Biology subjects

Nachman, M. W.

Publications and source records attributed to Nachman, M. W..

13 recordsLinked to original sources

bioRxiv2026

Transposable element variation inferred from long-read sequences in wild house mice from temperate and tropical environments

Transposable elements (TEs) constitute a large fraction of mammalian genomes yet their contribution to variation among individuals within natural populations remains largely unexplored. While most TE insertions are deleterious, some may be beneficial and contribute to adaptation. We characterized TE variation and assessed its potential adaptive role using long-read whole-genome sequencing of wild-caught house mice (Mus musculus domesticus) sampled from two populations inhabiting contrasting temperate and tropical environments and differing in morphology, physiology, and behavior. We sequenced 10 mice from each population and created highly contiguous de-novo genome assemblies for each individual, allowing us to identify TEs that are not present in the mouse reference genome and to characterize individual variation. By performing manual TE curation, we identified 506 non-redundant TE consensus sequences among all mice. On average, each wild mouse genome contained 1.47 million TE insertions, ~4% of which were polymorphic among individuals. A small fraction of these polymorphic TE insertions were present in high frequency in just one of the populations, consistent with positive natural selection. Using liver RNA-seq in natural populations and in laboratory crosses, we studied gene expression at genes adjacent to polymorphic TEs. This identified a small set of TEs that are associated with the expression of nearby genes in a population-specific manner, nearly all of which showed independent signatures of positive selection. Together, these results provide the first detailed assessment of TE variation in natural populations of house mice and identify a small set of TE insertions that likely contribute to environmental adaptation.

evolutionary biology↗

bioRxiv2026

A maternal effect shapes early-life adaptive body size variation in house mice

Almost all phenotypic variation is mediated by a combination of genetic and environmental effects. Importantly, the balance of these effects can fluctuate over an organisms lifespan, with the maternal environment being particularly important during early life, especially in mammals. Using house mice as a model, we combine behavioral, molecular, and quantitative genetic approaches to understand how genetic and maternal variation together shape phenotypic divergence in a classic example of morphological adaptation. Temperate house mice are larger than tropical house mice, conforming to Bergmanns rule. We find that cross-fostering leads to pronounced weight restriction in cold-adapted, large-bodied mice, revealing an important effect of maternal environment. We then describe the molecular underpinnings of genetic and maternal influences on weight by identifying both the genetically- and maternally-controlled differences in gene expression in liver, a key tissue regulating growth. Maternally plastic expression variation is largely controlled in trans-, while stable, genetic variation is mediated in cis-. Additionally, we link maternally-controlled expression variation in growth-restricted mice to known nutrient deficiency signaling pathways. Finally, we identify candidate loci underlying the genetic basis of adaptive body size divergence from a combination of selection scans in wild populations and cis-regulated genes that overlap QTL identified in a mapping panel of temperate and tropical mice. Collectively, these results provide insight into how genetic and environmental forces influence adaptive phenotypic divergence in the context of a critical developmental window. SIGNIFICANCEAdaptive phenotypes arise from both genetic and environmental influences, yet their unique contributions are rarely resolved within the same natural system. Using locally-adapted house mice that conform to Bergmanns rule, we experimentally disentangled the genetic and plastic determinants of adaptive body size, focusing on the maternal environment. A maternal effect explains the majority of body weight variation during nursing and is linked to transcriptional changes in nutrient sensing pathways. By separating maternally- and genetically-determined transcriptional variation, we revealed distinct regulatory architectures for plastic and stable expression and identified candidate genes underlying adaptive body size divergence. This work offers broad insight into adaptive evolution and specific details on the mechanistic basis of one of the most widespread ecogeographic patterns in nature.

evolutionary biology↗

bioRxiv2025

Regionally specific and highly pleiotropic loci together mediate skeletal evolution in tropical and temperate house mice

When organisms are exposed to new environments, they often evolve a suite of adaptive phenotypic changes. Understanding the genetic basis of these changes gives us insight into the factors that constrain and facilitate the process of adaptation. Here we use quantitative trait locus (QTL) mapping in wild-derived house mice from temperate and tropical environments to describe the genetic architecture of adaptive skeletal evolution. This study provides a unique view into the evolution of discordant phenotypic changes within the interconnected skeletal system, since tropical and temperate mice have evolved under the opposing forces of Allens and Bergmanns rules (shorter extremities, but larger body size in cold climates). We generated an F3 mapping population of 449 mice and measured a variety of cranial and post-cranial skeletal traits. First, we discovered that temperate and tropical house mice have undergone extensive skeletal divergence in accordance with Allens and Bergmanns rules. Warm-adapted mice have longer limbs, longer pelvic girdles, longer and narrower skulls, but smaller overall body size. Second, we identified 83 QTL across 13 traits and found that the genetic basis of skeletal divergence involved mainly additive, small-effect loci distributed across the genome. While most QTL influenced only one or two traits, we also identified several highly pleiotropic QTL that influenced multiple traits across the skeletal system, often antagonistically to the evolved difference. Such pleiotropic loci may constrain adaptation. Lastly, we found that QTL for overall skeletal variation were enriched for signatures of selection in wild house mouse populations, providing evidence that skeletal variation in this system is indeed driven by adaptive evolution. Article SummaryThe incredible diversity of the vertebrate skeleton offers an opportunity to explore the genetic architecture of phenotypic variation, which is essential to understanding the process of evolution. We characterize the genetic basis of morphological evolution using QTL mapping in house mice adapted to differing climates. Skeletal divergence is widespread in these mice and reflects temperature adaptation. This divergence is mediated by small-effect loci scattered across the genome, as well as several highly-pleiotropic loci. Interestingly, pleiotropic loci often influence phenotypes in the opposite direction from the evolved change, perhaps constraining the process of adaptation. This work demonstrates how complex morphological changes can evolve within an interconnected system, such as the skeleton, under functional, developmental, and selective constraints.

evolutionary biology↗

bioRxiv2023

Arctos: Community-driven innovations for managing biodiversity and cultural collections

Museum collections house millions of objects and associated data records that document biological and cultural diversity. In recent decades, digitization efforts have greatly increased accessibility to these data, thereby revolutionizing interdisciplinary studies in evolutionary biology, biogeography, epidemiology, cultural change, and human-mediated environmental impacts. Curators and collection managers can make museum data as accessible as possible to scientists and learners by using a collection management system. However, selecting a system can be a challenging task. Here, we describe Arctos, a community solution for managing and accessing collections data for research and education. Specific goals are to: (1) Describe the core elements of Arctos for a broad audience with respect to the biodiversity informatics principles that enable high quality research; (2) Highlight the unique aspects of Arctos; (3) Illustrate Arctos as a model for supporting and enhancing the Digital Extended Specimen; and (4) Emphasize the role of the Arctos community for improving data discovery and enabling cross-disciplinary, integrative studies within a sustainable governance model. In addition to detailing Arctos as both a community of museum professionals and a collection database platform, we discuss how Arctos achieves its richly annotated data by creating a web of knowledge with deep connections between catalog records and derived or associated data. We also highlight the value of Arctos as an educational resource. Finally, we present a financial model of fiscal sponsorship by a non-profit organization, implemented in 2022, to ensure the long-term success and sustainability of Arctos. We attribute Arctos longevity of nearly three decades to its core development principles of standardization, flexibility, interdisciplinarity, and connectivity within a nimble development model for addressing novel needs and information types in response to changing technology, workflows, ethical considerations, and regulations.

bioinformatics↗

bioRxiv2023

Across two continents: the genomic basis of environmental adaptation in house mice (Mus musculus domesticus) from the Americas

AO_SCPLOWBSTRACTC_SCPLOWParallel clines across environmental gradients can be strong evidence of adaptation. House mice (Mus musculus domesticus) were introduced to the Americas by European colonizers and are now widely distributed from Tierra del Fuego to Alaska. Multiple aspects of climate, such as temperature, vary predictably across latitude in the Americas. Past studies of North American populations across latitudinal gradients provided evidence of environmental adaptation in traits related to body size, metabolism, and behavior and identified candidate genes using selection scans. Here, we investigate genomic signals of environmental adaptation on a second continent, South America, and ask whether there is evidence of parallel adaptation across multiple latitudinal transects in the Americas. We first identified loci across the genome showing signatures of selection related to climatic variation in mice sampled across a latitudinal transect in South America, accounting for neutral population structure. Consistent with previous results, most candidate SNPs were in regulatory regions. Genes containing the most extreme outliers relate to traits such as body weight or size, metabolism, immunity, fat, and development or function of the eye as well as traits associated with the cardiovascular and renal systems. We then combined these results with published results from two transects in North America. While most candidate genes were unique to individual transects, we found significant overlap among candidate genes identified independently in the three transects, providing strong evidence of parallel adaptation and identifying genes that likely underlie recent environmental adaptation in house mice across North and South America. Author summarySince their arrival with European colonizers, house mice have successfully spread throughout the Americas. There is strong evidence that populations in North America have adapted in that time, including parallel evolution of phenotypes across latitude (e.g., body size, behavior) as well as the identification of genes that show signals of selection. Here, we investigate the genetics of environmental adaptation in South America. We find that populations in South America evolve independently of populations in North America. We identify candidate genes for environmental adaptation with links to traits like body size, metabolism, immunity, eye function, and the cardiovascular and renal systems. We then bring together data from three transects across two continents to determine if environmental adaptation is predictable, with parallel genetic changes in response to shared conditions. We find that most evidence of environmental adaptation lies in regulatory regions and that, while most candidate genes are unique to individual transects, many are shared, providing significant evidence of parallel adaptation. We identify a core set of candidate genes independently identified in all three transects that likely contribute to environmental adaptation in the Americas. These results highlight the value of studying wild populations of this genetic model system.

evolutionary biology↗

bioRxiv2023

Remarkably high repeat content in the genomes of sparrows: the importance of genome assembly completeness for transposable element discovery.

Transposable elements (TE) play critical roles in shaping genome evolution. However, the highly repetitive sequence content of TEs is a major source of assembly gaps. This makes it difficult to decipher the impact of these elements on the dynamics of genome evolution. The increased capacity of long-read sequencing technologies to span highly repetitive regions of the genome should provide novel insights into patterns of TE diversity. Here we report the generation of highly contiguous reference genomes using PacBio long read and Omni-C technologies for three species of sparrows in the family Passerellidae. To assess the influence of sequencing technology on TE annotation, we compared these assemblies to three chromosome-level sparrow assemblies recently generated by the Vertebrate Genomes Project and nine other sparrow species generated using a variety of short- and long-read technologies. All long-read based assemblies were longer in length (range: 1.12-1.41 Gb) than short-read assemblies (0.91-1.08 Gb). Assembly length was strongly correlated with the amount of repeat content, with longer genomes showing much higher levels of repeat content than typically reported for the avian order Passeriformes. Repeat content for the Bells sparrow (31.2% of genome) was the highest level reported to date for a songbird genome assembly and was more in line with woodpecker (order Piciformes) genomes. CR1 LINE elements retained from an expansion that occurred 25-30 million years ago were the most abundant TEs in the song sparrow genome. Although the other five sparrow species also exhibit evidence for a spike in CR1 LINE activity at 25-30 million years ago, LTR elements stemming from more recent expansions were the most abundant elements in these species. LTRs were uniquely abundant in the Bells sparrow genome deriving from two recent peaks of activity. Higher levels of repeat content (79.2-93.7%) were found on the W chromosome relative to the Z (20.7-26.5) or autosomes (16.1-30.9%). These patterns support a dynamic model of transposable element expansion and contraction underpinning the seemingly constrained and small sized genomes of birds. Our work highlights how the resolution of difficult-to-assemble regions of the genome with new sequencing technologies promises to transform our understanding of avian genome evolution.

genomics↗

bioRxiv2023

Tissue-specific and cis-regulatory changes underlie parallel, adaptive gene expression evolution in house mice

Changes in gene regulation have long been appreciated as a driving force of adaptive evolution, however the relative contributions of cis- and trans-acting changes to gene regulation over short evolutionary timescales remain unclear. Instances of recent, parallel phenotypic evolution provide an opportunity to assess whether parallel patterns are seen at the level of gene expression, and to assess the relative contribution of cis- and trans-changes to gene regulation in the early stages of divergence. Here, we studied gene expression in liver and brown adipose tissue in two wild-derived strains of house mice that independently adapted to cold, northern environments, and we compared them to a strain of house mice from a warm, southern environment. To investigate gene regulatory evolution, we studied expression in parents and allele-specific expression in F1 hybrids of crosses between warm-adapted and cold-adapted strains. First, we found that the different cold-adapted mice showed both unique and shared changes in expression, but that the proportion of shared changes (i.e. parallelism) was greater than expected by chance. Second, we discovered that expression evolution occurred largely at tissue-specific and cis-regulated genes, and that these genes were over-represented in parallel cases of evolution. Finally, we integrated the expression data with scans for selection in natural populations and found substantial parallelism in the two northern populations for genes under selection. Furthermore, selection outliers were associated with cis-regulated genes more than expected by chance; cis-regulated genes under selection influenced phenotypes such as body size, fat content, immune functioning, and skeletal morphology. These results demonstrate that parallel patterns of gene expression in mice that have independently adapted to cold environments are driven largely by tissue-specific and cis-regulatory changes, providing insight into the mechanisms of adaptive gene regulatory evolution at the earliest stages of divergence. Author summaryThe parallel movement of organisms into novel environments provides an opportunity to understand the molecular basis of adaptation and the repeatability of this process. Mutations affecting the expression of genes are known to underlie much of adaptive evolution. Such mutations can arise in cis-(near the gene of interest) or in trans-(at a distant locus), but the relative contribution of these different kinds of changes to adaptation is poorly understood, especially during very recent divergence. Here, we compared evolved gene expression differences between a warm-adapted house mouse strain and two different cold-adapted strains that have independently evolved similar phenotypic traits, such as increased body size and decreased extremity length during the last few hundred years. Using crosses between warm-adapted and cold-adapted mice, we found that mutations acting in a context specific manner (cis-regulatory and tissue-specific changes) predominate expression divergence and are more likely to be involved in parallel evolution. We used population level selection scans in wild animals to identify regions of the genome under selection and combined these findings with the gene expression data to identify candidate genes underlying adaptation to novel environments. Together, our work describes the gene regulatory dynamics of rapid environmental adaptation, and the repeatability of these patterns over multiple instances of adaptation.

evolutionary biology↗

bioRxiv2023

Alternative splicing and environmental adaptation in house mice

A major goal of evolutionary genetics is to understand the genetic and molecular mechanisms underlying adaptation. Previous work has established that changes in gene regulation may contribute to adaptive evolution, but most studies have focused on mRNA abundance and only a few studies have investigated the role of post-transcriptional processing. Here, we use a combination of exome sequences and short-read RNA-Seq data from wild house mice (Mus musculus domesticus) collected along a latitudinal transect in eastern North America to identify candidate genes for local adaptation through alternative splicing. First, we identified alternatively spliced transcripts that differ in frequency between mice from the northern-most and southern-most populations in this transect. We then identified the subset of these transcripts that exhibit clinal patterns of variation among all populations in the transect. Finally, we conducted association studies to identify cis-acting splicing quantitative trait loci (cis-sQTL), and we identified cis-sQTL that overlapped with previously ascertained targets of selection from genome scans. Together, these analyses identified a small set of alternatively spliced transcripts that may underlie environmental adaptation in house mice. Many of these genes have known phenotypes associated with body size, a trait that varies clinally in these populations. We observed no overlap between these genes and genes previously identified by changes in transcript level, indicating that alternative splicing and changes in mRNA abundance may provide separate molecular mechanisms of adaptation.

evolutionary biology↗

bioRxiv2022

Genomic data suggest parallel dental vestigialization within the xenarthran radiation

AO_SCPLOWBSTRACTC_SCPLOWThe recent influx of genomic data has provided greater insights into the molecular basis for regressive evolution, or vestigialization, through gene loss and pseudogenization. As such, the analysis of gene degradation patterns has the potential to provide insights into the evolutionary history of regressed anatomical traits. We specifically applied these principles to the xenarthran radiation (anteaters, sloths, armadillos), which is characterized by taxa with a gradation in regressed dental phenotypes. Whether the pattern among extant xenarthrans is due to an ancient and gradual decay of dental morphology or occurred repeatedly in parallel is unknown. We tested these competing hypotheses by examining 11 core dental genes in most living species of Xenarthra, characterizing shared inactivating mutations and patterns of relaxed selection during their radiation. Here we report evidence of independent and distinct events of dental gene loss in the major xenarthran subclades. First, we found strong evidence of complete enamel loss in the common ancestor of sloths and anteaters, suggested by the inactivation of five enamel-associated genes (AMELX, AMTN, MMP20, ENAM, ACP4). Next, whereas dental regression appears to have halted in sloths, presumably a critical event that ultimately permitted adaptation to an herbivorous lifestyle, anteaters continued losing genes on the path towards complete tooth loss. Echoes of this event are recorded in the genomes of all living anteaters, being marked by a 2-bp deletion in a gene critical for dentinogenesis (DSPP) and a putative shared 1-bp insertion in a gene linked to tooth retention (ODAPH). By contrast, in the two major armadillo clades, genes pertaining to the dento-gingival junction and amelogenesis appear to have been independently inactivated prior to losing all or some enamel. These genomic data provide evidence for multiple pathways and rates of anatomical regression, and underscore the utility of using pseudogenes to reconstruct evolutionary history when fossils are sparse.

evolutionary biology↗

bioRxiv2022

Environmentally robust cis-regulatory changes underlie rapid climatic adaptation

Changes in gene expression are proposed to play a major role in adaptive evolution. While it is known that gene expression is highly sensitive to the environment, very few studies have determined the influence of genetic and environmental effects on adaptive gene regulation in natural populations. Here, we utilize allele-specific expression to characterize cis and trans gene regulatory divergence in temperate and tropical house mice in two metabolic tissues under two thermal conditions. First, we show that gene expression divergence is pervasive between populations and across thermal conditions, with roughly 5-10% of genes exhibiting genotype-by-environment interactions. Second, we found that most expression divergence was due to cis-regulatory changes that were stable across temperatures. In contrast, patterns of expression plasticity were largely attributable to trans-effects, which showed greater sensitivity to temperature. Nonetheless, we discovered a small subset of temperature-dependent cis-regulatory changes, thereby identifying loci underlying expression plasticity. Finally, we performed scans for selection in wild house mice to identify genomic signatures of rapid adaptation. Genomic outliers were enriched in genes with evidence for cis-regulatory divergence. Notably, these genes were associated with phenotypes that affected body weight and metabolism, suggesting that cis-regulatory changes are a possible mechanism for adaptive body size evolution between populations. Our results show that gene expression plasticity, largely controlled in trans, may facilitate the colonization of new environments, but that evolved changes in gene expression are largely controlled in cis, illustrating the genetic and non-genetic mechanisms underlying the establishment of populations in new environments. Significance StatementGene expression variation is shaped by both genetic and environmental effects, yet these two factors are rarely considered together in the context of adaptive evolution. We studied environmental influences on gene regulatory evolution in temperate and tropical house mice in cold and warm laboratory environments. We discovered that genetic effects in the form of cis-regulatory divergence were pervasive and largely insensitive to the environment. Many of these genetic effects are under selection and are associated with genes that affect body size, suggesting cis-regulatory changes as a possible mechanism for adaptive body size evolution. We also discovered many trans-effects controlling expression plasticity, demonstrating the importance of both genetic and non-genetic changes associated with adaptation over short timescales (a few hundred generations).

evolutionary biology↗

bioRxiv2021

Convergent patterns of gene expression and protein evolution associated with adaptation to desert environments in rodents

Desert specialization has arisen multiple times across rodents and is often associated with a suite of convergent phenotypes, including modification of the kidneys to mitigate water loss. However, the extent to which phenotypic convergence in desert rodents is mirrored at the molecular level is unknown. Here, we sequenced kidney mRNA and assembled transcriptomes for three pairs of rodent species to search for convergence in gene expression and amino acid sequence associated with adaptation to deserts. We conducted phylogenetically-independent comparisons between a desert specialist and a non-desert relative in three families representing [~]70 million years of evolution. Overall, patterns of gene expression faithfully recapitulated the phylogeny of these six taxa. However, we found that 8.6% of all genes showed convergent patterns of expression evolution between desert and non-desert taxa, a proportion that is much higher than expected by chance. In addition to these convergent changes, we observed many species-pair specific changes in gene expression indicating that different instances of adaptation to deserts include a combination of unique and shared changes. Patterns of protein evolution revealed a small number of genes showing evidence of positive selection, the majority of which did not show convergent changes in gene expression. Overall, our results suggest convergent changes in gene regulation play a primary role in the complex trait of desert adaptation in rodents.

evolutionary biology↗

bioRxiv2021

The contribution of genetic and environmental effects to Bergmanns rule and Allens rule in house mice

Distinguishing between genetic, environmental, and genotype-by-environment effects is central to understanding geographic variation in phenotypic clines. Two of the best-documented phenotypic clines are Bergmanns rule and Allens rule, which describe larger body sizes and shortened extremities in colder climates, respectively. Although numerous studies have found inter- and intraspecific evidence for both ecogeographic patterns, we still have a poor understanding of the extent to which these patterns are driven by genetics, environment, or both. Here, we measured the genetic and environmental contributions to Bergmanns rule and Allens rule across introduced populations of house mice (Mus musculus domesticus) in the Americas. First, we documented clines for body mass, tail length, and ear length in natural populations, and found that these conform to both Bergmanns rule and Allens rule. We then raised descendants of wild-caught mice in the lab and showed that these differences persisted in a common environment and are heritable, indicating that they have a genetic basis. Finally, using a full-sib design, we reared mice under warm and cold conditions. We found very little plasticity associated with body size, suggesting that Bergmanns rule has been shaped by strong directional selection in house mice. However, extremities showed considerable plasticity, as both tails and ears grew shorter in cold environments. These results indicate that adaptive phenotypic plasticity as well as genetic changes underlie major patterns of clinal variation in house mice and likely facilitated their rapid expansion into new environments across the Americas.

evolutionary biology↗

bioRxiv2020

Plasticity in gene expression facilitates invasion of the desert environment in house mice

Understanding how organisms adapt to new environments is a key problem in evolution, yet it remains unclear whether phenotypic plasticity generally facilitates or hinders this process. Here we studied the evolved and plastic responses to water stress in lab-born descendants of wild house mice (Mus musculus domesticus) collected from desert and non-desert environments. Using a full sib design, we measured organismal phenotypes and gene expression under normal (hydrated) and water stressed (dehydrated) conditions. After many generations in the lab, mice from the desert consumed significantly less water than mice from other localities, indicating that this difference has a genetic basis. Under water stress, desert mice lost less weight than non-desert mice, and desert mice exhibited differences in blood chemistry related to osmoregulatory function. Gene expression in the kidney revealed evolved differences between mice from different environments as well as plastic responses between hydrated and dehydrated mice. Desert mice showed reduced gene expression plasticity under water stress compared to non-desert mice. Importantly, the non-desert mice generally showed shifts towards desert-like expression under water stress, consistent with adaptive plasticity. Finally, patterns of gene expression identified several candidate genes for adaptation to the desert, including Aqp1 and Apoe. These findings provide evidence for local adaptation in a recently introduced species and suggest that adaptive plasticity may have facilitated the colonization of the desert environment.

evolutionary biology↗