Biology subjects

MacManes, M. D.

Publications and source records attributed to MacManes, M. D..

17 recordsLinked to original sources

bioRxiv2024

Impacts of dietary fat on multi tissue gene expression in the desert-adapted cactus mouse

Understanding the relationship between dietary fat and physiological responses is crucial in species adapted to arid environments where water scarcity is common. In this study, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract, and hypothalamus) and 19 phenotypic measurements, investigating the effects of dietary fat in the desert-adapted cactus mouse (Peromyscus eremicus). We show impacts on immune function, circadian gene regulation, and mitochondrial function for mice fed a lower-fat diet compared to mice fed a higher-fat diet. In arid environments with severe water scarcity, even subtle changes in organismal health and water balance can affect physical performance, potentially impacting survival and reproductive success. The study sheds light on the complex interplay between diet, physiological processes, and environmental adaptation, providing valuable insights into the multifaceted impacts of dietary choices on organismal well-being and adaptation strategies in arid habitats.

genomics↗

bioRxiv2023

When the tap runs dry: The physiological effects of acute experimental dehydration in Peromyscus eremicus

Desert organisms have evolved physiological, biochemical, and genomic mechanisms to survive the extreme aridity of desert environments. Studying desert-adapted species provides a unique opportunity to investigate the survival strategies employed by organisms in some of the harshest habitats on Earth. Two of the primary challenges faced in desert environments are maintaining water balance and thermoregulation. We collected data in a simulated desert environment and a captive colony of cactus mice (Peromyscus eremicus) and used lab-based experiments with real time physiological measurements to characterize the response to water-deprivation. Mice without access to water had significantly lower energy expenditures and in turn, reduced water loss compared to mice with access to water after the first 24 hours of the experiment. Additionally, we observed significant weight loss likely related to dehydration-associated anorexia a response to limit fluid loss by reducing waste and the solute load as well as allowing water reabsorption from the kidneys and gastrointestinal tract. Finally, we observed body temperature correlated with sex, with males without access to water maintaining body temperature when compared to hydrated males while body temperature decreased for females without access to water compared to hydrated, suggesting daily torpor in females.

physiology↗

bioRxiv2023

Genetic basis of aposematic coloration in a mimetic radiation of poison frogs

The evolution of mimicry in a single species or population has rippling inter and intraspecific effects across ecological communities, providing a fascinating mechanism of phenotypic diversification. In this study we present the first identification of genes underlying Mullerian mimicry in a vertebrate, the Peruvian mimic poison frog, Ranitomeya imitator. We sequenced 124 R. imitator exomes and discovered loci with both strong divergence between different mimetic morphs and phenotypic associations within an intraspecific admixture zone, implicating mc1r, asip, bsn, retsat, and krt8.2 in the evolution of mimetic color phenotypes. We confirmed these associations for most candidate genes through linkage mapping in a lab-reared pedigree. We also sequenced transcriptomes from the model species, allowing tests for introgression and revealing that the mimetic resemblance between R. imitator and the models evolved independently. Selection analyses of the candidate genes show that the mimicry phenotypes likely have evolved through selective sweeps acting on polygenic variation. Our results suggest that the evolutionary origins and molecular mechanisms underlying mimicry phenotypes in vertebrates may be radically different from those previously documented in invertebrates such as the iconic Heliconius butterfly mimicry complex. One Sentence SummaryMullerian mimicry evolved through independent selective sweeps on color and pattern loci in the mimic poison frog.

evolutionary biology↗

bioRxiv2022

High total water loss driven by low-fat diet in desert-adapted mice

Availability of food resources is an important driver of survival. Animals must either relocate or adapt to persist in environments where critical resource abundance is changing. An optimal diet balances energy gain, water regulation, and nutrition. We used flow-through respirometry to characterize metabolic phenotypes of the desert-adapted cactus mouse (Peromyscus eremicus) under diurnally variable environmental conditions that mimic the environment of the Sonoran Desert. We treated mice with two different energetically equivalent diets, a standard diet and a low-fat diet, and measured energy expenditure, water loss rate, respiratory quotient, weight, and electrolyte levels. Mice fed the low-fat diet lost significantly more water than those on the standard diet. Our results suggest that cactus mice may have limited capacity to tolerate water deprivation if optimal foods become less abundant. Given that climate change is predicted to modify the distribution of food items, understanding these links may have important implications for long-term population viability for desert and non-desert adapted animals alike.

physiology↗

bioRxiv2021

Prolactin and prolactin receptor expression in the HPG axis and crop sac during parental care in both sexes of a biparental bird (Columba livia)

During breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies parental behaviors and related physiological changes across many vertebrates, including birds and mammals. While circulating prolactin levels often fluctuate across breeding, less is known about how relevant target tissues vary in their prolactin responsiveness via prolactin receptor (PRLR) expression. Recent studies have also investigated prolactin (PRL) gene expression outside of the pituitary (i.e., extra-pituitary PRL), but how PRL gene expression varies during parental care in non-pituitary tissue (e.g., hypothalamus, gonads) remains largely unknown. Further, it is unclear if and how tissue-specific PRL and PRLR vary between the sexes during biparental care. To address this, we measured PRL and PRLR gene expression in tissues relevant to parental care, the endocrine reproductive hypothalamic-pituitary-gonadal (HPG) axis and the crop (a tissue with a similar function as the mammalian mammary gland), across various reproductive stages in both sexes of a biparental bird, the rock dove (Columba livia). We also assessed how these genes responded to changes in offspring presence by adding chicks mid-incubation, simulating an early hatch when prolactin levels were still moderately low. We found that pituitary PRL expression showed similar increases as plasma prolactin levels, and detected extra-pituitary PRL in the hypothalamus, gonads and crop. Hypothalamic and gonadal PRLR expression also changed as birds began incubation. Crop PRLR expression correlated with plasma prolactin, peaking when chicks hatched. In response to replacing eggs with a novel chick mid-incubation, hypothalamic and gonadal PRL and PRLR gene expression differed significantly compared to mid-incubation controls, even when plasma prolactin levels did not differ. We also found sex differences in PRL and PRLR that suggest gene expression may allow males to compensate for lower levels in prolactin by upregulating PRLR in all tissues. Overall, this study advances our understanding of how tissue-specific changes in responsiveness to parental hormones may differ across key reproductive transitions, in response to offspring cues, and between the sexes.

animal behavior and cognition↗

bioRxiv2021

Chromosome size affects sequence divergence between species through the interplay of recombination and selection

The structure of the genome shapes the distribution of genetic diversity and sequence divergence. To investigate how the relationship between chromosome size and recombination rate affects sequence divergence between species, we combined empirical analyses and evolutionary simulations. We estimated pairwise sequence divergence among 15 species from three different Mammalian clades - Peromyscus rodents, Mus mice, and great apes - from chromosome-level genome assemblies. We found a strong significant negative correlation between chromosome size and sequence divergence in all species comparisons within the Peromyscus and great apes clades, but not the Mus clade, suggesting that the dramatic chromosomal rearrangements among Mus species may have masked the ancestral genomic landscape of divergence in many comparisons. Our evolutionary simulations showed that the main factor determining differences in divergence among chromosomes of different size is the interplay of recombination rate and selection, with greater variation in larger populations than in smaller ones. In ancestral populations, shorter chromosomes harbor greater nucleotide diversity. As ancestral populations diverge, diversity present at the onset of the split contributes to greater sequence divergence in shorter chromosomes among daughter species. The combination of empirical data and evolutionary simulations revealed that chromosomal rearrangements, demography, and divergence times may also affect the relationship between chromosome size and divergence, and deepen our understanding of the role of genome structure on the evolution of species divergence.

evolutionary biology↗

bioRxiv2020

Disentangling environmental drivers of circadian metabolism in desert-adapted mice

Metabolism is a complex phenotype shaped by natural environmental rhythms, as well as behavioral, morphological, and physiological adaptations. Although historically studied under constant environmental conditions, continuous metabolic phenotyping through environmental transitions now offers a window into the physiological responses of organisms to changing environments. Here, we use flow-through respirometry to compare metabolic responses of the desert-adapted cactus mouse (Peromyscus eremicus) between diurnally variable and constant environmental conditions. We contrast metabolic responses to circadian cycles in photoperiod, temperature, and humidity, against those recorded under constant hot-and-dry and constant cold-and-wet conditions. We found significant sexual dimorphism in metabolic responses, despite no measurable difference in body weight. Males seem to be more heat tolerant and females more cold tolerant. Under circadian environmental cycling, the ratio of CO2 produced to O2 consumed (the respiratory quotient or respiratory exchange ratio) reached greater than one, a pattern that strongly suggests that lipogenesis is contributing to the production of energy and endogenous water in this species. This hypothesis is consistent with the results of previous dehydration experiments in this species, which documented significant weight loss in response to dehydration, without other physiological impairment. Our results are also consistent with historical descriptions of circadian torpor in this species (torpid by day, active by night), but reject the hypothesis that this pattern is driven by food restriction or negative water balance, as both resources were available to animals throughout the experiments. SUMMARY STATEMENTContinuous metabolic phenotyping of desert-adapted cactus mice (Peromyscus eremicus) identifies significant metabolic differences between the sexes and circadian patterning consistent with lipogenesis and environmental entrainment.

physiology↗

bioRxiv2020

Signal, bias, and the role of transcriptome assembly quality in phylogenomic inference

The empirical details of whole transcriptome sequencing and assembly have been thoroughly evaluated, but few studies have addressed how user-defined aspects of the assembly process may influence performance in phylogenomic analyses. Errors in transcriptome assembly could affect ortholog prediction, alignment quality, and phylogenetic signal. Here we investigate the impacts of transcriptome assembly quality in phylogenomic studies by constructing phylogenomic data matrices from alternative transcriptome assemblies representing high-quality and intentionally low-quality assembly outcomes. We leveraged a well-resolved topology for craniates to apply a topological constraint to our analyses, providing a way to quantify phylogenetic signal. Craniates are amply represented in publicly available raw RNA-seq repositories, allowing us to control for transcriptome tissue type as well. By studying the performance of phylogenomic datasets derived from these alternative high- and low-quality inputs in a controlled experiment, we show that high-quality transcriptomes produce richer phylogenomic datasets with partitions that have lower alignment ambiguity, less compositional bias, and stronger phylogenetic signal than low-quality transcriptome assemblies. Our findings demonstrate the importance of transcriptome assembly in phylogenomic analyses and suggest that a portion of the uncertainty observed in phylogenomic studies could be alleviated at the assembly stage.

systems biology↗

bioRxiv2020

Multiple evolutionary pathways to achieve thermal adaptation in small mammals

Phenotypic plasticity enables an immediate response to changing conditions, but for most species, evolutionary change through adaptation will be more important for long-term survival. Warming climate and increasing desertification urges the identification of genes involved in heat-and dehydration-tolerance to better inform and target biodiversity conservation efforts. Comparisons among extant desert adapted species can highlight parallel or convergent patterns of genome evolution through the identification of shared signatures of selection. We generate chromosome-level genome assembly for the canyon mouse (Peromyscus crinitus) and test for signature of parallel evolution by comparing signatures of selective sweeps across population-level genomic resequencing data from another desert specialist deer mouse (P. eremicus) and a widely-distributed habitat generalist (P. maniculatus), that may locally adapted to arid conditions. We identify few shared candidate loci involved in desert adaptation and do not find support for a shared pattern of parallel evolution. Instead, we hypothesize divergent molecular mechanisms of desert adaptation among deer mice, potentially tied to species-specific historical demography, which may limit or enhance adaptation. We identify a number of candidate loci experiencing selective sweeps in the P. crinitus genome that are implicated in osmoregulation (Trypsin, Prostasin) and metabolic regulation (Kallikrein, eIF2-alpha kinase GCN2, APPL1/2), which may be important to accommodating hot and dry environmental conditions.

evolutionary biology↗

bioRxiv2019

Comparative and population genomics approaches reveal the basis of adaptation to deserts in a small rodent

Organisms that live in deserts offer the opportunity to investigate how species adapt to environmental conditions that are lethal to most plants and animals. In the hot deserts of North America, high temperatures and lack of water are conspicuous challenges for organisms living there. The cactus mouse (Peromyscus eremicus) displays several adaptations to these conditions, including low metabolic rate, heat tolerance, and the ability to maintain homeostasis under extreme dehydration. To investigate the genomic basis of desert adaptation in cactus mice, we built a chromosome-level genome assembly and resequenced 26 additional cactus mouse genomes from two locations in southern California (USA). Using these data, we integrated comparative, population, and functional genomic approaches. We identified 16 gene families exhibiting significant contractions or expansions in the cactus mouse compared to 17 other Myodontine rodent genomes, and found 232 sites across the genome associated with selective sweeps. Functional annotations of candidate gene families and selective sweeps revealed a pervasive signature of selection at genes involved in the synthesis and degradation of proteins, consistent with the evolution of cellular mechanisms to cope with protein denaturation caused by thermal and hyperosmotic stress. Other strong candidate genes included receptors for bitter taste, suggesting a dietary shift towards chemically defended desert plants and insects, and a growth factor involved in lipid metabolism, potentially involved in prevention of dehydration. Understanding how species adapted to the recent emergence of deserts in North America will provide an important foundation for predicting future evolutionary responses to increasing temperatures, droughts and desertification in the cactus mouse and other species.

evolutionary biology↗

bioRxiv2019

Stress-mediated convergence of splicing landscapes in male and female Rock Doves

BackgroundThe process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothlamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes.\n\nResultsThis study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, post submitting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3UTR end of transcripts than the 5UTR or coding regions.\n\nConclusionsOur results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stress-induced reproductive dysfunction.

genomics↗

bioRxiv2019

Differential gene expression and gene variants drive color and pattern development in divergent color morphs of a mimetic poison frog

A common goal in evolutionary biology is to discern the mechanisms that produce the astounding diversity of morphologies seen across the tree of life. Aposematic species, those with a conspicuous phenotype coupled with some form of defense, are excellent models to understand the link between vivid color pattern variations, the natural selection shaping it, and the underlying genetic mechanisms underpinning this variation. Mimicry systems in which multiple species share the same conspicuous phenotype can provide an even better model for understanding the mechanisms of color production in aposematic species, especially if comimics have divergent evolutionary histories. Here we investigate the genetic mechanisms by which vivid color and pattern are produced in a Mullerian mimicry complex of poison frogs. We did this by first assembling a high-quality de novo genome assembly for the mimic poison frog Ranitomeya imitator. This assembled genome is 6.8 Gbp in size, with a contig N50 of 300 Kbp and 93% of expected tetrapod genes. We then leveraged this genome to conduct gene expression analyses throughout development of four color morphs of R. imitator and two color morphs from both R. fantastica and R. variabilis which R. imitator mimics. We identified a large number of pigmentation and patterning genes that are differentially expressed throughout development, many of them related to melanocyte development, melanin synthesis, iridophore development, and guanine synthesis. In addition, we identify the pteridine synthesis pathway (including genes such as qdpr and xdh) as a key driver of the variation in color between morphs of these species. Finally, we hypothesize that genes in the keratin family are important for producing different structural colors within these frogs.

evolutionary biology↗

bioRxiv2019

White-nose syndrome restructures bat skin microbiomes

The skin microbiome is an essential line of host defense against pathogens, yet our understanding of microbial communities and how they change when hosts become infected is limited. We investigated skin microbial composition in three North American bat species (Myotis lucifugus, Eptesicus fuscus, and Perimyotis subflavus) that have been impacted by the infectious disease, white-nose syndrome, caused by an invasive fungal pathogen, Pseudogymnoascus destructans. We compared bacterial and fungal composition from 154 skin swab samples and 70 environmental samples using a targeted 16S rRNA and ITS amplicon approach. We found that for M. lucifugus, a species that experiences high mortality from white-nose syndrome, bacterial microbiome diversity was dramatically lower when P. destructans is present. Key bacterial families--including those potentially involved in pathogen defense--significantly differed in abundance in bats infected with P. destructans compared to uninfected bats. However, skin bacterial diversity was not lower in E. fuscus or P. subflavus when P. destructans was present, despite populations of the latter species declining sharply from white-nose syndrome. The fungal species present on bats substantially overlapped with the fungal taxa present in the environment at the site where the bat was sampled, but fungal community composition was unaffected by the presence of P. destructans for any of the three bat species. This species-specific alteration in bat skin bacterial microbiomes after pathogen invasion may suggest a mechanism for the severity of WNS in M. lucifugus, but not for other bat species impacted by white-nose syndrome.

microbiology↗

bioRxiv2018

Variation in pigmentation gene expression is associated with distinct aposematic color morphs in the poison frog, Dendrobates auratus

Color and pattern phenotypes have clear implications for survival and reproduction in many species. However, the mechanisms that produce this coloration are still poorly characterized, especially at the genomic level. Here we have taken a transcriptomics-based approach to elucidate the underlying genetic mechanisms affecting color and pattern in a highly polytypic poison frog. We sequenced RNA from the skin from four different color morphs during the final stage of metamorphosis and assembled a de novo transcriptome. We then investigated differential gene expression, with an emphasis on examining candidate color genes from other taxa. Overall, we found differential expression of a suite of genes that control melanogenesis, melanocyte differentiation, and melanocyte proliferation (e.g., tyrpl, lefl, leol, and mitf) as well as several differentially expressed genes involved in purine synthesis and iridophore development (e.g., arfgapl, arfgap2, airc, and gairt). Our results provide evidence that several gene networks known to affect color and pattern in vertebrates play a role in color and pattern variation in this species of poison frog.

evolutionary biology↗

bioRxiv2017

The Oyster River Protocol: A Multi Assembler and Kmer Approach For de novo Transcriptome Assembly

Characterizing transcriptomes in non-model organisms has resulted in a massive increase in our understanding of biological phenomena. This boon, largely made possible via high-throughput sequencing, means that studies of functional, evolutionary and population genomics are now being done by hundreds or even thousands of labs around the world. For many, these studies begin with a de novo transcriptome assembly, which is a technically complicated process involving several discrete steps. The Oyster River Protocol (ORP), described here, implements a standardized and benchmarked set of bioinformatic processes, resulting in an assembly with enhanced qualities over other standard assembly methods. Specifically, ORP produced assemblies have higher TransRate scores and mapping rates, which is largely a product of the fact that it leverages a multi-assembler and kmer assembly process, thereby bypassing the shortcomings of any one approach. These improvements are important, as previously unassembled transcripts are included in ORP assemblies, resulting in a significant enhancement of the power of downstream analysis. Further, as part of this study, we show that assembly quality is unrelated to taxonomy, nor is it related to the number of reads generated, above 30 million reads.\n\nCode AvailabilityThe version controlled open-source code is available at https://github.com/macmanes-lab/Oyster_River_Protocol. Instructions for software installation and use, and other details are available at http://oyster-river-protocol.rtfd.org/.

bioinformatics↗

bioRxiv2017

Sex-biased transcriptomic response of the reproductive axis to stress

Stress is a well-known cause of reproductive dysfunction in many species, including birds, rodents, and humans. However, little is known of the genomic basis for this dysfunction and how it may differ between the sexes. Using the classic reproductive model of the rock dove (Columba livia), we conducted the most in-depth investigation to date of how stress affects all gene transcription of a biological system essential for facilitating reproduction - the hypothalamic-pituitary-gonadal (HPG) axis. The HPG transcriptome responded to stress in both sexes, but females exhibited more differential expression than males, and these stress responsive genes were mostly unique to females. This result may be due to 1) fluctuations in the female endocrine environment to facilitate ovulation and follicle maturation, and 2) their evolutionary history. We offer a vital genomic foundation on which sex-specific reproductive dysfunction can be studied, as well as novel gene targets for genetic intervention and therapy investigations.

neuroscience↗

bioRxiv2017

Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury

Animal living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. Indeed, these animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert adapted rodent P. eremicus survives, we performed an experiment by which we subjected reproductively mature adults to profound acute dehydration, during which they lost on average 23% of their body weight. Animals react via a series of changes in the kidney, which include modulating expression of genes responsible for reducing the rate of transcription, and maintaining water and salt balance. Extracellular matrix turnover appears to be decreased, and apoptosis is limited. Serum Creatinine and other biomarkers of kidney injury are not elevated, which is different than the canonical human response, suggesting that transcriptional changes caused by acute dehydration effectively prohibit widespread kidney damage in the cactus mouse.

genomics↗