Biology subjects

Purcell, J.

Publications and source records attributed to Purcell, J..

8 recordsLinked to original sources

bioRxiv2026

Gene flux drives functional changes in an ancient supergene in Formica lemani

Pinpointing the genetic elements underlying a phenotype within a supergene can be difficult because hundreds of linked genes can show similar associations with phenotype. Rare recombination between supergene haplotypes can help identify those genetic elements by changing haplotype-phenotype combinations. Here we investigate the genetic underpinnings of colony queen number and body size in the ant Formica lemani. Throughout the Formica genus, single-queen colonies typically carry M haplotypes, while multi-queen colonies also carry P haplotypes. In F. lemani, we found two P haplotypes homologous to those described in the closely related F. cinerea, but unlike in F. cinerea, where P1 is restricted to multi-queen colonies, F. lemani P1 is common in both single- and multi-queen colonies. This deviation suggests that P1 may carry novel SNP combinations allowing single queen colony compatibility. By comparing haplotypes within F. lemani and with Formica cinerea, we searched for candidate monogyny variants resulting from gene flux from the M onto the P1 haplotype, or with P1-specific mutations. We found 82 genes associated with candidate variants, of which two are among the fourteen previously suggested candidates in other species, suggesting that several different genes may underlie queen number across the genus. We also identified a supergene associated with smaller queens and males, which is shared with F. cinerea and in interchromosomal linkage disequilibrium with the queen-number supergene. Together, these results provide a rare example of how an ancient supergene can change in function, and a step toward identifying the genes within a supergene responsible for its functions.

evolutionary biology↗

bioRxiv2026

Beyond queen number: two supergenes coordinate dispersal, mating, and colony founding in the ant Formica cinerea

Reproductive success often depends on coordinated combinations of morphology, dispersal ability, and mating behavior. Supergenes, genomic regions of suppressed recombination, allow such combinations to be inherited by offspring as a single unit. In ants, independently evolved supergenes control colony queen number, yet few studies have investigated their joint influence on morphology, mating, and colony-founding in sexuals. Formica cinerea provides a unique opportunity to address this question because it harbors two supergenes that together produce three queen and male morphs: large monogyne, large polygyne, and small polygyne. Here we show that these supergenes jointly shape an integrated suite of traits across the reproductive cycle. Wing area was primarily associated with the chromosome 3 supergene, with monogyne individuals having larger wings than polygyne individuals. Thorax volume was associated with the chromosome 9 supergene, with small polygyne individuals having reduced thorax volume regardless of social origin. Mating was assortative for both supergenes in large morphs but random in small polygyne queens. Independent colony founding was almost exclusively performed by large monogyne queens; initial egg production was unaffected by mate genotype. These findings show that the two supergenes jointly coordinate dispersal morphology, mate choice, and colony-founding into coherent reproductive strategies, preventing maladaptive intermediate phenotypes.

evolutionary biology↗

bioRxiv2026

Lethal epistasis maintains strong linkage disequilibrium between unlinked supergenes

Linkage disequilibrium (LD) between adaptive gene combinations is typically maintained through physical linkage and suppressed recombination. Although epistatic interactions can maintain LD between unlinked loci, this mechanism is rarely documented in nature. Supergenes, regions of suppressed recombination containing tightly linked loci, typically exemplify the first mechanism, in which genomic rearrangements lock together coadapted alleles. Here, we demonstrate a rare case of epistasis-driven LD between two supergenes on different chromosomes in the European ant Formica cinerea: one controlling colony queen number (chromosome 3) and another determining sexual body size (chromosome 9). We show that these supergenes assort independently according to Mendelian expectations during meiosis, yet exhibit high LD between the multi-queen haplotype P2 and the miniaturizing haplotype 9r, with small queens and males occurring exclusively in multi-queen colonies. Mismatched genotype combinations (P2 without 9r and vice versa) are severely underrepresented among all adult castes, with mismatched males experiencing complete mortality. We show that this pattern cannot be explained by meiotic drive or maternal-effect killing, assortative mating, or extrinsic selection on adults, indicating strong postzygotic epistatic selection maintaining the observed LD. The fitness costs of these epistatic interactions are substantial but critically depend on mating combinations: heterozygous small queens achieve 1.5-2.5 times higher fitness (based on offspring genotype viability) when mated to small males (P2-9r) compared to large males. Our findings provide empirical evidence for epistatic interactions between unlinked supergenes maintaining LD in the absence of physical linkage.

evolutionary biology↗

bioRxiv2025

Multiple origins of a sex ratio supergene in Formica ants

Many known supergenes, regions of the genome containing two or more functional mutations with little or no recombination between them, formed in recent evolutionary time to control complex traits. However, when supergenes persist through millions of years of evolution, they may take on additional functions in different lineages. Here, we investigate how an ancient supergene has evolved to gain novel function. In Formica ants, most species have an ancient "social" supergene with M and P haplotypes which determine whether a colony is headed by a single queen or multiple queens, respectively. At least three Formica species have an additional haplotype on the same chromosome, termed MD, associated with female-biased offspring sex ratio at the colony level. Is an MD haplotype present in additional species? Do the MD haplotypes share a common origin or did they evolve convergently? With whole-genome resequencing, we identify MD haplotypes in three additional species and use variation across six Formica species to examine the evolutionary history of the MD haplotype. We find that the MD haplotype did not originate from a rearrangement of the ancestral M haplotype. Instead, the MD haplotype likely originated from recombination between the M and P haplotypes. Strikingly, we identified two putative origins of the MD haplotype, one in the ancestor of five Nearctic species, and a second in the Palearctic species F. cinerea. The discovery of two MD haplotypes convergently evolving from distinct recombination events between two ancestral supergene haplotypes illustrates how supergenes can diversify and gain additional phenotypes.

genomics↗

bioRxiv2025

Variation in social organization and supergene control along a latitudinal gradient

Widespread species often experience vastly different environmental conditions across their range. In species with polymorphic traits under strong genetic control, we can investigate how environmental variation influences the distribution of traits and whether the strength of genetic control is consistent across environmental gradients. Here, we investigate the distribution of phenotypic and genetic variation in the ant Formica podzolica across 30{degrees} of latitude. This species shares a supergene that is associated with colony queen number and colony sex ratio with other congeners, but we detect a surprising six common supergene variants. Colonies with a single queen are more abundant in the north compared to those with multiple queens, although the queen number polymorphism is present throughout the range. In parallel, the frequency of supergene haplotypes also varies with latitude. Of the 170 colonies examined, 10.6% contained supergene haplotypes that did not match the queen number phenotype. The highest concentration of these mismatched colonies occurred in one site, raising the possibility that the environmental conditions there override supergene function. While the supergene system in F. podzolica is complex, this species holds promise for understanding how an ancient supergene system evolves in a single species experiencing highly variable environmental conditions.

evolutionary biology↗

bioRxiv2023

PARG inhibition induces nuclear aggregation of PARylated PARP1

PARG inhibitors are currently under clinical development for the treatment of DNA repair-deficient cancers, however, their precise mechanism of action is still unclear. Here we report that PARG inhibition causes increased nuclear PARylated PARP1 that limits PARP1 chromatin binding in response to DNA damage. This PARylated PARP1 accumulates as aggregates at sites distinct from the site of DNA damage, leading to the mis-localization of PARP1. Additionally, these aggregates are formed through PAR chains as abrogating PARP1 catalytic activity prevents their formation. Finally, these PARP1 nuclear aggregates persist long-term and are associated with cleaved cytoplasmic PARP1, a cell death hallmark, which ultimately leads to a non-apoptotic form of cell death. Overall, our data uncovers a novel mechanism of PARG inhibitor cytotoxicity, which will inform ongoing clinical studies.

cancer biology↗

bioRxiv2023

Does social antagonism facilitate supergene expansion? A novel region of suppressed recombination in a 4-haplotype supergene system.

Models of both sex chromosome evolution and the genetic basis of local adaptation suggest that selection acts to lock beneficial combinations of alleles together in regions of reduced or suppressed recombination. Drawing inspiration from such models, we apply similar logic to investigate whether an autosomal supergene underlying colony social organization in ants expanded to include "socially antagonistic" alleles. We tested this premise in a Formica ant species wherein we identified four supergene haplotypes on chromosome 3 underlying colony social organization and sex ratio. Remarkably, we discovered a novel rearranged supergene variant (9r) on chromosome 9 underlying queen miniaturization. The 9r is tightly linked to one of the haplotypes (P2) on chromosome 3, found predominantly in multi-queen (polygyne) colonies. We suggest that queen miniaturization is strongly disfavored in the single queen (monogyne) background, and thus socially antagonistic. As such, divergent selection experienced by ants living in alternative social environments (monogyne and polygyne) may have contributed to the emergence of a genetic polymorphism on chromosome 9 and associated queen size dimorphism. Consequently, an ancestral polygyne-associated haplotype may have expanded to include the polymorphism on chromosome 9, resulting in a larger region of suppressed recombination spanning two chromosomes. This process is analogous to the formation of neo-sex chromosomes and consistent with models of expanding regions of suppressed recombination. We also propose that miniaturized queens, 16-20% smaller than queens without 9r, could be incipient intraspecific social parasites. Significance statementWhen sets of gene variants work well together, selection may lead to a reduction in recombination between them. Here, we discover a novel supergene region on chromosome 9 that controls a previously undescribed queen size polymorphism in Formica cinerea ants. The haplotype that is found in small queens, 9r, is tightly linked to a supergene haplotype on chromosome 3 that is found in multi-queen colonies. We propose that the region of suppressed recombination expanded to include both chromosome 3 and chromosome 9 because small queens could be successful in the multi-queen but not in the single-queen environment.

evolutionary biology↗

bioRxiv2021

Linked supergenes underlie split sex ratio and social organization in an ant

Sexually reproducing organisms usually invest equally in male and female offspring. Deviations from this pattern have led researchers to new discoveries in the study of parent-offspring conflict, genomic conflict, and cooperation. Some social insect species exhibit the unusual population-level pattern of split sex ratio, wherein some colonies specialize in the production of future queens and others specialize in the production of males. Theoretical work focused on the relatedness asymmetries emerging from haplodiploid inheritance, whereby queens are equally related to daughters and sons, but their daughter workers are more closely related to sisters than to brothers, led to a series of testable predictions and spawned many empirical studies of this phenomenon. However, not all empirical systems follow predicted patterns, so questions remain about how split sex ratio emerges. Here, we sequence the genomes of 138 Formica glacialis workers from 34 male-producing and 34 gyne-producing colonies to determine whether split sex ratio is under genetic control. We identify a supergene spanning 5.5 Mbp that is closely associated with sex allocation in this system. Strikingly, this supergene is adjacent to another supergene spanning 5 Mbp that is associated with variation in colony queen number. We identify a similar pattern in a second related species, Formica podzolica. The discovery that split sex ratio is determined, at least in part, by a supergene in two species opens a new line of research on the evolutionary drivers of split sex ratio. Significance StatementSome social insects exhibit split sex ratio, wherein some colonies produce future queens and others produce males. This phenomenon spawned many influential theoretical studies and empirical tests, both of which have advanced our understanding of parent-offspring conflicts and cooperation. However, some empirical systems did not follow theoretical predictions, indicating that researchers lack a comprehensive understanding of the drivers of split sex ratio. Here, we show that split sex ratio is associated with a large genomic region in two ant species. The discovery of a genetic basis for sex allocation in ants provides a novel explanation for this phenomenon, particularly in systems where empirical observations deviate from theoretical predictions.

evolutionary biology↗