Carrying a selfish genetic element predicts increased migration propensity in free-living wild house mice

Life is built on cooperation between genes, which makes it vulnerable to parasitism. Selfish genetic elements that exploit this cooperation can achieve large fitness gains by increasing their transmission relative to the rest of the genome. This leads to counter-adaptations that generate unique selection pressures on the selfish genetic element. This arms race is similar to host–parasite coevolution, as some multi-host parasites alter the host’s behaviour to increase the chance of transmission to the next host. Here, we ask if, similarly to these parasites, a selfish genetic element in house mice, the t haplotype, also manipulates host behaviour, specifically the host’s migration propensity. Variants of the t that manipulate migration propensity could increase in fitness in a meta-population. We show that juvenile mice carrying the t haplotype were more likely to emigrate from and were more often found as migrants within a long-term free-living house mouse population. This result may have applied relevance as the t has been proposed as a basis for artificial gene drive systems for use in population control.

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The t haplotype, a selfish genetic element, manipulates migration propensity in free-living wild house mice Mus musculus domesticus

10.1101/271247 ◽

2018 ◽

Author(s):

Jan-Niklas Runge ◽

Anna K. Lindholm

Keyword(s):

Population Control ◽

House Mice ◽

Gene Drive ◽

Genetic Element ◽

Mus Musculus Domesticus ◽

Free Living ◽

Mouse Population ◽

Selfish Genetic Elements ◽

Selfish Genetic Element ◽

Migration Propensity

AbstractLife is built on cooperation between genes, which makes it vulnerable to parasitism. However, selfish genetic elements that exploit this cooperation can achieve large fitness gains by increasing their transmission unfairly relative to the rest of the genome. This leads to counter-adaptations that generate unique selection pressures on the selfish genetic element. This arms race is similar to host-parasite co-evolution. Some multi-host parasites alter the host’s behaviour to increase the chance of transmission to the next host. Here we ask if, similarly to these parasites, a selfish genetic element in house mice, the t haplotype, also manipulates host behaviour, specifically the host’s migration propensity. Variants of the t that manipulate migration propensity could increase in fitness in a meta-population. We show that juvenile mice carrying the t haplotype were more likely to emigrate from and were more often found as migrants within a long-term free-living house mouse population. This result may have applied relevance as the t has been proposed as a basis for artificial gene drive systems for use in population control.

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A longitudinal study of phenotypic changes in early domestication of house mice

Royal Society Open Science ◽

10.1098/rsos.172099 ◽

2018 ◽

Vol 5 (3) ◽

pp. 172099 ◽

Cited By ~ 17

Author(s):

Madeleine Geiger ◽

Marcelo R. Sánchez-Villagra ◽

Anna K. Lindholm

Keyword(s):

Longitudinal Study ◽

Experimental Studies ◽

House Mice ◽

Free Living ◽

Mouse Population ◽

Domestication Syndrome ◽

Phenotypic Changes ◽

Wild House Mice ◽

Term Data

Similar phenotypic changes occur across many species as a result of domestication, e.g. in pigmentation and snout size. Experimental studies of domestication have concentrated on intense and directed selection regimes, while conditions that approximate the commensal and indirect interactions with humans have not been explored. We examine long-term data on a free-living population of wild house mice that have been indirectly selected for tameness by regular exposure to humans. In the course of a decade, this mouse population exhibited significantly increased occurrence of white patches of fur and decreased head length. These phenotypic changes fit to the predictions of the ‘domestication syndrome'.

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A selfish genetic element linked to increased lifespan impacts metabolism in female house mice

Journal of Experimental Biology ◽

10.1242/jeb.212704 ◽

2019 ◽

Vol 223 (1) ◽

pp. jeb212704

Author(s):

Patricia C. Lopes ◽

Anna K. Lindholm

Keyword(s):

House Mice ◽

Genetic Element ◽

Selfish Genetic Element

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Experiments confirm a dispersive phenotype associated with a natural gene drive system

Royal Society Open Science ◽

10.1098/rsos.202050 ◽

2021 ◽

Vol 8 (5) ◽

Author(s):

Jan-Niklas Runge ◽

Anna K. Lindholm

Keyword(s):

Sperm Competition ◽

Local Density ◽

House Mice ◽

Gene Drive ◽

Wild Type ◽

Fitness Costs ◽

Oestrus Cycle ◽

Drive Systems ◽

Average Body ◽

Average Body Weight

Meiotic drivers are genetic entities that increase their own probability of being transmitted to offspring, usually to the detriment of the rest of the organism, thus ‘selfishly’ increasing their fitness. In many meiotic drive systems, driver-carrying males are less successful in sperm competition, which occurs when females mate with multiple males in one oestrus cycle (polyandry). How do drivers respond to this selection? An observational study found that house mice carrying the t haplotype, a meiotic driver, are more likely to disperse from dense populations. This could help the t avoid detrimental sperm competition, because density is associated with the frequency of polyandry. However, no controlled experiments have been conducted to test these findings. Here, we confirm that carriers of the t haplotype are more dispersive, but we do not find this to depend on the local density. t -carriers with above-average body weight were particularly more likely to disperse than wild-type mice. t -carrying mice were also more explorative but not more active than wild-type mice. These results add experimental support to the previous observational finding that the t haplotype affects the dispersal phenotype in house mice, which supports the hypothesis that dispersal reduces the fitness costs of the t .

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Evolutionary dynamics of CRISPR gene drives

10.1101/057281 ◽

2016 ◽

Cited By ~ 10

Author(s):

Charleston Noble ◽

Jason Olejarz ◽

Kevin M. Esvelt ◽

George M. Church ◽

Martin A. Nowak

Keyword(s):

Evolutionary Dynamics ◽

Evolutionary Stability ◽

Clear Understanding ◽

Gene Drive ◽

Host Organism ◽

Wild Populations ◽

Selfish Genetic Elements ◽

Real World Applications ◽

Drive Systems ◽

Gene Drives

AbstractThe alteration of wild populations has been discussed as a solution to a number of humanity’s most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, CRISPR gene drives, selfish genetic elements which can spread through populations even if they confer no advantage to their host organism, are rapidly emerging as the most promising approach. But before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design which selects against resistant alleles greatly improves evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights which inform the engineering of practical gene drive systems.

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Polyandry blocks gene drive in a wild house mouse population

Nature Communications ◽

10.1038/s41467-020-18967-8 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Andri Manser ◽

Barbara König ◽

Anna K. Lindholm

Keyword(s):

Natural Populations ◽

Reproductive Behaviour ◽

Mendelian Inheritance ◽

House Mice ◽

Gene Drive ◽

Mouse Population ◽

Drive Frequency ◽

Wild House Mice ◽

The Impact ◽

Wild House Mouse

Abstract Gene drives are genetic elements that manipulate Mendelian inheritance ratios in their favour. Understanding the forces that explain drive frequency in natural populations is a long-standing focus of evolutionary research. Recently, the possibility to create artificial drive constructs to modify pest populations has exacerbated our need to understand how drive spreads in natural populations. Here, we study the impact of polyandry on a well-known gene drive, called t haplotype, in an intensively monitored population of wild house mice. First, we show that house mice are highly polyandrous: 47% of 682 litters were sired by more than one male. Second, we find that drive-carrying males are particularly compromised in sperm competition, resulting in reduced reproductive success. As a result, drive frequency decreased during the 4.5 year observation period. Overall, we provide the first direct evidence that the spread of a gene drive is hampered by reproductive behaviour in a natural population.

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Cleave and Rescue, a novel selfish genetic element and general strategy for gene drive

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1816928116 ◽

2019 ◽

Vol 116 (13) ◽

pp. 6250-6259 ◽

Cited By ~ 47

Author(s):

Georg Oberhofer ◽

Tobin Ivy ◽

Bruce A. Hay

Keyword(s):

Essential Gene ◽

Drosophila Virilis ◽

General Strategy ◽

Gene Drive ◽

Genetic Element ◽

Guide Rnas ◽

Selfish Genetic Element ◽

Diverse Species ◽

Dependent Inactivation ◽

Beneficial Traits

There is great interest in being able to spread beneficial traits throughout wild populations in ways that are self-sustaining. Here, we describe a chromosomal selfish genetic element,CleaveR[Cleave and Rescue (ClvR)], able to achieve this goal.ClvRcomprises two linked chromosomal components. One, germline-expressed Cas9 and guide RNAs (gRNAs)—the Cleaver—cleaves and thereby disrupts endogenous copies of a gene whose product is essential. The other, a recoded version of the essential gene resistant to cleavage and gene conversion with cleaved copies—the Rescue—provides essential gene function.ClvRenhances its transmission, and that of linked genes, by creating conditions in which progeny lackingClvRdie because they have no functional copies of the essential gene. In contrast, those who inheritClvRsurvive, resulting in an increase inClvRfrequency.ClvRis predicted to spread to fixation under diverse conditions. To test these predictions, we generated aClvRelement inDrosophila melanogaster.ClvRtkois located on chromosome 3 and uses Cas9 and four gRNAs to disruptmelanogaster technical knockout(tko), an X-linked essential gene. Rescue activity is provided bytkofromDrosophila virilis.ClvRtkoresults in germline and maternal carryover-dependent inactivation ofmelanogaster tko(>99% per generation); lethality caused by this loss is rescued by thevirilistransgene;ClvRtkoactivities are robust to genetic diversity in strains from five continents; and uncleavable but functionalmelanogaster tkoalleles were not observed. Finally,ClvRtkospreads to transgene fixation. The simplicity ofClvRsuggests it may be useful for altering populations in diverse species.

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Suppression gene drive in continuous space can result in unstable persistence of both drive and wild-type alleles

10.1101/769810 ◽

2019 ◽

Cited By ~ 7

Author(s):

Jackson Champer ◽

Isabel Kim ◽

Samuel E. Champer ◽

Andrew G. Clark ◽

Philipp W. Messer

Keyword(s):

Natural Populations ◽

Spatial Models ◽

Ecological Factors ◽

Natural Environments ◽

Gene Drive ◽

Wild Type ◽

Lower Efficiency ◽

Continuous Space ◽

Selfish Genetic Elements ◽

Drive Systems

ABSTRACTRapid evolutionary processes can produce drastically different outcomes when studied in panmictic population models versus spatial models where the rate of evolution is limited by dispersal. One such process is gene drive, which allows “selfish” genetic elements to quickly spread through a population. Engineered gene drive systems are being considered as a means for suppressing disease vector populations or invasive species. While laboratory experiments and modeling in panmictic populations have shown that such drives can rapidly eliminate a population, it is not yet clear how well these results translate to natural environments where individuals inhabit a continuous landscape. Using spatially explicit simulations, we show that instead of population elimination, release of a suppression drive can result in what we term “chasing” dynamics. This describes a condition in which wild-type individuals quickly recolonize areas where the drive has locally eliminated the population. Despite the drive subsequently chasing the wild-type allele into these newly re-colonized areas, complete population suppression often fails or is substantially delayed. This delay increases the likelihood that the drive becomes lost or that resistance evolves. We systematically analyze how chasing dynamics are influenced by the type of drive, its efficiency, fitness costs, as well as ecological and demographic factors such as the maximal growth rate of the population, the migration rate, and the level of inbreeding. We find that chasing is generally more common for lower efficiency drives and in populations with low dispersal. However, we further find that some drive mechanisms are substantially more prone to chasing behavior than others. Our results demonstrate that the population dynamics of suppression gene drives are determined by a complex interplay of genetic and ecological factors, highlighting the need for realistic spatial modeling to predict the outcome of drive releases in natural populations.

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Detrimental effects of an autosomal selfish genetic element on sperm competitiveness in house mice

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.0974 ◽

2015 ◽

Vol 282 (1811) ◽

pp. 20150974 ◽

Cited By ~ 39

Author(s):

Andreas Sutter ◽

Anna K. Lindholm

Keyword(s):

Multiple Mating ◽

Sperm Quality ◽

House Mice ◽

Wild Type ◽

Genetic Incompatibility ◽

Selfish Genetic Elements ◽

Selfish Genetic Element ◽

Mating Order ◽

Evolutionary Force ◽

Vertebrate Model

Female multiple mating (polyandry) is widespread across many animal taxa and indirect genetic benefits are a major evolutionary force favouring polyandry. An incentive for polyandry arises when multiple mating leads to sperm competition that disadvantages sperm from genetically inferior mates. A reduction in genetic quality is associated with costly selfish genetic elements (SGEs), and studies in invertebrates have shown that males bearing sex ratio distorting SGEs are worse sperm competitors than wild-type males. We used a vertebrate model species to test whether females can avoid an autosomal SGE, the t haplotype, through polyandry. The t haplotype in house mice exhibits strong drive in t heterozygous males by affecting spermatogenesis and is associated with homozygous in utero lethality. We used controlled matings to test the effect of the t haplotype on sperm competitiveness. Regardless of mating order, t heterozygous males sired only 11% of zygotes when competing against wild-type males, suggesting a very strong effect of the t haplotype on sperm quality. We provide, to our knowledge, the first substantial evidence that polyandry ameliorates the harmful effects of an autosomal SGE arising through genetic incompatibility. We discuss potential mechanisms in our study species and the broader implications for the benefits of polyandry.

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