Biology subjects

Runge, J.-N.

Publications and source records attributed to Runge, J.-N..

4 recordsLinked to original sources

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↗

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↗

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↗