Biology subjects

Bautista, N. M.

Publications and source records attributed to Bautista, N. M..

9 recordsLinked to original sources

bioRxiv2026

Origins of allostery in vertebrate hemoglobin evolution

Allostery is an essential and structurally complex form of biochemical regulation, but how allosteric proteins evolved from nonallosteric precursors is unknown. Vertebrate hemoglobin (Hb), a symmetrical tetramer, binds organic phosphates in a central cavity between subunits, which reduces its oxygen affinity. Using ancestral protein reconstruction, we show that Hb's historical precursor, a non-allosteric dimer, was fortuitously on the evolutionary edge of allostery: just three historical substitutions can confer allostery upon it -- one that causes tetramerization, and two others that create an effector-binding site in the cavity. The ancient tetramer could also have acquired inverse allostery -- effector binding that improves oxygen affinity -- via a single substitution that moves the binding site deeper in the cavity. These short evolutionary paths were possible because a key prerequisite for allostery -- propensity to occupy multiple conformations that change upon oxygen binding -- is an intrinsic, ancient property of the globin fold. Evolution of symmetric tetramerization caused this tertiary lability to propagate into oxygen-linked quaternary changes affecting the cavity, so the only remaining requirement for allostery was effector binding. Conformational heterogeneity and multimeric symmetry are widespread, suggesting that many allosteric proteins may have evolved by simple mechanisms from precursors fortuitously poised on the edge of allostery.

evolutionary biology↗

bioRxiv2026

CLIMATIC NICHE DIFFERENTIATION ACCOMPANIED THE RADIATION OF LEAF-EARED MICE IN THE PHYLLOTIS DARWINI SPECIES GROUP (SIGMODONTINAE, CRICETIDAE)

Aimto characterize the evolution of climatic niches during the diversification of the Phyllotis darwini species group, in order to assess the extent to which divergences involved in radiation were associated with patterns of conservatism or divergence of climatic niches, and whether the differentiation found among climatic niches correlated with species phylogenetic relationships. Locationsouth-central Andes, surrounding lowlands, and Patagonia, South America. Methodsspecies climatic niches were characterized by sampling contemporaneous precipitation and temperature conditions across occurrence locations and entire distributional ranges. Climatic niches were analyzed and modeled using multivariate statistics (PCA, PERMANOVA), a maximum entropy-based algorithm, and novel methods developed to explore levels of differentiation (niche overlap test) and divergence (niche divergence test) between realized and fundamental niches. Comparative phylogenetic methods were applied using a time-calibrated phylogeny and integrating climate niche data to estimate ancestral environmental niches within geographic and environmental spaces. Resultscomparisons revealed low levels of climatic niche overlap, both among species realized niches and among their fundamental niches, suggesting high levels of niche differentiation during the diversification of Phyllotis species. Quantifications of niche overlap further showed that observed differences among species lay primarily in the multidimensional nature of climatic niches, as unidimensional quantifications exhibited higher levels of overlap. Evolved differences among species climatic niches were better fitted to a Brownian motion model of evolution, but lacked phylogenetic signal and showed no significant association with species phylogenetic distances. Main conclusionslow levels of differentiation between ancestral climatic niches suggest that the early radiation of species in the Phyllotis darwini species group was promoted by geographic isolation, whereas the more recent diversification of extant species was accompanied by climatic niche differentiation, possibly involving local adaptation to regional ecoclimatic changes associated with Quaternary glacial cycles. The spatial separation of sister species, the complete divergence of their climatic niches, and the lack of phylogenetic signal in niche differences suggest a scenario of diversification in which divergences were prompted by the spatial isolation, but also by the divergent selection exerted by regional climatic differences.

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↗

bioRxiv2024

Species limits and hybridization in Andean leaf-eared mice (Phyllotis)

Leaf-eared mice (genus Phyllotis) are among the most widespread and abundant small mammals in the Andean Altiplano, but species boundaries and distributional limits are often poorly delineated due to sparse survey data from remote mountains and high-elevation deserts. Here we report a combined analysis of mitochondrial DNA variation and whole-genome sequence (WGS) variation in Phyllotis mice to delimit species boundaries, to assess the timescale of diversification of the group, and to examine evidence for interspecific hybridization. Estimates of divergence dates suggest that most diversification of Phyllotis occurred during the past 3 million years. Consistent with the Pleistocene Aridification hypothesis, our results suggest that diversification of Phyllotis largely coincided with climatically induced environmental changes in the mid- to late Pleistocene. Contrary to the Montane Uplift hypothesis, most diversification in the group occurred well after the major phase of uplift of the Central Andean Plateau. Species delimitation analyses revealed surprising patterns of cryptic diversity within several nominal forms, suggesting the presence of much undescribed alpha diversity in the genus. Results of genomic analyses revealed evidence of ongoing hybridization between the sister species Phyllotis limatus and P. vaccarum and suggest that the contemporary zone of range overlap between the two species represents an active hybrid zone.

evolutionary biology↗

bioRxiv2024

Local adaptation, plasticity, and evolved resistance to hypoxic cold stress in high-altitude deer mice

A fundamental question in evolutionary biology concerns the relative contributions of phenotypic plasticity vs. local adaptation (genotypic specialization) in enabling wide-ranging species to inhabit diverse environmental conditions. Here we conduct a long-term hypoxia acclimation experiment to assess the relative roles of local adaptation and plasticity in enabling highland and lowland deer mice (Peromyscus maniculatus) to sustain aerobic thermogenesis at progressively increasing elevations. We assessed the relative physiological performance capacities of highland and lowland natives as they were exposed to progressive, stepwise increases in hypoxia, simulating the gradual ascent from sea level to an elevation of 6000 m. The final elevation of 6000 m far exceeds the highest attainable elevations within the species range, and therefore tests the animals ability to tolerate levels of hypoxia that surpass the prevailing conditions within their current distributional limits. Our results demonstrate that highland natives exhibit superior thermogenic capacities at the most severe levels of hypoxia, suggesting that the species broad fundamental niche and its ability to inhabit such a broad range of elevational zones is attributable to a combination of genetically based local adaptation and plasticity. Transcriptomic and physiological measurements identify evolved changes in the acclimation response to hypoxia that contribute to the enhanced thermogenic capacity of highland natives. SIGNIFICANCE STATEMENTIn species that are distributed across steep environmental gradients, the ability to inhabit a broad range of conditions may be attributable to local adaptation and/or a generalized acclimatization capacity (phenotypic plasticity). By experimentally acclimating highland and lowland deer mice (Peromyscus maniculatus) to progressively increasing levels of hypoxia during a simulated ascent to 6000 m, we assessed the relative roles of evolved and plastic changes in thermogenic capacity. At especially severe levels of hypoxia, the superior thermogenic performance of highland natives relative to lowland conspecifics suggests that the broad fundamental niche of deer mice is largely attributable to local adaptation to different elevational zones, including evolved plasticity in gene expression and respiratory traits.

evolutionary biology↗

bioRxiv2023

Extreme high-elevation mammal surveys reveal unexpectedly high upper range limits of Andean mice

In the worlds highest mountain ranges, uncertainty about the upper elevational range limits of alpine animals represents a critical knowledge gap regarding the environmental limits of life and presents a problem for detecting range shifts in response to climate change. Here we report results of mountaineering mammal surveys in the Central Andes, which led to the discovery of multiple species of mice living at extreme elevations that far surpass previously assumed range limits for mammals. We live-trapped small mammals from ecologically diverse sites spanning >6700 m of vertical relief, from the desert coast of northern Chile to the summits of the highest volcanoes in the Andes. We used molecular sequence data and whole-genome sequence data to confirm the identities of species that represent new elevational records and to test hypotheses regarding species limits. These discoveries contribute to a new appreciation of the environmental limits of vertebrate life.

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↗

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

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↗