clades and found that younger clades are associated with a greater abundance of sense and antisense piRNAs per copy than older ones. Further, we find that the abundance of younger, but not older clades, is positively correlated with antisense piRNA production, suggesting a general pattern where hosts preferentially produce antisense piRNAs from recently active TE variants. Together these findings suggest a pattern whereby new TE variants arise by mutation and then increase in copy number, followed by the host producing antisense piRNAs that may be used to silence these emerging variants.     

General principles of single-construct chromosomal gene drive

Gene drive systems are genetic elements capable of spreading into a population even if they confer a fitness cost to their host. We consider a class of drive systems consisting of a chromosomally located, linked cluster of genes, the presence of which renders specific classes of offspring arising from specific parental crosses unviable. Under permissive conditions, a number of these elements are capable of distorting the offspring ratio in their favor. We use a population genetic framework to derive conditions under which these elements spread to fixation in a population or induce a population crash. Many of these systems can be engineered using combinations of toxin and antidote genes, analogous to Medea, which consists of a maternal toxin and zygotic antidote. The majority of toxin-antidote drive systems require a critical frequency to be exceeded before they spread into a population. Of particular interest, a Z-linked Medea construct with a recessive antidote is expected to induce an all-male population crash for release frequencies above 50%. We suggest molecular tools that may be used to build these systems, and discuss their relevance to the control of a variety of insect pest species, including mosquito vectors of diseases such as malaria and dengue fever.     

Cytoplasmic feminizing elements in a two-population model: infection dynamics, gene flow modification, and the spread of autosomal suppressors

We investigate the dynamics of a cytoplasmic parasitic element with feminizing effect in a two-population model. We assume that the host species has a ZZ/ZW sex determination system. Our analysis reveals that the feminizer and the W chromosome can stably coexist by dominating different populations if the transmission rate differs significantly between the populations and migration is sufficiently weak. In the equilibrium of coexistence, genetic influx at any host autosomal locus is strongly enhanced in the population where infection is prevalent but not modified in the other population. We further explore conditions for the spread of autosomal suppressor genes that reduce transmission of feminizing elements to the cost of host viability, and compute their equilibrium frequencies. Our results confirm the hypothesis that selfish genetic elements convert infected host populations into genetic sinks, thereby restricting the spread of transmission suppressors.     

Fungal transposable elements: Generators of diversity and genetic tools

Representatives of several classes of transposable elements (TEs) have been characterized in a broad range of fungal species. The studies indicate that these elements are ancient and ubiquitous components of fungal genomes. Some of these elements have been shown to actively affect gene structure and function in several ways: inactivation of gene expression upon insertion, modification of the nucleotide sequence through excision, and probably by inducing extensive chromosomal rearrangements. The ability of TEs to generate a high degree of genetic diversity may therefore be important in the evolution of the fungal genome. TEs also have many potential applications in genetic research, including insertional mutagenesis and population fingerprinting, as well as gene transfer within and between species. All these genetic approaches are important as tools in studies of molecular biology and evolution of fungal species, many of which lack a functional sexual cycle.     

Effects of emerging infectious diseases on host population genetics: a review

Emerging infectious diseases threaten the survival of many species and populations by causing large declines and altering life history traits and population demographics. Therefore, it is imperative to understand how diseases impact wildlife populations so that effective management strategies can be planned. Many studies have focused on understanding the ecology of host/pathogen interactions, but it is equally important to understand the effects on host population genetic structure. In this review, we examined the literature on how infectious diseases influence host population genetic makeup, with a particular focus on whether or not they alter gene flow patterns, reduce genetic variability, and drive selection. Although the results were mixed, there was evidence for all of these outcomes. Diseases often fragmented populations into small, genetically distinct units with limited gene flow among them. In some cases, these isolated populations showed the genetic hallmarks of bottlenecks and inbreeding, but in other populations, there was sufficient gene flow or enough survivors to prevent genetic drift and inbreeding. Direct evidence of diseases acting as selective pressures in wild populations is somewhat limited, but there are several clear examples of it occurring. Also, several studies found that gene flow can impact the evolution of small populations either beneficially, by providing them with variation, or detrimentally, by swamping them with alleles that are not locally adaptive. Thus, differences in gene flow levels may explain why some species adapt while others do not. There are also intermediate cases, whereby some species may adapt to disease, but not at a rate that is meaningful for conservation purposes.     

Invasion of a multitude of genetic niches by mobile endonuclease genes

Persistence of a mobile DNA element in a population reflects a balance between the ability of the host to eliminate the element and the ability of the element to survive and to disseminate to other individuals. In each of the three biological kingdoms, several families of a mobile DNA element have been identified which encode a single protein that acts on nucleic acids. Collectively termed homing endonuclease genes (HEGs), these elements employ varied strategies to ensure their survival. Some members of the HEG families have a minimal impact on host fitness because they associate with genes having self-splicing introns or inteins that remove the HEGs at the RNA or protein level. The HEG and the intron/intein gene spread throughout the population by a gene conversion process initiated by the HEG-encoded endonuclease called 'homing' in which the HEG and intron/intein genes are copied to cognate alleles that lack them. The endonuclease activity also contributes to a high frequency of lateral transmission of HEGs between species as has been documented in plants and other systems. Other HEGs have positive selection value because the proteins have evolved activities that benefit their host organisms. The success of HEGs in colonizing diverse genetic niches results from the flexibility of the encoded endonucleases in adopting new specificities.     

Site-specific selfish genes as tools for the control and genetic engineering of natural populations

Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sex-linked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.     

Surprisingly little population genetic structure in a fungus‐associated beetle despite its exploitation of multiple hosts

In heterogeneous environments, landscape features directly affect the structure of genetic variation among populations by functioning as barriers to gene flow. Resource‐associated population genetic structure, in which populations that use different resources (e.g., host plants) are genetically distinct, is a well‐studied example of how environmental heterogeneity structures populations. However, the pattern that emerges in a given landscape should depend on its particular combination of resources. If resources constitute barriers to gene flow, population differentiation should be lowest in homogeneous landscapes, and highest where resources exist in equal proportions. In this study, we tested whether host community diversity affects population genetic structure in a beetle (Bolitotherus cornutus) that exploits three sympatric host fungi. We collected B. cornutus from plots containing the three host fungi in different proportions and quantified population genetic structure in each plot using a panel of microsatellite loci. We found no relationship between host community diversity and population differentiation in this species; however, we also found no evidence of resource‐associated differentiation, suggesting that host fungi are not substantial barriers to gene flow. Moreover, we detected no genetic differentiation among B. cornutus populations separated by several kilometers, even though a previous study demonstrated moderate genetic structure on the scale of a few hundred meters. Although we found no effect of community diversity on population genetic structure in this study, the role of host communities in the structuring of genetic variation in heterogeneous landscapes should be further explored in a species that exhibits resource‐associated population genetic structure.     

Correlates of Viral Richness in Bats (Order Chiroptera)

Historic and contemporary host ecology and evolutionary dynamics have profound impacts on viral diversity, virulence, and associated disease emergence. Bats have been recognized as reservoirs for several emerging viral pathogens, and are unique among mammals in their vagility, potential for long-distance dispersal, and often very large, colonial populations. We investigate the relative influences of host ecology and population genetic structure for predictions of viral richness in relevant reservoir species. We test the hypothesis that host geographic range area, distribution, population genetic structure, migratory behavior, International Union for Conservation of Nature and Natural Resources (IUCN) threat status, body mass, and colony size, are associated with known viral richness in bats. We analyze host traits and viral richness in a generalized linear regression model framework, and include a correction for sampling effort and phylogeny. We find evidence that sampling effort, IUCN status, and population genetic structure correlate with observed viral species richness in bats, and that these associations are independent of phylogeny. This study is an important first step in understanding the mechanisms that promote viral richness in reservoir species, and may aid in predicting the emergence of viral zoonoses from bats.     

Transgenic animal studies on the evolution of genetic regulatory circuitries.

The ability to transfer genes from one species to another provides a powerful method to study genetic regulatory differences between species in a homogeneous genetic background. A survey of several transgenic animal experiments indicates that the vast majority of regulatory differences observed between species are due to differences in the cis-acting elements associated with the genes under study. A corollary is that in almost all cases the host species provides the necessary regulatory proteins for expression of the transgenes in specific tissues in which the endogenous homolog is not expressed. Although the details of the cis-acting differences are unknown for most cases, it appears that these differences may consist of the acquisition or loss of unique elements or subtle variation of conserved elements. It is unknown whether much of this variation is directly related to adaptive evolution. The identification of the promoter/enhancer elements responsible for these differences is an important first step in examining the functional significance of this variation.     

DNA methylation of mobile genetic elements in human cancers

Mobile genetic elements are responsible for half of the human genome, creating the host genomic instability or variability through several mechanisms. Two types of abnormal DNA methylation in the genome, hypomethylation and hypermethylation, are associated with cancer progression. Genomic hypermethylation has been most often observed on the CpG islands around gene promoter regions in cancer cells. In contrast, hypomethylation has been observed on mobile genetic elements in the cancer cells. It is recently considered that the hypomethylation of mobile genetic elements may play a biological role in cancer cells along with the DNA hypermethylation on CpG islands. Growing evidence has indicated that mobile genetic elements could be associated with the cancer initiation and progression through the hypomethylation. Here we review the recent progress on the relationship between DNA methylation and mobile genetic elements, focusing on the hypomethylation of LINE-1 and HERV elements in various human cancers and suggest that DNA hypomethylation of mobile genetic elements could have potential to be a new cancer therapy target in the future.     

Isolation and characterization of functional insertion sequences of rhizobia

Rhizobia are a group of bacteria that form nodules on the roots of legume host plants. The sequenced genomes of the rhizobia are characterized by the presence of many putative insertion sequences (IS) elements. However, it is unknown whether these IS elements are functional and it is therefore relevant to assess their transposition activity. In this work, several functional insertion sequences belonging to the IS1256, IS3, IS5, IS166, and IS21 families were captured from Rhizobium tropici, Rhizobium sp. NGR234 and Sinorhizobium meliloti, using pGBG1 as a trapping system. In silico analysis shows that homologs of rhizobia mobile elements are present in distantly related genomes, suggesting that Rhizobium IS elements are prone to genetic transfer.     

Segregational Drift Constrains the Evolutionary Rate of Prokaryotic Plasmids

Plasmids are extrachromosomal genetic elements in prokaryotes that have been recognized as important drivers of microbial ecology and evolution. Plasmids are found in multiple copies inside their host cell where independent emergence of mutations may lead to intracellular genetic heterogeneity. The intracellular plasmid diversity is thus subject to changes upon cell division. However, the effect of plasmid segregation on plasmid evolution remains understudied. Here, we show that genetic drift during cell division—segregational drift—leads to the rapid extinction of novel plasmid alleles. We established a novel experimental approach to control plasmid allele frequency at the levels of a single cell and the whole population. Following the dynamics of plasmid alleles in an evolution experiment, we find that the mode of plasmid inheritance—random or clustered—is an important determinant of plasmid allele dynamics. Phylogenetic reconstruction of our model plasmid in clinical isolates furthermore reveals a slow evolutionary rate of plasmid-encoded genes in comparison to chromosomal genes. Our study provides empirical evidence that genetic drift in plasmid evolution occurs at multiple levels: the host cell and the population of hosts. Segregational drift has implications for the evolutionary rate heterogeneity of extrachromosomal genetic elements.     

Hierarchical spatial structure of genetically variable nucleopolyhedroviruses infecting cyclic populations of western tent caterpillars

The cyclic population dynamics of western tent caterpillars, Malacosoma californicum pluviale, are associated with epizootics of a nucleopolyhedrovirus, McplNPV. Given the dynamic fluctuations in host abundance and levels of viral infection, host resistance and virus virulence might be expected to change during different phases of the cycle. As a first step in determining if McplNPV virulence and population structure change with host density, we used restriction fragment length polymorphism (RFLP) analysis to examine the genetic diversity of McplNPV infecting western tent caterpillar populations at different spatial scales. Thirteen dominant genetic variants were identified in 39 virus isolates (individual larvae) collected from field populations during one year of low host density, and another distinct variant was discovered among nine additional isolates in two subsequent years of declining host density. The distribution of these genetic variants was not random and indicated that the McplNPV population was structured at several spatial levels. A high proportion of the variation could be explained by family grouping, which suggested that isolates collected within a family were more likely to be the same than isolates compared among populations. Additionally, virus variants from within populations (sites) were more likely to be the same than isolates collected from tent caterpillar populations on different islands. This may indicate that there is limited mixing of virus among tent caterpillar families and populations when host population density is low. Thus there is potential for the virus to become locally adapted to western tent caterpillar populations in different sites. However, no dominant genotype was observed at any site. Whether and how selection acts on the genetically diverse nucleopolyhedrovirus populations as host density changes will be investigated over the next cycle of tent caterpillar populations.     

Site-specific retrotransposons of the trypanosomatid protozoa

Retrotransposons are mobile genetic elements that have invaded a wide variety of organisms. While these mobile elements share gene homologies and structural features with retroviruses, they have lost the ability to produce infectious particles. Typically these elements are 5-10 kilobases (kb) in length, are conserved in their structural organization and are present in many copies in the genomes into which they have integrated(1). Retrotransposons generally interrupt their host genome promiscuously and thus cause a variety of random effects. In general, their insertion results in mutations, inversions, deletions or rearrangements among host sequences. All of these changes are thought to add to the plasticity of the host genome and thus contribute to a faster pace of evolutionary development. However, because of the random nature of insertions, it has been difficult to attribute any one specific function to these diverse elements. Here, Serap Aksoy describes a newly recognized family of mobile elements that are different from most retrotransposons in that they have the ability to integrate into specific host sequences.     

Common themes in microbial pathogenicity revisited.

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics.     

Models of the population genetics of transposable elements

Although transposable elements (TEs) have been found in all organisms in which they have been looked for, the ways in which they invade genomes and populations are still a matter of debate. By extending the classical models of population genetics, several approaches have been developed to account for the dynamics of TEs, especially in Drosophila melanogaster . While the formalism of these models is based on simplifications, they enable us to understand better how TEs invade genomes, as a result of multiple evolutionary forces including duplication, deletion, self-regulation, natural selection and genetic drift. The aim of this paper is to review the assumptions and the predictions of these different models by highlighting the importance of the specific characteristics of both the TEs and the hosts, and the host/TE relationships. Then, perspectives in this domain will be discussed.     

A retrotransposon-like element and its occurrence in British Columbia populations of Chondrostereum purpureum

Repetitive DNA elements discovered in the basidiomycete Chondrostereum purpureum were characterized and validated for use as genetic markers. Regions of these marker sequences were similar to retrotransposon and retrotransposon-like sequences, as indicated by BLAST searches of NCBI databases. These sequences occur in multiple DNA fragments of variable length in a given C. purpureum isolate, and thus can serve as strain-specific genetic markers. The segregation of the markers within a progeny set demonstrated their stability through meiosis. The population structure of C. purpureum was assessed using the markers. There was no evidence of a barrier to gene flow between C. purpureum populations separated by 1400 km and no indication of population sub-structuring based on host or geographical source of isolate. Repetitive fragments were amplified from four other species, suggesting the occurrence of these retrotransposon-like elements in other basidiomycetes and the potential utility of these markers for other fungi.