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Larracuente, Amanda (Ed.)Abstract Given the many levels of biological variation in mutation rates observed to date in primates—spanning from species to individuals to genomic regions—future steps in our understanding of mutation rate evolution will not only be aided by a greater breadth of species coverage across the primate clade but also by a greater depth as afforded by an evaluation of multiple trios within individual species. In order to help bridge these gaps, we here present an analysis of a species representing one of the most basal splits on the primate tree (aye-ayes), combining whole-genome sequencing of seven parent–offspring trios from a three-generation pedigree with a novel computational pipeline that takes advantage of recently developed pan-genome graphs, thereby circumventing the application of (highly subjective) quality metrics that has previously been shown to result in notable differences in the detection of de novo mutations and ultimately estimates of mutation rates. This deep sampling has enabled both a detailed picture of parental age effects and sex dependency in mutation rates, which we here compare with previously studied primates, but has also provided unique insights into the nature of genetic variation in one of the most endangered primates on the planet.more » « lessFree, publicly-accessible full text available March 1, 2026
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Given the many levels of biological variation in mutation rates observed to date in primates – spanning from species to individuals to genomic regions – future steps in our understanding of mutation rate evolution will be aided by both a greater breadth of species coverage across the primate clade, but also by a greater depth as afforded by an evaluation of multiple trios within individual species. In order to help bridge these gaps, we here present an analysis of a species representing one of the most basal splits on the primate tree (aye-ayes), combining whole-genome sequencing of seven parent-offspring trios from a three-generation pedigree with a novel computational pipeline that takes advantage of recently developed pan-genome graphs, thereby circumventing the application of (highly subjective) quality metrics that has previously been shown to result in notable differences in the detection of de novo mutations, and ultimately estimates of mutation rates. This deep sampling has enabled both a detailed picture of parental age effects as well as sex dependency in mutation rates which we here compare with previously studied primates, but has also provided unique insights into the nature of genetic variation in one of the most endangered primates on the planet.more » « lessFree, publicly-accessible full text available November 11, 2025
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Free, publicly-accessible full text available December 1, 2025
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Abstract The dwarf lemurs (Cheirogaleusspp.) of Madagascar are the only obligate hibernators among primates. Despite century‐old field accounts of seasonal lethargy, and more recent evidence of hibernation in the western fat‐tailed dwarf lemur (Cheirogaleus medius), inducing hibernation in captivity remained elusive for decades. This included the Duke Lemur Center (DLC), which maintains fat‐tailed dwarf lemurs and has produced sporadic research on reproduction and metabolism. With cumulative knowledge from the field, a newly robust colony, and better infrastructure, we recently induced hibernation in DLC dwarf lemurs. We describe two follow‐up experiments in subsequent years. First, we show that dwarf lemurs under stable cold conditions (13°C) with available food continued to eat daily, expressed shallower and shorter torpor bouts, and had a modified gut microbiome compared to peers without food. Second, we demonstrate that dwarf lemurs under fluctuating temperatures (12–30°C) can passively rewarm daily, which was associated with altered patterns of fat depletion and reduced oxidative stress. Despite the limitations of working with endangered primates, we highlight the promise of studying hibernation in captive dwarf lemurs. Follow‐up studies on genomics and epigenetics, metabolism, and endocrinology could have relevance across multidisciplinary fields, from biomedicine to evolutionary biology, and conservation.more » « less
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Using DNA methylation profiles (n= 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels inHOXLsubclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.more » « less
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