Biology subjects

Moore, E. C.

Publications and source records attributed to Moore, E. C..

12 recordsLinked to original sources

bioRxiv2024

Trophic level associated gut length divergence evolved under sexual conflict in Lake Malawi cichlids

Variation in gastrointestinal morphology is associated with dietary specialization across the animal kingdom. Gut length generally correlates with trophic level, and increased gut length in herbivores is a classic example of adaptation to cope with diets with lower nutrient content and a higher proportion of refractory material. However, the genetic basis of gut length variation remains largely unstudied, partly due to the inaccessibility and plasticity of the gut tissue, as well as the lack of dietary diversity within traditional model organisms relative to that observed among species belonging to different trophic levels. Here, we confirm the genetic basis of gut length variation among recently evolved Lake Malawi cichlid fish species with different dietary adaptations. We then produce interspecific, inter-trophic-level hybrids to map evolved differences in intestinal length in an F2 mapping cross between Metriaclima mbenjii, an omnivore with a relatively long gut, and Aulonocara koningsi, a carnivore with a relatively short gut. We identify numerous candidate quantitative trait loci for evolved differences in intestinal length. These quantitative trait loci are predominantly sex-specific, supporting an evolutionary history of sexual conflicts for the gut. We also identify epistatic interactions potentially associated with canalization and the maintenance of cryptic variation in the cichlid adaptive radiation. Overall, our results suggest a complex, polygenic evolution of gut length variation associated with trophic level differences among cichlids, as well as conflicts and interactions that may be involved in evolutionary processes underlying other traits in cichlids. SummaryThis study examines the genetic basis of gut length variation in Lake Malawi cichlids, which exhibit different dietary adaptations. It highlights how cichlids recapitulate a broad taxonomic trend: gut length correlates with trophic level, with herbivores and omnivores having longer intestines than carnivores. By creating hybrids of Metriaclima mbenjii (omnivore) and Aulonocara koningsi (carnivore), we identify several quantitative trait loci and epistatic interactions underlying gut length differences. These genetic associations are predominantly sex-specific, suggesting historical sexual conflicts. The results indicate complex, polygenic evolution of gut morphology in these fish, and suggest evolutionary interactions and processes shaping dietary traits across species.

genetics↗

bioRxiv2023

Different complex regulatory phenotypes underlie hybrid male sterility in divergent rodent crosses

Hybrid incompatibilities are a critical component of species barriers and may arise due to negative interactions between divergent regulatory elements in parental species. We used a comparative approach to identify common themes in the regulatory phenotypes associated with hybrid male sterility in two divergent rodent crosses, dwarf hamsters and house mice. We investigated three potential characteristic gene expression phenotypes in hybrids including the propensity of transgressive differentially expressed genes towards over or underexpression, the influence of developmental stage on patterns of misexpression, and the role of the sex chromosomes on misexpression phenotypes. In contrast to near pervasive overexpression in hybrid house mice, we found that misexpression in hybrid dwarf hamsters was dependent on developmental stage. In both house mouse and dwarf hamster hybrids, however, misexpression increased with the progression of spermatogenesis, although to varying extents and with potentially different consequences. In both systems, we detected sex-chromosome specific overexpression in stages of spermatogenesis where inactivated X chromosome expression was expected, but the hybrid overexpression phenotypes were fundamentally different. Importantly, misexpression phenotypes support the presence of multiple developmental blocks to spermatogenesis in dwarf hamster hybrids, including a potential role of meiotic stalling or breakdown early in spermatogenesis. Collectively, we demonstrate that while there are some similarities in hybrid expression phenotypes of house mice and dwarf hamsters, there are also clear differences that point towards unique mechanisms underlying hybrid male sterility. Our results highlight the potential of comparative approaches in helping to understand the causes and consequences of disrupted gene expression in speciation.

evolutionary biology↗

bioRxiv2023

Distinct genetic origins of eumelanin intensity and barring patterns in cichlid fishes

Pigment patterns are incredibly diverse across vertebrates and are shaped by multiple selective pressures from predator avoidance to mate choice. A common pattern across fishes, but for which we know little about the underlying mechanisms, is repeated melanic vertical bars. In order to understand genetic factors that modify the level or pattern of vertical barring, we generated a genetic cross of 322 F2 hybrids between two cichlid species with distinct barring patterns, Aulonocara koningsi and Metriaclima mbenjii. We identify 48 significant quantitative trait loci that underlie a series of seven phenotypes related to the relative pigmentation intensity, and four traits related to patterning of the vertical bars. We find that genomic regions that generate variation in the level of eumelanin produced are largely independent of those that control the spacing of vertical bars. Candidate genes within these intervals include novel genes and those newly-associated with vertical bars, which could affect melanophore survival, fate decisions, pigment biosynthesis, and pigment distribution. Together, this work provides insights into the regulation of pigment diversity, with direct implications for an animals fitness and the speciation process.

evolutionary biology↗

bioRxiv2022

Adaptive structural and functional evolution of the placenta protects fetal growth in high elevation deer mice

Environmental hypoxia challenges female reproductive physiology in placental mammals, increasing rates of gestational complications. Adaptation to high elevation has limited many of these effects in humans and other mammals, offering potential insight into the developmental processes that lead to and protect against hypoxia-related gestational complications. However, our understanding of these adaptations has been hampered by a lack of experimental work linking the functional, regulatory, and genetic underpinnings of gestational development in locally-adapted populations. Here, we dissect high-elevation adaptation in the reproductive physiology of deer mice, (Peromyscus maniculatus), a rodent species with an exceptionally broad elevational distribution that has emerged as a model for hypoxia adaptation. Using experimental acclimations, we show that lowland mice experience pronounced fetal growth restriction when challenged with gestational hypoxia, while highland mice maintain normal growth by expanding the compartment of the placenta that facilitates nutrient and gas exchange between dam and fetus. We then use compartmentspecific transcriptome analyses to show that adaptive structural remodeling of the placenta is coincident with widespread changes in gene expression within this same compartment. Genes associated with fetal growth in deer mice significantly overlap with genes involved in human placental development, pointing to conserved or convergent pathways underlying these processes. Finally, we overlay our results with genetic data from natural populations to identify can-didate genes and genomic features that contribute to these placental adaptations. Collectively, these experiments advance our understanding of adaptation to hypoxic environments by revealing physiological and genetic mechanisms that shape fetal growth trajectories under maternal hypoxia. Significance StatementResidence at high elevations is associated with higher risk pregnancies and low birth weight, yet the causal mechanisms remain poorly understood. Using a high elevation-adapted rodent model, we investigated the physiological traits that explain fetal growth trajectories in low oxygen environments, and how evolutionary adaptation has modified these traits. We showed that high- and low-elevation populations of deer mice differ in their susceptibility to fetal growth restriction during gestational hypoxia and that these population-level differences are associated with structural and transcriptomic changes in the placenta. We further link placental gene expression to genomic features under selection at high elevation. Our findings identify adaptations that are likely relevant to offsetting the effects of hypoxia on fetal and placental development across mammals.

evolutionary biology↗

bioRxiv2022

A natural variation-based screen in mouse cells reveals USF2 as a regulator of the DNA damage response and cellular senescence

Cellular senescence is a program of cell cycle arrest, apoptosis resistance, and cytokine release induced by stress exposure in metazoan cells. Landmark studies in laboratory mice have characterized a number of master senescence regulators, including p16INK4a, p21, NF-kB, p53, and C/EBP{beta}. To discover other molecular players in senescence, we developed a screening approach to harness the evolutionary divergence between mouse species. We found that primary cells from the Mediterranean mouse Mus spretus, when treated with DNA damage to induce senescence, produced less cytokine and had less-active lysosomes than cells from laboratory M. musculus. We used allele-specific expression profiling to catalog senescence-dependent cis-regulatory variation between the species at thousands of genes. We then tested for correlation between these expression changes and interspecies sequence variants in the binding sites of transcription factors. Among the emergent candidate senescence regulators, we chose a little-studied cell cycle factor, USF2, for molecular validation. In acute irradiation experiments, cells lacking USF2 had compromised DNA damage repair and response. Longer-term senescent cultures without USF2 mounted an exaggerated senescence regulatory program--shutting down cell cycle and DNA repair pathways, and turning up cytokine expression, more avidly than wild-type. We interpret these findings under a model of pro-repair, anti-senescence regulatory function by USF2. Our study affords new insights into the mechanisms by which cells commit to senescence, and serves as a validated proof of concept for natural variation-based regulator screens.

genomics↗

bioRxiv2021

The evolution of widespread recombination suppression on the Dwarf Hamster (Phodopus) X chromosome

The mammalian X chromosome shows strong conservation among distantly related species, limiting insights into the distinct selective processes that have shaped sex chromosome evolution. We constructed a chromosome-scale de novo genome assembly for the Siberian dwarf hamster (Phodopus sungorus), a species reported to show extensive recombination suppression across an entire arm of the X chromosome. Combining a physical genome assembly based on shotgun and long-range proximity ligation sequencing with a dense genetic map, we detected widespread suppression of female recombination across [~]65% of the Phodopus X chromosome. This region of suppressed recombination likely corresponds to the Xp arm, which has previously been shown to be highly heterochromatic. Using additional sequencing data from two closely-related species (P. campbelli and P. roborovskii), we show that recombination suppression on Xp appears to be independent of major structural rearrangements. The suppressed Xp arm was enriched for several transposable element families and de-enriched for genes primarily expressed in the placenta, but otherwise showed similar gene densities, expression patterns, and rates of molecular evolution when compared to the recombinant Xq arm. Phodopus Xp gene content and order was also broadly conserved relative to the more distantly related rat X chromosome. Collectively, these data suggest that widespread suppression of recombination has likely evolved through the transient induction of facultative heterochromatin on the Phodopus Xp arm without major changes in chromosome structure or genetic content. Thus, dramatic changes in the recombination landscape have so far had relatively subtle influences on overall patterns of X-linked molecular evolution. Significance StatementSex chromosome evolution represents a dynamic process of genomic specialization that is thought to be dependent on evolution of recombination. Here we use genome sequencing and genetic mapping to show that one arm comprising the majority of the X chromosome in a species of dwarf hamster has largely lost the ability to recombine in males and females. Although these dramatic shifts in recombination frequencies might eventually lead to sex chromosome degeneration, loss of recombination on this arm is associated with relatively minor changes in chromosome structure and gene contents in this species. These results underscore the conservation of the X chromosome across mammals, and allow us to test predictions about how genetic recombination influences sex chromosome evolution.

genomics↗

bioRxiv2021

Polygenic sex determination produces modular sex polymorphism in an African cichlid fish

For many vertebrates, a single genetic locus initiates a cascade of developmental sex differences in the gonad and throughout the organism, resulting in adults with two, phenotypically distinct sexes. Species with polygenic sex determination (PSD) have multiple interacting sex determination alleles segregating within a single species, allowing for more than two genotypic sexes, and scenarios where sex genotype at a given locus can be decoupled from gonadal sex. Here we investigate the effects of PSD on secondary sexual characteristics in the cichlid fish Metriaclima mbenjii, where one female (W) and one male (Y) sex determination allele interact to produce siblings with four possible sex classes: ZZXX females, ZWXX females, ZWXY females, and ZZXY males. We find that PSD in M. mbenjii produces an interplay of sex-linkage and sex-limitation resulting in modular variation in morphological and behavioral traits. Further, the evolution or introgression of a novel sex determiner creates additional axes of phenotypic variation for varied traits, including genital morphology, craniofacial morphology, gastrointestinal morphology, and home tank behaviors. In contrast to single-locus sex determination, which broadly results in sexual dimorphism, polygenic sex determination can induce higher-order sexual polymorphism. The modularity of secondary sexual characteristics produced by PSD provides novel context for understanding the evolutionary causes and consequences of maintenance, gain, or loss of sex determination alleles in populations. Significance StatementSex differences in traits can occur when those traits are modified by genetic factors inherited on sex chromosomes. We investigated how sex differences emerge in a species with more than one set of sex chromosomes, measuring a variety of morphological, physiological, and behavioral traits. Rather than exhibiting sexual dimorphism associated with primary sex, the species has higher-order sexual polymorphism in secondary sexual characteristics, or more than two phenotypic sexes. Variation in secondary sexual characteristics is modular, involving the interplay of sex-linked and sex-limited traits. Our findings provide novel implications for how sex determination systems and whole-organism fitness traits co-evolve, including that significant creation or loss of variation in diverse traits can occur during transitions among sex chromosome systems.

evolutionary biology↗

bioRxiv2021

Genetic basis of body shape variation along the benthic-pelagic axis in cichlid fishes

Divergence along the benthic-pelagic axis is one of the most widespread and repeated patterns of morphological variation in fishes, producing body shape diversity associated with ecology and swimming mechanics. This ecological shift is also the first stage of the explosive adaptive radiation of cichlid fishes in the East African Rift Lakes. We use two hybrid crosses of cichlids (Metriaclima sp. x Aulonocara sp. and Labidochromis sp. x Labeotropheus sp., >975 animals total) along the benthic-pelagic ecomorphological axis to determine the genetic basis of body shape diversification. Using a series of both linear and geometric shape measurements, we identify 55 quantitative trait loci (QTL) that underlie various aspects of body shape variation associated with benthic-pelagic divergence. These QTL are spread throughout the genome, each explain 3.0-7.2% of phenotypic variation, and are largely modular. Further, QTL are distinct both between these two crosses of Lake Malawi cichlids and compared to previously identified QTL for body shape in fishes such as sticklebacks. We find that body shape is controlled by many genes of small effects. In all, we find that convergent benthic and pelagic body phenotypes commonly observed across fish clades are most likely due to distinct genetic and molecular mechanisms.

evolutionary biology↗

bioRxiv2020

X chromosome-dependent disruption of placental regulatory networks in hybrid dwarf hamsters

Embryonic development in mammals is highly sensitive to changes in gene expression within the placenta. The placenta is also highly enriched for genes showing parent-of-origin or imprinted expression, which is predicted to evolve rapidly in response to parental conflict. However, little is known about the evolution of placental gene expression, or if divergence of placental gene expression plays an important role in mammalian speciation. We used crosses between two species of dwarf hamsters (Phodopus sungorus and P. campbelli) to examine the genetic and regulatory underpinnings of severe placental overgrowth in their hybrids. Using quantitative genetic mapping and mitochondrial substitution lines, we show that overgrowth of hybrid placentas was primarily caused by genetic differences on the maternally inherited P. sungorus X chromosome. Mitochondrial interactions did not contribute to abnormal hybrid placental development, and there was only weak correspondence between placental disruption and embryonic growth. Genome-wide analyses of placental transcriptomes from the parental species and first and second-generation hybrids revealed a central group of co-expressed X-linked and autosomal genes that were highly enriched for maternally-biased expression. Expression of this gene network was strongly correlated with placental size and showed widespread misexpression dependent on epistatic interactions with X-linked hybrid incompatibilities. Collectively, our results indicate that the X chromosome is likely to play a prominent role in the evolution of placental gene expression and the accumulation of hybrid developmental barriers between mammalian species.

evolutionary biology↗

bioRxiv2019

Heterospecific aggression differs predominately by species, rather than sex, in Lake Malawi cichlid fish

Because of their striking diversity, Lake Malawi cichlid fish have been well studied for male aggression, particularly among dominant males of closely related sister species within the framework of mate-choice and speciation. However, aggression in females has been largely ignored, and variation in aggressive behaviors between more distantly-related taxa is not well understood despite its potential impact in a complex community structure. To better understand variation in patterns of aggression between species, we presented males and females from five species of Lake Malawi cichlid with a non-predator intruder and recorded all movement and aggressive acts. Additionally, we measured excreted cortisol levels the day after the intruder assay to evaluate one physiological aspect of stress response. We identified species-specific patterns in both specific aggressive acts, and overall level of aggression. Additionally, we found that sexual dimorphism in aggressive acts varies by species and act, where the species with the most aggressive males also has aggressive females. Additionally, cortisol levels vary by taxa, and are associated with restless behavior in the intruder assay, but not levels of aggression. These findings have bearing on understanding sex differences in aggression and their impact on community structure in this important model of rapid evolution.

animal behavior and cognition↗

bioRxiv2019

Microhabitat predicts species differences in exploratory behavior in Lake Malawi cichlids

Encountering and adaptively responding to unfamiliar or novel stimuli is a fundamental challenge facing animals and is linked to fitness. Behavioral responses to novel stimuli, or exploratory behavior, can differ strongly between closely related species; however, the ecological and evolutionary factors underlying these differences are not well understood, in part because most comparative investigations have focused on only two species. In this study, we investigate exploratory behavior across 23 species in a previously untested vertebrate system, Lake Malawi cichlid fishes, which comprises hundreds of phenotypically diverse species that have diverged in the past one million years. We investigate behavioral variation across species, across microhabitats, and across environmental contexts. We find strong species differences in behavior that are associated with microhabitat, demonstrate that intermediate microhabitats are associated with higher levels of exploratory behavior, show that patterns of behavioral covariation across contexts are characteristic of modular complex traits, and contrast Malawi cichlid data with behavioral data from selectively bred high-and low-exploratory zebrafish. Taken together, our results tie ecology to species differences in behavior, and highlight Lake Malawi cichlids as a powerful system for understanding the evolution, ecology, and biology of natural behavioral variation. HighlightsO_LIMalawi cichlids exhibit high phenotypic variance in exploratory behaviors C_LIO_LISpecies differences in exploratory behavior are explained by microhabitat C_LIO_LIRock-dwelling species exhibit strong edge preferences across assays C_LIO_LIIntermediate habitats are associated with "high exploratory" open field behavior C_LIO_LIPatterns of behavioral covariance across contexts are modular in Malawi cichlids C_LI

animal behavior and cognition↗

bioRxiv2018

Chromosome-scale assemblies reveal the structural evolution of African cichlid genomes

BackgroundAfrican cichlid fishes are well known for their rapid radiations and are a model system for studying evolutionary processes. Here we compare multiple, high-quality, chromosome-scale genome assemblies to understand the genetic mechanisms underlying cichlid diversification and study how genome structure evolves in rapidly radiating lineages.\n\nResultsWe re-anchored our recent assembly of the Nile tilapia (Oreochromis niloticus) genome using a new high-density genetic map. We developed a new de novo genome assembly of the Lake Malawi cichlid, Metriaclima zebra, using high-coverage PacBio sequencing, and anchored contigs to linkage groups (LGs) using four different genetic maps. These new anchored assemblies allow the first chromosome-scale comparisons of African cichlid genomes.\n\nLarge intra-chromosomal structural differences (~2-28Mbp) among species are common, while inter-chromosomal differences are rare (< 10Mbp total). Placement of the centromeres within chromosome-scale assemblies identifies large structural differences that explain many of the karyotype differences among species. Structural differences are also associated with unique patterns of recombination on sex chromosomes. Structural differences on LG9, LG11 and LG20 are associated with reductions in recombination, indicative of inversions between the rock- and sand-dwelling clades of Lake Malawi cichlids. M. zebra has a larger number of recent transposable element (TE) insertions compared to O. niloticus, suggesting that several TE families have a higher rate of insertion in the haplochromine cichlid lineage.\n\nConclusionThis study identifies novel structural variation among East African cichlid genomes and provides a new set of genomic resources to support research on the mechanisms driving cichlid adaptation and speciation.

genomics↗