The dynamic relationship between polyandry and selfish genetic elements

Selfish genetic elements (SGEs) are ubiquitous in eukaryotes and bacteria, and make up a large part of the genome. They frequently target sperm to increase their transmission success, but these manipulations are often associated with reduced male fertility. Low fertility of SGE-carrying males is suggested to promote polyandry as a female strategy to bias paternity against male carriers. Support for this hypothesis is found in several taxa, where SGE-carrying males have reduced sperm competitive ability. In contrast, when SGEs give rise to reproductive incompatibilities between SGE-carrying males and females, polyandry is not necessarily favoured, irrespective of the detrimental impact on male fertility. This is due to the frequency-dependent nature of these incompatibilities, because they will decrease in the population as the frequency of SGEs increases. However, reduced fertility of SGE-carrying males can prevent the successful population invasion of SGEs. In addition, SGEs can directly influence male and female mating behaviour, mating rates and reproductive traits (e.g. female reproductive tract length and male sperm). This reveals a potent and dynamic interaction between SGEs and polyandry highlighting the potential to generate sexual selection and conflict, but also indicates that polyandry can promote harmony within the genome by undermining the spread of SGEs.     

The role of selfish genetic elements in eukaryotic evolution

'Selfish genetic elements', such as transposons, homing endonucleases, meiotic drive chromosomes and heritable microorganisms, are common features of eukaryotes. However, their importance in the evolution of eukaryotic genomes is still controversial. In this review, we discuss these diverse elements and their potential importance in the evolution of genetic systems, adaptation, and the extinction and birth of species.     

Persistence of selfish genetic elements: population structure and conflict

Selfish genetic elements are vertically transmitted factors that spread by obtaining a transmission advantage relative to the rest of the genome of their host organism, often with a cost to overall host fitness. In many cases, conventional population genetics theory predicts them spreading through populations, reaching fixation and becoming undetectable or sometimes driving the population extinct. However, in several well studied systems, these genetic elements are known to persist at relatively low, stable frequencies. Recent research suggests that several processes might explain these observations, including population structure, intragenomic conflict and coevolution.     

Fractious chromosomes: Hybrid disruption and the origin of selfish genetic elements

Supernumerary B chromosomes are dispensable elements of the genome which can be retained in populations at high frequencies, despite being deleterious, through the ability to undergo non-Mendelian inheritance. Their mode of origin is, however, obscure. Recent work on gynogenetic fish has demonstrated the incorporation of small, unstable, centromere-containing microchromosomes, probably of interspecific derivation, into an asexual lineage⁽¹⁾. That these resemble B chromosomes both in structure and behaviour is consistent with the proposal that hybridisation between closely related species may be a significant mode of origin for such selfish genetic elements. Additional work on the B chromosome of a parasitoid wasp and observations on patterns of chromosome breakage from somatic cell hybrids also support this hypothesis.     

Massive colonization of protein-coding exons by selfish genetic elements in Paramecium germline genomes

Ciliates are unicellular eukaryotes with both a germline genome and a somatic genome in the same cytoplasm. The somatic macronucleus (MAC), responsible for gene expression, is not sexually transmitted but develops from a copy of the germline micronucleus (MIC) at each sexual generation. In the MIC genome of Paramecium tetraurelia, genes are interrupted by tens of thousands of unique intervening sequences called internal eliminated sequences (IESs), which have to be precisely excised during the development of the new MAC to restore functional genes. To understand the evolutionary origin of this peculiar genomic architecture, we sequenced the MIC genomes of 9 Paramecium species (from approximately 100 Mb in Paramecium aurelia species to >1.5 Gb in Paramecium caudatum). We detected several waves of IES gains, both in ancestral and in more recent lineages. While the vast majority of IESs are single copy in present-day genomes, we identified several families of mobile IESs, including nonautonomous elements acquired via horizontal transfer, which generated tens to thousands of new copies. These observations provide the first direct evidence that transposable elements can account for the massive proliferation of IESs in Paramecium. The comparison of IESs of different evolutionary ages indicates that, over time, IESs shorten and diverge rapidly in sequence while they acquire features that allow them to be more efficiently excised. We nevertheless identified rare cases of IESs that are under strong purifying selection across the aurelia clade. The cases examined contain or overlap cellular genes that are inactivated by excision during development, suggesting conserved regulatory mechanisms. Similar to the evolution of introns in eukaryotes, the evolution of Paramecium IESs highlights the major role played by selfish genetic elements in shaping the complexity of genome architecture and gene expression.

A comparative genomics study of nine Paramecium species reveals successful invasion of genes by transposable elements in their germline genomes, showing that the internal eliminated sequences (IESs) followed an evolutionary trajectory remarkably similar to that of spliceosomal introns.     

Medea selfish genetic elements as tools for altering traits of wild populations: a theoretical analysis

One strategy for controlling transmission of insect-borne disease involves replacing the native insect population with transgenic animals unable to transmit disease. Population replacement requires a drive mechanism to ensure the rapid spread of linked transgenes, the presence of which may result in a fitness cost to carriers. Medea selfish genetic elements have the feature that when present in a female, only offspring that inherit the element survive, a behavior that can lead to spread. Here, we derive equations that describe the conditions under which Medea elements with a fitness cost will spread, and the equilibrium allele frequencies are achieved. Of particular importance, we show that whenever Medea spreads, the non-Medea genotype is driven out of the population, and we estimate the number of generations required to achieve this goal for Medea elements with different fitness costs and male-only introduction frequencies. Finally, we characterize two contexts in which Medea elements with fitness costs drive the non-Medea allele from the population: an autosomal element in which not all Medea-bearing progeny of a Medea-bearing mother survive, and an X-linked element in species in which X/Y individuals are male. Our results suggest that Medea elements can drive population replacement under a wide range of conditions.     

The distribution and spread of naturally occurring Medea selfish genetic elements in the United States

Selfish genetic elements (SGEs) are DNA sequences that are transmitted to viable offspring in greater than Mendelian frequencies. Medea SGEs occur naturally in some populations of red flour beetle (Tribolium castaneum) and are expected to increase in frequency within populations and spread among populations. The large‐scale U.S. distributions of Medea‐4 (M⁴) had been mapped based on samples from 1993 to 1995. We sampled beetles in 2011–2014 and show that the distribution of M⁴ in the United States is dynamic and has shifted southward. By using a genetic marker of Medea‐1 (M¹), we found five unique geographic clusters with high and low M¹ frequencies in a pattern not predicted by microsatellite‐based analysis of population structure. Our results indicate the absence of rigid barriers to Medea spread in the United States, so assessment of what factors have limited its current distribution requires further investigation. There is great interest in using synthetic SGEs, including synthetic Medea, to alter or suppress pest populations, but there is concern about unpredicted spread of these SGEs and potential for populations to become resistant to them. The finding of patchy distributions of Medea elements suggests that released synthetic SGEs cannot always be expected to spread uniformly, especially in target species with limited dispersal.     

Meiotic drive in fungi: Chromosomal elements that cause fratricide and distort genetic ratios

Fungal Spore killers (Sk), studied most extensively inNeurospora and to a lesser extent inPodospora, Gibberella andCochliobolus, cause the death of ascospores (= meiospores) that do not contain the killer (Skk) element. When a Spore killer is heterozygous (SkK× Sks) inNeurospora, every ascus (= meiocyte) contains four normal-sized, black, viable ascospores (SkK), and four ascospores that are tiny, unpigmented and unviable (SKs). Killing of sensitive nuclei is expressed postmeiotically, and results in gross distortion of segregation ratios forSk-linked genes. A sensitive nucleus that would otherwise die is rescued if a killer nucleus is also enclosed in the same ascospore. InNeurospora, Sk is centromere-linked (linkage group III), and when heterozygous, shows a recombination block in a 30-map-unit region spanning the centromere of linkage group III. There is no ascospore death or recombination block in killer×killer or sensitive×sensitive crosses. Spore killers are fairly common inGibberella fujikuroi andNeurospora sitophila but extremely rare inN. intermedia, and have not yet been found among natural isolates ofN. crassa.     

Complex interactions between diverse mobile genetic elements drive the evolution of metal-resistant bacterial genomes

In this study, we compared the genomes of three metal-resistant bacteria isolated from mercury-contaminated soil. We identified diverse and novel MGEs with evidence of multiple LGT events shaping their genomic structure and heavy metal resistance. Among the three metal-resistant strains, Sphingobium sp SA2 and Sphingopyxis sp SE2 were resistant to multiple metals including mercury, cadmium, copper, zinc and lead. Pseudoxanthomonas sp SE1 showed resistance to mercury only. Whole genome sequencing by Illumina and Oxford Nanopore technologies was undertaken to obtain comprehensive genomic data. The Sphingobium and Sphingopyxis strains contained multiple chromosomes and plasmids, whereas the Pseudoxanthomonas strain contained one circular chromosome. Consistent with their metal resistance profiles, the strains of Sphingobium and Sphingopyxis contained a higher quantity of diverse metal resistance genes across their chromosomes and plasmids compared to the single-metal resistant Pseudoxanthomonas SE1. In all three strains, metal resistance genes were principally associated with various novel MGEs including genomic islands (GIs), integrative conjugative elements (ICEs), transposons, insertion sequences (IS), recombinase in trio (RIT) elements and group II introns, indicating their importance in facilitating metal resistance adaptation in a contaminated environment. In the Pseudoxanthomonas strain, metal resistance regions were largely situated on a GI. The chromosomes of the strains of Sphingobium and Sphingopyxis contained multiple metal resistance regions, which were likely acquired by several GIs, ICEs, numerous IS elements, several Tn3 family transposons and RIT elements. Two of the plasmids of Sphingobium were impacted by Tn3 family transposons and ISs likely integrating metal resistance genes. The two plasmids of Sphingopyxis harboured transposons, IS elements, an RIT element and a group II intron. This study provides a comprehensive annotation of complex genomic regions of metal resistance associated with novel MGEs. It highlights the critical importance of LGT in the evolution of metal resistance of bacteria in contaminated environments.     

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.     

Engineering the genomes of wild insect populations: Challenges, and opportunities provided by synthetic Medea selfish genetic elements

Advances in insect transgenesis and our knowledge of insect physiology and genomics are making it possible to create transgenic populations of beneficial or pest insects that express novel traits. There are contexts in which we may want the transgenes responsible for these traits to spread so that all individuals within a wild population carry them, a process known as population replacement. Transgenes of interest are unlikely to confer an overall fitness benefit on those who carry them. Therefore, an essential component of any population replacement strategy is the presence of a drive mechanism that will ensure the spread of linked transgenes. We discuss contexts in which population replacement might be desirable and the requirements a drive system must satisfy to be both effective and safe. We then describe the creation of synthetic Medea elements, the first selfish genetic elements synthesized de novo, with the capability of driving population replacement, in this case in Drosophila. The strategy used to create DrosophilaMedea is applicable to a number of other insect species and the Medea system satisfies key requirements for scientific and social acceptance. Finally, we highlight several challenges to implementing population replacement in the wild.     

Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution

Restriction–modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes.     

Small sperm,uniparental inheritance and selfish cytoplasmic elements: a comparison of two models

It has previously been suggested that small sperm size may be an adaptation to achieve uniparental inheritance of organelles, and hence to prevent the spread of selfish cytoplasmic elements. Such an explanation for anisogamy implies a mechanism whereby the male gamete eliminates its own cytoplasm prior to fusion with the egg. A model has been presented demonstrating the invasion and persistence of a modifier that acts gametically to kill its own organelles. Here we show, however, that this model is far from robust; indeed, if any cost is associated with the modifier it cannot persist. We also show that despite an empirically demonstrated association between anisogamy and multicellularity, this result also applies if the analysis is applied in the multicellular case. This class of model contrasts with the majority of analyses in which the modifier kills off the incoming gamete’s organelles. We show that these models are highly robust, even if uniparental inheritance is imperfect.     

Inverted repeats as genetic elements for promoting DNA inverted duplication: implications in gene amplification

Inverted repeats are important genetic elements for genome instability. In the current study we have investigated the role of inverted repeats in a DNA rearrangement reaction using a linear DNA substrate. We show that linear DNA substrates with terminal inverted repeats can efficiently transform Escherichia coli. The transformation products contain circular inverted dimers in which the DNA sequences between terminal inverted repeats are duplicated. In contrast to the recombination/rearrangement product of circular DNA substrates, which is exclusively one particular form of the inverted dimer, the rearrangement products of the linear DNA substrate consist of two isomeric forms of the inverted dimer. Escherichia coli mutants defective in RecBCD exhibit much reduced transformation efficiency, suggesting a role for RecBCD in the protection rather than destruction of these linear DNA substrates. These results suggest a model in which inverted repeats near the ends of a double-strand break can be processed by a helicase/exonuclease to form hairpin caps. Processing of hairpin capped DNA intermediates can then yield inverted duplications. Linear DNA substrates containing terminal inverted repeats can also be converted into inverted dimers in COS cells, suggesting conservation of this type of genome instability from bacteria to mammalian cells.     

Applying mobile genetic elements for genome analysis and evolution

Transposable elements (TEs) are ubiquitous components of all living organisms, and in the course of their coexistence with their respective host geneomes, these parasitc DNAs have played important roles in the evolution of complex genetic networks. The interaction between mobile DNAs and their host genomes are quite diverse, ranging from modifications of gene structure and regulation to alterations in general genome architecture. Thus during evolutionary time these elements can be regarded as natural molecular tools in shaping the organization, structure, and function of eukaryotic genes and genomes. Based on their intrinsic properties and features, mobile DNAs are widely applied at present as a technical “toolbox”, essential for studying a diverse spectrum of biological questions. In this review, we aim to summarize both the evolutionary impact of TEs on geneome evolution and their valuable and diverse methodological applications as molecular tools.     

Efficient and precise control of gene expression in Geobacter sulfurreducens through new genetic elements and tools for pollutant conversion

Geobacter species, exhibiting exceptional extracellular electron transfer aptitude, hold great potential for applications in pollution remediation, bioenergy production, and natural elemental cycles. Nonetheless, a scarcity of well-characterized genetic elements and gene expression tools constrains the effective and precise fine-tuning of gene expression in Geobacter species, thereby limiting their applications. Here, we examined a suite of genetic elements and developed a new genetic editing tool in Geobacter sulfurreducens to enhance their pollutant conversion capacity. First, the performances of the widely used inducible promoters, constitutive promoters, and ribosomal binding sites (RBSs) elements in G. sulfurreducens were quantitatively evaluated. Also, six native promoters with superior expression levels than constitutive promoters were identified on the genome of G. sulfurreducens. Employing the characterized genetic elements, the clustered regularly interspaced short palindromic repeats interference (CRISPRi) system was constructed in G. sulfurreducens to achieve the repression of an essential gene-aroK and morphogenic genes-ftsZ and mreB. Finally, applying the engineered strain to the reduction of tungsten trioxide (WO₃), methyl orange (MO), and Cr(VI), We found that morphological elongation through ftsZ repression amplified the extracellular electron transfer proficiency of G. sulfurreducens and facilitated its contaminant transformation efficiency. These new systems provide rapid, versatile, and scalable tools poised to expedite advancements in Geobacter genomic engineering to favor environmental and other biotechnological applications.     

Polyandry and the decrease of a selfish genetic element in a wild house mouse population

Despite deleterious effects on individuals, the t haplotype is a selfish genetic element present in many house mouse populations. By distorting the transmission ratio, +/t males transmit the t haplotype to up to 90% of their offspring. However, t/t individuals perish in utero. Theoretical models based on these properties predict a much higher t frequency than observed, leading to the t paradox. Here, we use empirical field data and theoretical approaches to investigate whether polyandry is a female counterstrategy against the negative fitness consequences of such distorters. We found a significant decrease of the t frequency over a period of 5.5 years that cannot be explained by the effect of transmission ratio distortion and recessive lethals, despite significantly higher life expectancy of +/t females compared to +/+ females. We quantified life-history data and homozygous and heterozygous fitness effects. Population subdivision and inbreeding were excluded as evolutionary forces influencing the t system. The possible influence of polyandry on the t system was then investigated by applying a stochastic model to this situation. Simulations show that polyandry can explain the observed t dynamics, making it a biologically plausible explanation for low t frequencies in natural populations in general.