Biology subjects

Storz, J. F.

Publications and source records attributed to Storz, J. F..

At least 19 recordsLinked to original sources

bioRxiv2025

A Deep Dive into the Globin Superfamily of Sharks, Skates, and Rays: Contrasting patterns of gene loss and retention relative to bony vertebrates

The globin gene superfamily encodes oxygen-binding proteins that are present in all domains of life. Hemoglobins and myoglobins of jawed vertebrates are among the most well-studied proteins in the context of structure-function relationships and evolution after gene duplication. However, these studies have primarily focused on bony vertebrates, and research on globin gene evolution in cartilaginous fish has been limited by a lack of genomic resources. In this study, we leverage newly available cartilaginous fish genomes to investigate globin gene family evolution across skates, rays, sharks, and sawfish. We found that, when present, most globin genes are in a single copy, with androglobin, globin-Y, and myoglobin present in all cartilaginous fish, while the two globin-X genes were differentially retained between the Holocephali and sharks, skates, and rays. Neuroglobin appears to have been lost at the common ancestor of all cartilaginous fish. The - and {beta}-globin gene subfamilies underwent independent expansions in different lineages of cartilaginous fish. Most cartilaginous fish globins have conserved synteny with other jawed vertebrates except myoglobin. Additionally, NPRL3, which directly flanks the hemoglobin clusters of other jawed and jawless vertebrates and regulates hemoglobin gene expression, is on a separate chromosome from the hemoglobin clusters of cartilaginous fish. When we examined globin gene expression patterns across cartilaginous fish tissues and developmental stages, we found that most globins are expressed as expected compared to other jawed vertebrates. However, hemoglobin paralogs are more widely expressed in embryonic tissues compared to later-stage tissues in cases where many copies exist. Our results reveal similar and contrasting patterns of globin gene evolution between cartilaginous and bony vertebrates and shed light on the early stages of globin gene evolution in gnathostomes. Significance StatementThe evolution of the globin gene family in jawed vertebrates is of significant interest; however, most studies have been limited to bony vertebrates. With the influx of new publicly available cartilaginous fish genomes, we conducted the most comprehensive analysis of globin gene evolution in cartilaginous fish to date using phylogenetic, structural, and transcriptomic analyses. Our results shed light on similar and contrasting patterns of globin-gene evolution between cartilaginous and bony vertebrates and provide insight into the early evolution of globins in jawed vertebrates. Key-words: Globins, Cartilaginous Fish, Chondrichthyes, Gene Family Evolution

evolutionary biology↗

bioRxiv2025

Elevational variation in heart mass and suppression of hypoxia-induced right ventricle hypertrophy in Andean leaf-eared mice (Phyllotis)

In lowland mammals that ascend to high elevation, hypoxia-induced changes in the pulmonary circulation can give rise to hypoxic pulmonary hypertension (HPH) and associated right-ventricle (RV) hypertrophy. Some mammals that are native to high elevation have evolved a means of attenuating HPH, demonstrating how environmental adaptation may sometimes counteract the effects of ancestral acclimatization responses. Here, we examine elevational variation in heart mass and measures of RV hypertrophy in four closely related species of leaf-eared mice (genus Phyllotis) that are broadly co-distributed across a steep elevational gradient on the Western slope of the Andes. There was a positive relationship overall between heart mass and elevation that reflected proportional changes in both the right and left ventricles. Thus, elevation-related increases in overall heart mass were not generally attributable to RV hypertrophy, suggesting that this group of predominantly highland species have evolved a means of avoiding HPH and/or attenuating the cardiac response to HPH. To gain insight into possible transcriptional mechanisms, we examined patterns of transcriptomic variation in the right ventricles of Phyllotis vaccarum from two geographically distinct highland populations (both from elevations >5000 m) that exhibit strikingly different levels of RV hypertrophy. Suppression of RV hypertrophy is associated with differential expression of key regulatory genes involved in striated muscle, immune processes, and the inflammatory response. Analysis of co-expression modules identified a promising set of candidate genes for mediating the development of RV hypertrophy at extremely high elevations.

evolutionary biology↗

bioRxiv2025

Historical Contingency Shapes Toxin Resistance in a Specialist Avian Predator

Adaptations to toxic diets can cascade through ecosystems, altering physiology, species interactions, and trophic dynamics. To uncover the molecular basis of toxin resistance in the black-headed grosbeak (Pheucticus melanocephalus), a specialist predator of cardiotonic steroid-defended monarch butterflies (Danaus plexippus), we investigated the evolution of target-site insensitivity in the toxins molecular target - the Na,K-ATPase. Functional assays of engineered Na,K-ATPases revealed that resistance in grosbeaks arises from a non-additive interaction between a substitution at position 111 (Q111E) and up to six nearby amino acid changes in the first extracellular loop of the protein. Using resurrected ancestral proteins, we show that the earliest of these six substitutions to evolve (V113L) altered the functional effects of Q111E, such that Q111E alone became maladaptive. Only after the accumulation of additional permissive substitutions could Q111E confer resistance, highlighting how intramolecular epistatic interactions and historical contingency constrained the evolutionary path to adaptation. Our phylogenetic analysis of Na,K-ATPase sequences from 360 birds further revealed that several of the specific grosbeak substitutions--particularly at sites 112, 114, and 116--show strong signatures of co-evolution with changes at site 111 across the avian tree, supporting the hypothesis that resistance evolves through repeated, interacting changes. Together, these results reveal the molecular mechanisms of convergent evolution of toxin resistance and demonstrate how genetic background can shape evolutionary outcomes across trophic levels.

evolutionary biology↗

bioRxiv2024

Diet of Andean leaf-eared mice (Phyllotis) living at extreme elevations on Atacama volcanoes: insights from metagenomics, DNA metabarcoding, and stable isotopes

On the flanks of >6000 m Andean volcanoes that tower over the Atacama Desert, leaf-eared mice (Phyllotis vaccarum) live at extreme elevations that surpass known vegetation limits. What the mice eat in these barren, hyperarid environments has been the subject of much speculation. According to the arthropod fallout hypothesis, sustenance is provided by windblown insects that accumulate in snowdrifts ( aolian deposits). It is also possible that mice feed on saxicolous lichen or forms of cryptic vegetation that have yet to be discovered at such high elevations. We tested hypotheses about the diet of mice living at extreme elevations on Atacama volcanoes by combining metagenomic and DNA metabarcoding analyses of gut contents with stable-isotope analyses of mouse tissues. Genomic analyses of contents of the gastrointestinal tract of a live-captured mouse from the 6739 m summit of Volcan Llullaillaco revealed evidence for an opportunistic but purely herbivorous diet, including lichens. Although we found no evidence of animal DNA in gut contents of the summit mouse, stable isotope data indicate that mice native to elevations at or near vegetation limits ([~]5100 m) include a larger fraction of animal prey in their diet than mice from lower elevations. Some plant species detected in the gut contents of the summit mouse are known to exist at lower elevations at the base of the volcano and in the surrounding Altiplano, suggesting that such plants may occur at higher elevations beneath the snowpack or in other cryptic microhabitats.

evolutionary biology↗

bioRxiv2023

Genomic and Radiocarbon Insights into the Mystery of Mouse Mummies on the Summits of >6000 m Andean Volcanoes

Our understanding of the limits of animal life is continually revised by scientific exploration of extreme environments. Here we report the discovery of numerous mummified cadavers of leaf-eared mice, Phyllotis vaccarum, from the summits of three different Andean volcanoes at elevations 6029-6233 m (19,780-20,449 ft) above sea level in the Puna de Atacama (Chile-Argentina). Such extreme elevations were previously assumed to be completely uninhabitable by mammals. In combination with a live-captured specimen of the same species from the nearby summit of Volcan Llullaillaco (6739 m [=22,110 ft]), the 13 summit mummies represent the highest physical records of mammals in the world. We report a chromosome-level genome assembly for P. vaccarum in combination with a whole-genome re-sequencing analysis and radiocarbon dating analysis that provide insights into the provenance and antiquity of the summit mice. We test alternative hypotheses to explain the existence of mouse graveyards on the summits of Atacama volcanoes. Radiocarbon data indicate that the most ancient of the mummies were at most a few centuries old. Genomic polymorphism data revealed a high degree of continuity between the summit mice and conspecifics from lower elevations in the surrounding Altiplano. Genomic data also revealed equal numbers of males and females among the summit mice and evidence of close kinship between some individuals from the same summit groups. These findings bolster evidence for self-sustaining populations of Phyllotis at elevations >6000 m and challenge assumptions about the environmental limits of vertebrate life and the physiological tolerances of small mammals.

evolutionary biology↗

bioRxiv2023

Elevational and latitudinal range extensions of the puna mouse, Punomys (Cricetidae), with the first record of the genus from Chile

We report an elevational record for the Andean sigmodontine puna mouse Punomys, which is also the first record of the genus in Chile. The record is based on a mummified specimen that we discovered at an elevation of 5,461 m (17,917) in the caldera of Volcan Acamarachi, Region de Antofagasta, Chile. Results of a morphological suggest that the specimen can be provisionally referred to the species P. lemminus. This new record also extends the known geographic distribution of the genus by 700 km to the south and brings the known Chilean mammal richness to a total of 170 living species and 88 genera. This finding highlights the need for increased survey efforts in more remote, high-elevation regions and demonstrates that there is still much to be learned about the mammal fauna of the Andean Altiplano.

zoology↗

bioRxiv2022

Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice

Phenotypic plasticity can play an important role in the ability of animals to tolerate environmental stress, but the nature and magnitude of plastic responses are often specific to the developmental timing of exposure. Here, we examine changes in gene expression in the diaphragm of highland deer mice (Peromyscus maniculatus) in response to hypoxia exposure at different stages of development. In highland deer mice, developmental plasticity in diaphragm function may mediate changes in several respiratory traits that influence aerobic metabolism and performance under hypoxia. We generated RNAseq data from diaphragm tissue of adult deer mice exposed to 1) life-long hypoxia (before conception to adulthood), 2) post-natal hypoxia (birth to adulthood), 3) adult hypoxia (6-8 weeks only during adulthood), or 4) normoxia. We found five suites of co-regulated genes that are differentially expressed in response to hypoxia, but the patterns of differential expression depend on the developmental timing of exposure. We also identified four transcriptional modules that are associated with important respiratory traits. Many of the genes in these transcriptional modules bear signatures of altitude-related selection, providing an indirect line of evidence that observed changes in gene expression may be adaptive in hypoxic environments. Our results demonstrate the importance of developmental stage in determining the phenotypic response to environmental stressors.

molecular biology↗

bioRxiv2022

Epistatic effects between amino acid insertions and substitutions mediate toxin-resistance of vertebrate Na+,K+-ATPases

The recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse animals most frequently involves convergent amino-acid substitutions to the H1-H2 extracellular loop of Na+,K+-ATPase (NKA). Previous work established that hystricognath rodents (e.g. chinchilla) and pterocliform birds (sandgrouse) have convergently evolved amino-acid insertions in the H1-H2 loop, but their functional significance is not known. Using protein engineering, we show that these insertions have distinct effects on CTS resistance of NKA in the two lineages that strongly depend on intramolecular interactions with other residues. Removing the insertion in the chinchilla lineage unexpectedly increases CTS resistance and decreases NKA activity. In the sandgrouse lineage, the insertion works in concert with the substitution Q111R to increase CTS resistance while maintaining wild-type ATPase activity levels. Molecular docking simulations provide additional insight into the biophysical mechanisms responsible for the context-specific CTS insensitivity of the enzyme. Our results highlight the diversity of genetic substrates that underlie CTS insensitivity in vertebrate NKA and reveal how amino-acid insertions can alter the phenotypic effects of point mutations at key sites in the same protein domain.

evolutionary biology↗

bioRxiv2022

Evolution and molecular basis of a novel allosteric property of crocodilian hemoglobin

Understanding the evolution of novel protein functions requires data on the mechanistic effects of causative mutations and the extent of coupling between the gain of new function and loss of ancestral function. Here, we use ancestral protein resurrection and directed mutagenesis to dissect the molecular basis of a novel mode of allosteric regulation in crocodilian hemoglobin. We discovered that regulation of Hb-O2 affinity via allosteric binding of bicarbonate ions (a biochemical adaptation unique to crocodilians) and the concomitant loss of allosteric regulation by ATP-binding are attributable to non-overlapping sets of substitutions. Gain of bicarbonate-sensitivity involved direct effects of few replacements at key sites in combination with indirect effects of numerous replacements at structurally disparate sites. Due to the context-dependence of causative substitutions, the unique allosteric properties of crocodilian hemoglobin cannot be easily transplanted into divergent homologs of other species. Significance StatementThe extraordinary breath-hold diving capacity of crocodilians is partly attributable to a unique mode of allosterically regulating hemoglobin-oxygenation in circulating red blood cells. We investigated the origin and mechanistic basis of this novel biochemical adaptation by performing directed mutagenesis experiments on resurrected ancestral crocodilian hemoglobins. Our results revealed that evolved changes in allosteric regulation involved the direct effect of few amino acid substitutions at key sites in combination with indirect effects of numerous other substitutions at structurally disparate sites. Such indirect interaction effects suggest that the evolution of novel protein functions may often depend on neutral mutations that produce no adaptive benefit when they first arise, but which contribute to a permissive background for subsequent function-altering mutations at other sites.

evolutionary biology↗

bioRxiv2021

Blood variation implicates respiratory limits on elevational ranges of Andean birds

The extent to which species ranges reflect intrinsic physiological tolerances is a major, unsolved question in evolutionary ecology. To date, consensus has been hindered by the limited tractability of experimental approaches across most of the tree of life. Here, we apply a macrophysiological approach to understand how hematological traits related to oxygen transport shape elevational ranges in a tropical biodiversity hotspot. Along Andean elevational gradients, we measured traits that affect blood oxygen-carrying capacity--total and cellular hemoglobin concentration and hematocrit--for 2,355 individuals of 136 bird species. We used these data to evaluate the influence of hematological traits on elevational ranges. First, we asked whether hematological plasticity is predictive of elevational range breadth. Second, we asked whether variance in hematological traits changed as a function of distance from the midpoint of the elevational range. We found that the correlation between hematological plasticity and elevational range breadth was slightly positive, consistent with a facilitative role for plasticity in elevational range expansion. We further found reduced local variation in hematological traits near elevational range limits and at high elevations, patterns consistent with intensified natural selection, reduced effective population size, or compensatory changes in other cardiohematological traits with increasing distance from species-specific optima for oxygen availability. Our findings suggest that constraints on hematological plasticity and local genetic adaptation to oxygen availability promote the evolution of the narrow elevational ranges that underpin tropical montane biodiversity.

ecology↗

bioRxiv2021

High-altitude adaptation and incipient speciation in geladas

Survival at high altitude requires adapting to extreme conditions such as environmental hypoxia. To understand high-altitude adaptations in a primate, we assembled the genome of the gelada (Theropithecus gelada), an endemic Ethiopian monkey, and complemented it with population resequencing, hematological, and morphometric data. Unexpectedly, we identified a novel karyotype that may contribute to reproductive isolation between gelada populations. We also identified genomic elements including protein-coding sequences and gene families that exhibit accelerated changes in geladas and may contribute to high-altitude adaptation. Our findings lend insight into mechanisms of speciation and adaptation while providing promising avenues for functional hypoxia research.

genomics↗

bioRxiv2021

New insights into the allosteric effects of CO2 and bicarbonate on crocodilian hemoglobin

Crocodilians are unique among vertebrates in that their hemoglobin (Hb) O2 binding is allosterically regulated by bicarbonate, which forms in the red blood cell upon hydration of CO2. Although known for decades, this remarkable mode of allosteric control has not yet been experimentally verified with direct evidence of bicarbonate binding to crocodilian Hb, probably because of confounding CO2-mediated effects. Here we provide the first quantitative analysis of the separate allosteric effects of CO2 and bicarbonate on Hb of the spectacled caiman (Caiman crocodilus). Using thin-layer gas diffusion chamber and Tucker chamber techniques, we demonstrate that both CO2 and bicarbonate bind to Hb with high affinity and strongly decrease Hb-O2 saturation, and propose that both effectors bind to an unidentified positively charged site containing a reactive amino group in the low-O2 affinity T conformation of the Hb. These results provide the first experimental evidence that bicarbonate binds directly to crocodilian Hb and promotes O2 delivery independently of CO2. Using the gas-diffusion chamber, we observed similar effects in the Hbs of a phylogenetically diverse set of other caiman, alligator, and crocodile species, suggesting that the unique mode of allosteric regulation by CO2 and bicarbonate evolved >80-100 million years ago in the common ancestor of crocodilians. Taken together, our results show a tight and unusual linkage between O2 and CO2 transport in the blood of crocodilians, where build-up of blood CO2 and bicarbonate ions during breath-hold diving or digestion facilitates O2 delivery, while Hb desaturation facilitates CO2 transport as protein-bound CO2 and bicarbonate.

physiology↗

bioRxiv2021

Genetic variation in haemoglobin regulates breathing in high-altitude deer mice

Physiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated the in vivo effects on respiratory physiology of genetic variants in haemoglobin (Hb) that contribute to hypoxia adaptation in high-altitude deer mice (Peromyscus maniculatus). We created F2 inter-population hybrids of highland and lowland deer mice to test the phenotypic effects of - and {beta}-globin variants on a mixed genetic background. High-altitude genotypes were associated with breathing phenotypes that enhance O2 uptake in hypoxia, including a deeper more effective breathing pattern and an augmented hypoxic ventilatory response. These effects could not be explained by erythrocyte Hb-O2 affinity or globin gene expression in the brainstem. Therefore, adaptive variation in haemoglobin can have unexpected effects on physiology that are distinct from the canonical function of this protein in circulatory O2 transport.

evolutionary biology↗

bioRxiv2020

Evolved increases in hemoglobin-oxygen affinity and Bohr effect coincided with the aquatic specialization of penguins.

Dive capacities of air-breathing vertebrates are dictated by onboard O2 stores, suggesting that physiological specializations of diving birds like penguins may have involved adaptive changes in convective O2 transport. It has been hypothesized that increased hemoglobin (Hb)-O2 affinity improves pulmonary O2 extraction and enhance capacities for breath-hold diving. To investigate evolved changes in Hb function associated with the aquatic specialization of penguins, we integrated comparative measurements of whole-blood and purified native Hbs with protein engineering experiments based on site-directed mutagenesis. We reconstructed and resurrected ancestral Hbs representing the common ancestor of penguins and the more ancient ancestor shared by penguins and their closest nondiving relatives (order Procellariiformes, which includes albatrosses, shearwaters, petrels, and storm petrels). These two ancestors bracket the phylogenetic interval in which penguin-specific changes in Hb function would have evolved. The experiments revealed that penguins evolved a derived increase in Hb-O2 affinity and a greatly augmented Bohr effect (reduced Hb-O2 affinity at low pH). Although an increased Hb-O2 affinity reduces the gradient for O2 diffusion from systemic capillaries to metabolizing cells, this can be compensated by a concomitant enhancement of the Bohr effect, thereby promoting O2 unloading in acidified tissues. We suggest that the evolved increase in Hb-O2 affinity in combination with the augmented Bohr effect maximizes both O2 extraction from the lungs and O2 unloading from the blood, allowing penguins to fully utilize their onboard O2 stores and maximize underwater foraging time.

evolutionary biology↗

bioRxiv2020

The adaptive benefit of increases in hemoglobin-O2 affinity is contingent on tissue O2 diffusing capacity in high-altitude deer mice

BackgroundComplex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2 consumption, V{square}O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2 inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2 affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2 transport pathway to examine links between cardiorespiratory traits and V{square}O2max. ResultsPhysiological experiments revealed that increases in Hb-O2 affinity of red blood cells improved blood oxygenation in hypoxia, but were not associated with an enhancement in V{square}O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2 affinity on V{square}O2max in hypoxia was contingent on the capacity for O2 diffusion in active tissues. ConclusionsThese results suggest that increases in Hb-O2 affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2 diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2 affinity is contingent on the capacity to extract O2 from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.

physiology↗

bioRxiv2020

Concerted evolution reveals co-adapted amino acid substitutions in frogs that prey on toxic toads

Gene duplication is an important source of evolutionary innovation, but the adaptive division-of-labor between duplicates can be opposed by ongoing gene conversion between them. Here we document a tandem duplication of Na+,K+-ATPase subunit 1 (ATP1A1) shared by frogs in the genus Leptodactylus, a group of species that feeds on toxic toads. One ATP1A1 paralog evolved resistance to toad toxins while the other paralog retained ancestral susceptibility. We show that the two Leptodactylus paralogs are distinguished by 12 amino acid substitutions that were maintained by strong selection that counteracted the homogenizing effect of gene conversion. Protein-engineering experiments show that two major-effect substitutions confer toxin resistance, whereas the 10 additional substitutions mitigate deleterious pleiotropic effects on enzyme function. Our results highlight how trans-specific, neofunctionalized gene duplicates can provide unique insights into interactions between adaptive substitutions and the genetic backgrounds on which they arise. One Sentence SummarySelection counteracts gene conversion to maintain an adaptive division-of-labor between tandemly duplicated genes.

evolutionary biology↗

bioRxiv2020

Biochemical paedomorphosis and genetic assimilation in the hypoxia adaptation of Tibetan antelope

Developmental shifts in stage-specific gene expression can provide a ready mechanism of phenotypic change by altering the rate or timing of ontogenetic events. We discovered that the high-altitude Tibetan antelope (Panthelops hodgsonii) has evolved an adaptive increase in blood-O2 affinity by truncating the ancestral ontogeny of globin gene expression such that a high-affinity juvenile hemoglobin isoform (isoHb) completely supplants the lower-affinity isoHb that is expressed in the adult red blood cells of other bovids. This juvenilization of blood properties represents a canalization of an acclimatization response to hypoxia that has been well-documented in adult goats and sheep. We also discovered the genomic mechanism underlying this regulatory isoHb switch, revealing how a reversible acclimatization response became genetically assimilated as an irreversible adaptation to chronic hypoxia.

evolutionary biology↗

bioRxiv2020

Discovery of the world's highest-dwelling mammal

Environmental limits of animal life are invariably revised upwards when the animals themselves are investigated in their natural habitats. Here we report results of a scientific mountaineering expedition to survey the high-altitude rodent fauna of Volcan Llullaillaco in the Puna de Atacama of northern Chile, an effort motivated by video documentation of mice (genus Phyllotis) at a record altitude of 6205 m. Among numerous trapping records at altitudes >5000 m, we captured a specimen of the yellow-rumped leaf-eared mouse (Phyllotis xanthopygus rupestris) on the very summit of Llullaillaco at 6739 m. This summit specimen represents an altitudinal world record for mammals, far surpassing all specimen-based records from the Himalayas and elsewhere in the Andes. This discovery suggests that we may have generally underestimated the altitudinal range limits and physiological tolerances of small mammals simply because the worlds highest summits remain relatively unexplored by biologists.

evolutionary biology↗