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1. Evolutionary constraint and innovation across hundreds of placental mammals

   https://doi.org/10.1126/science.abn3943  

   Christmas, Matthew J.; Kaplow, Irene M.; Genereux, Diane P.; Dong, Michael X.; Hughes, Graham M.; Li, Xue; Sullivan, Patrick F.; Hindle, Allyson G.; Andrews, Gregory; Armstrong, Joel C.; et al (April 2023, Science)

   INTRODUCTION A major challenge in genomics is discerning which bases among billions alter organismal phenotypes and affect health and disease risk. Evidence of past selective pressure on a base, whether highly conserved or fast evolving, is a marker of functional importance. Bases that are unchanged in all mammals may shape phenotypes that are essential for organismal health. Bases that are evolving quickly in some species, or changed only in species that share an adaptive trait, may shape phenotypes that support survival in specific niches. Identifying bases associated with exceptional capacity for cellular recovery, such as in species that hibernate, could inform therapeutic discovery. RATIONALE The power and resolution of evolutionary analyses scale with the number and diversity of species compared. By analyzing genomes for hundreds of placental mammals, we can detect which individual bases in the genome are exceptionally conserved (constrained) and likely to be functionally important in both coding and noncoding regions. By including species that represent all orders of placental mammals and aligning genomes using a method that does not require designating humans as the reference species, we explore unusual traits in other species. RESULTS Zoonomia’s mammalian comparative genomics resources are the most comprehensive and statistically well-powered produced to date, with a protein-coding alignment of 427 mammals and a whole-genome alignment of 240 placental mammals representing all orders. We estimate that at least 10.7% of the human genome is evolutionarily conserved relative to neutrally evolving repeats and identify about 101 million significantly constrained single bases (false discovery rate < 0.05). We cataloged 4552 ultraconserved elements at least 20 bases long that are identical in more than 98% of the 240 placental mammals. Many constrained bases have no known function, illustrating the potential for discovery using evolutionary measures. Eighty percent are outside protein-coding exons, and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Constrained bases tend to vary less within human populations, which is consistent with purifying selection. Species threatened with extinction have few substitutions at constrained sites, possibly because severely deleterious alleles have been purged from their small populations. By pairing Zoonomia’s genomic resources with phenotype annotations, we find genomic elements associated with phenotypes that differ between species, including olfaction, hibernation, brain size, and vocal learning. We associate genomic traits, such as the number of olfactory receptor genes, with physical phenotypes, such as the number of olfactory turbinals. By comparing hibernators and nonhibernators, we implicate genes involved in mitochondrial disorders, protection against heat stress, and longevity in this physiologically intriguing phenotype. Using a machine learning–based approach that predicts tissue-specific cis - regulatory activity in hundreds of species using data from just a few, we associate changes in noncoding sequence with traits for which humans are exceptional: brain size and vocal learning. CONCLUSION Large-scale comparative genomics opens new opportunities to explore how genomes evolved as mammals adapted to a wide range of ecological niches and to discover what is shared across species and what is distinctively human. High-quality data for consistently defined phenotypes are necessary to realize this potential. Through partnerships with researchers in other fields, comparative genomics can address questions in human health and basic biology while guiding efforts to protect the biodiversity that is essential to these discoveries. Comparing genomes from 240 species to explore the evolution of placental mammals. Our new phylogeny (black lines) has alternating gray and white shading, which distinguishes mammalian orders (labeled around the perimeter). Rings around the phylogeny annotate species phenotypes. Seven species with diverse traits are illustrated, with black lines marking their branch in the phylogeny. Sequence conservation across species is described at the top left. IMAGE CREDIT: K. MORRILL 

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2. Universal phylogenetic inertia in body temperature evolution across endothermic and ectothermic tetrapods

   https://doi.org/10.1101/2025.10.27.684885  

   Tarimo, Eliza; White, Emma; Bodensteiner, Brooke L; Muñoz, Martha M; Waldron, Brian P; Uyeda, Josef C (October 2025, bioRxiv)

   Abstract Species must adapt to persist in a changing world. As global temperatures rise, how species adapt and respond to thermal shifts is crucial for anticipating global patterns of biodiversity change. Land vertebrates can be divided into two major thermoregulatory strategies, endothermy and ectothermy. One might hypothesize that, given their reputation as being “cold blooded,” ectotherms are thermal generalists, capable of operating across a greater range of body temperatures than endotherms and exhibit greater plasticity and evolvability in body temperature. However, a wide variety of traits and ecologies could modulate responses of thermal physiology to environmental change. Here, we employ macroevolutionary models to estimate the rate of adaptation of thermal physiology across squamates, mammals, and birds in the context of their ecology, physiology, and changing climatic conditions and whether there are fundamental differences in how the three clades respond to their environments. We find stronger relationships between squamates’ body temperature and their environment than in birds and mammals, significant effects of diel activity (nocturnal and diurnal) on body temperature evolution in all clades, and no effect of aquatic/terrestrial habits and rumination on the evolution of body temperature in mammals. Most surprisingly, our findings suggest shared limits on the evolution of thermal physiology across ectothermic and endothermic groups that argue for universal constraints on the rate of evolution in thermal physiology while explaining disparate patterns of body temperature and niche evolution across groups. 

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3. Fundamental constraints on vertebrate life history are shaped by aquatic–terrestrial transitions and reproductive mode

   https://doi.org/10.1038/s41559-025-02663-1  

   Brooks, George C; Uyeda, Josef C; Bone, Nicholas J; Conrad, Hailey M; Mull, Christopher G; Kindsvater, Holly K (May 2025, Nature Ecology & Evolution)

   Vertebrate life histories evolve in response to selection imposed by abiotic and biotic environmental conditions while being limited by genetic, developmental, physiological, demographic and phylogenetic processes that constrain adaptation. Despite the well-recognized shifts in selective pressures accompanying transitions among environments, the conditions driving innovation and the consequences for life-history evolution remain outstanding questions. Here we compare the traits of vertebrates that occupy aquatic or terrestrial environments as juveniles to infer shifts in evolutionary constraints that explain differences in their life-history traits and thus their fundamental demographic rates. Our results emphasize the reduced potential for life-history diversification on land, especially that of reproductive strategies, which limits the scope of viable life-history strategies. Moreover, our study reveals differences between the evolution of viviparity in aquatic and terrestrial realms. Transitions from egg laying to live birth represent a major shift across life-history space for aquatic organisms, whereas terrestrial egg-laying organisms evolve live birth without drastic changes in life-history strategy. Whilst trade-offs in the allocation of resources place fundamental constraints on the way life histories can vary, ecological setting influences the position of species within the viable phenotypic space available for adaptive evolution. 

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4. Spatial information from the odour environment in mammalian olfaction

   https://doi.org/10.1007/s00441-020-03395-3  

   Marin, Alina Cristina; Schaefer, Andreas T; Ackels, Tobias (January 2021, Cell and Tissue Research)

   null (Ed.)

   Abstract The sense of smell is an essential modality for many species, in particular nocturnal and crepuscular mammals, to gather information about their environment. Olfactory cues provide information over a large range of distances, allowing behaviours ranging from simple detection and recognition of objects, to tracking trails and navigating using odour plumes from afar. In this review, we discuss the features of the natural olfactory environment and provide a brief overview of how odour information can be sampled and might be represented and processed by the mammalian olfactory system. Finally, we discuss recent behavioural approaches that address how mammals extract spatial information from the environment in three different contexts: odour trail tracking, odour plume tracking and, more general, olfactory-guided navigation. Recent technological developments have seen the spatiotemporal aspect of mammalian olfaction gain significant attention, and we discuss both the promising aspects of rapidly developing paradigms and stimulus control technologies as well as their limitations. We conclude that, while still in its beginnings, research on the odour environment offers an entry point into understanding the mechanisms how mammals extract information about space. 

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5. The Role of the Stimulus in Olfactory Plasticity

   https://doi.org/10.3390/brainsci13111553  

   Coppola, David M.; Reisert, Johannes (November 2023, Brain Sciences)

   Cheetham, Claire E. (Ed.)

   Plasticity, the term we use to describe the ability of a nervous system to change with experience, is the evolutionary adaptation that freed animal behavior from the confines of genetic determinism. This capacity, which increases with brain complexity, is nowhere more evident than in vertebrates, especially mammals. Though the scientific study of brain plasticity dates back at least to the mid-19th century, the last several decades have seen unprecedented advances in the field afforded by new technologies. Olfaction is one system that has garnered particular attention in this realm because it is the only sensory modality with a lifelong supply of new neurons, from two niches no less! Here, we review some of the classical and contemporary literature dealing with the role of the stimulus or lack thereof in olfactory plasticity. We have restricted our comments to studies in mammals that have used dual tools of the field: stimulus deprivation and stimulus enrichment. The former manipulation has been implemented most frequently by unilateral naris occlusion and, thus, we have limited our comments to research using this technique. The work reviewed on deprivation provides substantial evidence of activity-dependent processes in both developing and adult mammals at multiple levels of the system from olfactory sensory neurons through to olfactory cortical areas. However, more recent evidence on the effects of deprivation also establishes several compensatory processes with mechanisms at every level of the system, whose function seems to be the restoration of information flow in the face of an impoverished signal. The results of sensory enrichment are more tentative, not least because of the actual manipulation: What odor or odors? At what concentrations? On what schedule? All of these have frequently not been sufficiently rationalized or characterized. Perhaps it is not surprising, then, that discrepant results are common in sensory enrichment studies. Despite this problem, evidence has accumulated that even passively encountered odors can “teach” olfactory cortical areas to better detect, discriminate, and more efficiently encode them for future encounters. We discuss these and other less-established roles for the stimulus in olfactory plasticity, culminating in our recommended “aspirations” for the field going forward. 

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