Biology subjects

Lindholm, A. K.

Publications and source records attributed to Lindholm, A. K..

9 recordsLinked to original sources

bioRxiv2026

Assessing a natural gene drive for population control in house mice

House mice are a major invasive pest with significant impact on island ecosystems. Genetic biocontrol via gene editing offers promising new avenues for population control. An alternative idea dating back over half a century is to harness the unmodified, naturally occurring genetic element called t haplotype for population suppression. The t haplotype causes sterility in t/t homozygote males, while +/t heterozygote males transmit the t to most of their offspring via meiotic drive. We use population genetic modelling to systematically explore whether this approach can suppress invasive populations through the accumulation of t/t sterile males. We find that +/t fertile releases combined with the sustained release of t/t sterile males can achieve eradication, but require prolonged interventions, with eradication taking around 25 years under our baseline scenario. We then show that release effort and eradication times may be reduced substantially if releases are combined with trapping, culling, or the release of hyper-competitive (Adonis) males. A direct comparison with tCRISPR, currently the main engineered genetic biocontrol system for house mice, shows that the approach requires greater release effort but achieves comparable eradication times. We provide an R shiny application for exploring model scenarios interactively. Our findings highlight both the potential and the limitations of exploiting this natural meiotic drive system for population control, and identify key gaps in knowledge of mouse reproductive biology and behaviour needed to fully assess its feasibility in the field.

evolutionary biology↗

bioRxiv2024

Vocal communication is seasonal in social groups of wild, free-living house mice

House mice (Mus musculus domesticus) are among the most widely studied laboratory models of mammalian social behavior, yet we know relatively little about the ecology of their behaviors in natural environments. Here, we address this gap using radiotelemetry to track social interactions in a population of wild mice over 10 years, from 2013 to 2023, and interpret these interactions in the context of passive acoustic monitoring data collected from August 2022 until November 2023. Using deep convolutional neural networks, we identify 1.3 million individual vocalizations and align them in time with continuously collected telemetry data recording social interactions between individually identifiable mice. We find that vocalization is seasonal and correlated with long-term dynamics in features of social groups. In addition, we find that vocalization is closely associated in time with entrances to and exits from those groups, occurs most often in the presence of pups, and is correlated with how much time pairs of mice spend together. This work identifies seasonal patterns in the vocalizations of wild mice and lays a foundation to investigate the social role of acoustic communication in wild populations of a classic laboratory model organism.

animal behavior and cognition↗

bioRxiv2024

De novo assembly of the selfish t supergene reveals a deleterious evolutionary trajectory

Supergenes are linked clusters of DNA that are transmitted together due to rare or absent recombination. They undergo co-adaptation, allowing evolution to work on several genes to refine complex phenotypes, giving supergenes a competitive edge. Yet, due to their lack of recombination, supergenes are susceptible to deterioration as they cannot efficiently purge deleterious DNA. Few examples outside of sex chromosomes have been available for study. Here, we present the first assembly of the t haplotype, a 33.4 Mb supergene in house mice that selfishly transmits itself at non-Mendelian frequencies. We characterize the four large non-overlapping inversions that make up the t haplotype. We compare in a t/t individual two different t variants with different recessive lethal phenotypes (age at death). Despite that difference, they differ much less from each other than the rest of the chromosome. However, the differences that they have were much more likely to be deleterious than the differences between the two variants of the rest of the chromosome. We interpret this marked difference as evidence of the accumulation of deleterious variants, a hallmark of deterioration. The t region of chromosome 17 is more distant to the reference than the rest of the chromosome, and has a higher fraction of impactful differences here as well. Thus, we conclude that the t appears as a quickly spreading and deteriorating selfish supergene, a rare example of Mullers ratchet outside of sex chromosomes. Furthermore, we aim for our assembly to provide a resource for comparative work on the t haplotype, such as its evolutionary history.

evolutionary biology↗

bioRxiv2022

Two pup vocalization types are genetically and functionally separable in deer mice

Vocalization is a widespread vertebrate social behavior that is essential for fitness in the wild. While many vocal behaviors are highly conserved, heritable features of specific vocalization types can vary both within and between species, raising the questions of why and how some vocal behaviors evolve. Here, using new computational tools to automatically detect and cluster vocalizations into distinct acoustic categories, we compare pup isolation calls across neonatal development in eight taxa of deer mice (genus Peromyscus) and compare them to laboratory mice (C57Bl6/j strain) and free-living, wild house mice (Mus musculus musculus). Whereas both Peromyscus and Mus pups produce ultrasonic vocalizations (USVs), Peromyscus pups also produce a second call type with acoustic features, temporal rhythms, and developmental trajectories that are distinct from those of USVs. In deer mice, these tonal and low frequency "cries" are predominantly emitted in postnatal days one through nine, while USVs are primarily made after day nine. Using playback assays, we show that cries result in a more rapid approach by Peromyscus mothers than USVs, suggesting a role for cries in eliciting parental care early in neonatal development. Using genetic crosses between two sister species of deer mice exhibiting large, innate differences in the acoustic structure of cries and USVs, we find that variation in vocalization rate, duration, and pitch display different degrees of genetic dominance and that cry and USV features can be uncoupled in second-generation hybrids. Taken together, this work shows that vocal behavior can evolve quickly between closely related rodent species in which vocalization types, likely serving distinct functions in communication, are controlled by distinct genetic loci.

evolutionary biology↗

bioRxiv2021

Parent-offspring inference in highly inbred populations

Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obfuscate genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. Inbreeding is common in natural, domesticated, and experimental populations and genotyping of these populations often has more errors than in human datasets, so efficient methods for building pedigrees under these conditions are necessary. Here, we present a new method for parent-offspring inference in inbred pedigrees called SPORE (Specific Parent-Offspring Relationship Estimation). SPORE is vastly superior to existing pedigree-inference methods at detecting parent-offspring relationships, in particular when inbreeding is high or in the presence of genotyping errors, or both. SPORE therefore fills an important void in the arsenal of pedigree inference tools. Author SummaryKnowing the genealogical relationships among individuals is critical for genetic analyses, such as for identifying the mutations that cause diseases or that contribute to valuable agricultural traits such as milk production. Although many tools exist for establishing pedigrees using genetic information, these tools fail when individuals are highly inbred, such as in domesticated animals, or in groups of people in which consanguineous matings are common. Furthermore, existing tools do not work well when genetic information has errors at levels observed in modern datasets. Here, we present a novel approach to solve these problems. Our method is significantly more accurate than existing tools and more tolerant of errors in the genetic data. We expect that our method, which is simple to use and computationally efficient, will be a useful tool in a diversity of settings, from the studies of human and natural populations, to agricultural and experimental settings.

genetics↗

bioRxiv2021

Selfish migrants: How a meiotic driver is selected to increase dispersal

Meiotic drivers are selfish genetic elements that manipulate meiosis to increase their transmission to the next generation to the detriment of the rest of the genome. One example is the t haplotype in house mice, which is a naturally occurring meiotic driver with deleterious traits--poor fitness in polyandrous matings and homozygote inviability or infertility--that prevent its fixation. Recently, we discovered and validated a novel effect of t in a long-term field study on free-living wild house mice and with experiments: t-carriers are more likely to disperse. Here, we ask what known traits of the t haplotype can select for a difference in dispersal between t-carriers and wildtype mice. To that end, we built individual-based models with dispersal loci on the t and the homologous wildtype chromosomes. We also allow for density-dependent expression of these loci. The t haplotype consistently evolves to increase the dispersal propensity of its carriers, particularly at high densities. By examining variants of the model that modify different costs caused by t, we show that the increase in dispersal is driven by the deleterious traits of t, disadvantage in polyandrous matings and lethal homozygosity or male sterility. Finally, we show that an increase in driver-carrier dispersal can evolve across a range of values in driver strength and disadvantages.

evolutionary biology↗

bioRxiv2021

Family dynamics reveal that female house mice preferentially breed in their maternal community

Whether females breed in their natal group is an important factor in the evolution of extended families in animal sociality. Breeding in natal groups comes with clear costs and benefits, depending on size of the group and presence of older relatives, including mothers. Studying individual decisions about whether to stay or leave can provide insight into the mechanisms and trade-offs governing the formation and structure of family groups. We investigated the family dynamics of a large population of free-ranging commensal house mice. Using dynamic community detection on long term datasets, we determined which females first bred in their natal group. We then looked at how this influenced breeding success. We found most females (77%) exhibited strong philopatry, breeding in their natal groups. Whether a female bred elsewhere was only predictable when natal groups were extremely small and related or large and unrelated. Despite this preference, breeding elsewhere made no difference in how quickly and successfully a female bred. However, presence of their mother did lead females to breed sooner when born during high breeding activity, when competition over reproduction is high. Based on these results, potential loss of fitness does not seem to be the main driver of philopatry in female house mice. The effect of the presence of mothers may indicate retaining prior social connections is an important benefit of breeding in the natal group. Mothers providing benefits also suggests lack of conflict between generations, which is likely an important attribute in the development of extended family groups. Lay summaryWhether animals breed in the group they are born in influences how they form extended family groups. Whether females stay will depend on properties such as presence of older relatives, including mothers. Using long-term wild mouse data, we track groups and which group females bred in. Most stayed, but leaving didnt reduce breeding success. Presence of mother, who generally stayed, did lead to earlier breeding. This might be a key advantage to remaining to breed.

animal behavior and cognition↗

bioRxiv2020

Population density and temperature influence the return on maternal investment in wild house mice

In mammals, reproduction is influenced by competitive stress, temperature and food availability and these factors might be crucial already during early life. Favourable early life environment and high maternal investment are expected to improve survival and reproduction. In mammals, maternal investment via lactation predicts offspring growth. As body mass is often associated with fitness consequences, females have the potential to influence offspring fitness through their level of investment, which might interact with effects of population density and temperature. Here, we investigate the relationship between pup body mass at day 13 (used as approximation for weaning mass) and individual reproductive parameters as well as longevity under natural variation in population density and temperatures. Further, we assess the extent to which mothers influence the body mass of their offspring until weaning. We analysed life data of 384 house mice (Mus musculus domesticus) from a free-living wild population that was not food limited. We found a complex effect of population density, temperature and maternal investment on life-history traits related to fitness: Shorter longevity with increasing pup body mass at day 13; delayed reproduction of heavier pups when raised at warmer temperatures; and increased lifetime reproductive success for heavier pups at high densities. House mice could use population density and temperature as cues for predicting future environmental conditions, allowing a mother to adjust her investment according to the environment in which offspring will breed in order to maximise fitness. This study highlights the importance of considering ecological conditions in combination with maternal effects.

evolutionary biology↗

bioRxiv2018

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

Life 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 hosts 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 hosts 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.

evolutionary biology↗