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1. Characterizing the Rates and Patterns of De Novo Germline Mutations in the Aye-Aye ( Daubentonia madagascariensis )

   https://doi.org/10.1093/molbev/msaf034  

   Versoza, Cyril J; Ehmke, Erin E; Jensen, Jeffrey D; Pfeifer, Susanne P (March 2025, Molecular Biology and Evolution)

   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. 

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2. Characterizing the rates and patterns of de novo germline mutations in coppery titi monkeys (Plecturocebus cupreus)

   https://doi.org/10.64898/2026.01.15.699688  

   Versoza, Cyril J; Bales, Karen L; Jensen, Jeffrey D; Pfeifer, Susanne P (January 2026, bioRxiv)

   ABSTRACT Although recent advances in genomics have enabled the high-resolution study of whole genomes, our understanding of one of the key evolutionary processes, mutation, still remains limited. In primates specifically, studies have largely focused on humans and their closest evolutionary relatives, the great apes, as well as a handful of species of biomedical or conservation interest. Yet, as biological variation in mutation rates has been shown to vary across genomic regions, individuals, and species, a greater understanding of the underlying evolutionary dynamics at play will ultimately be illuminated by not only additional sampling across the Order, but also by a greater depth of sampling within-species. To address these needs, we here present the first population-scale genomic resources for a platyrrhine of considerable biomedical interest for both social behavior and neurobiology, the coppery titi monkey (Plecturocebus cupreus). Deep whole-genome sequencing of 15 parent-offspring trios, together with a computationalde novomutation detection pipeline based on pan-genome graphs, has provided a detailed picture of the sex-averaged mutation rate — 0.63 × 10^-8(95% CI: 0.43 × 10^-8– 0.90 × 10^-8) per site per generation — as well as the effects of both sex and parental age on underlying rates, demonstrating a significant paternal age effect. Coppery titi monkey males exhibit long reproductive lifespans, afforded by long-term pair bonding in the species’ monogamous mating system, and our results have demonstrated that individuals reproducing later in life exhibit one of the strongest male mutation biases observed in any non-human primate studied to date. Taken together, this study thus provides an important piece of the puzzle for better comprehending the mutational landscape across primates. 

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3. Inferring fine-scale mutation and recombination rate maps in aye-ayes (Daubentonia madagascariensis)

   https://doi.org/10.1101/2024.12.28.630620  

   Soni, Vivak; Versoza, Cyril J; Terbot, John W; Jensen, Jeffrey D; Pfeifer, Susanne P (December 2024, bioRxiv)

   The rate of input of new genetic mutations, and the rate at which that variation is reshuffled, are key evolutionary processes shaping genomic diversity. Importantly, these rates vary not just across populations and species, but also across individual genomes. Despite previous studies having demonstrated that failing to account for rate heterogeneity across the genome can bias the inference of both selective and neutral population genetic processes, mutation and recombination rate maps have to date only been generated for a relatively small number of organisms. Here, we infer such fine-scale maps for the aye-aye (Daubentonia madagascariensis) – a highly endangered strepsirrhine that represents one of the earliest splits in the primate clade, and thus stands as an important outgroup to the more commonly-studied haplorrhines – utilizing a recently released fully-annotated genome combined with high-quality population sequencing data. We compare our indirectly inferred rates to previous pedigree-based estimates, finding further evidence of relatively low mutation and recombination rates in aye-ayes compared to other primates. 

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4. Inferring Fine‐Scale Mutation and Recombination Rate Maps in Aye‐Ayes ( Daubentonia madagascariensis )

   https://doi.org/10.1002/ece3.72314  

   Soni, Vivak; Versoza, Cyril J; Terbot, John W; Jensen, Jeffrey D; Pfeifer, Susanne P (November 2025, Ecology and Evolution)

   ABSTRACT The rate of input of new genetic mutations, and the rate at which that variation is reshuffled, are key evolutionary processes shaping genomic diversity. Importantly, these rates vary not just across populations and species but also across individual genomes. Despite previous studies having demonstrated that failing to account for rate heterogeneity across the genome can bias the inference of both selective and neutral population genetic processes, mutation and recombination rate maps have to date only been generated for a relatively small number of organisms. Here, we infer such fine‐scale maps for the aye‐aye (Daubentonia madagascariensis)—a highly endangered strepsirrhine that represents one of the earliest splits in the primate clade and thus stands as an important outgroup to the more commonly studied haplorrhines—utilizing a recently released fully annotated genome combined with high‐quality population sequencing data. We compare our indirectly inferred rates to previous pedigree‐based estimates, finding further evidence of relatively low mutation and recombination rates in aye‐ayes compared to other primates. 

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5. Unprecedented female mutation bias in the aye-aye, a highly unusual lemur from Madagascar

   https://doi.org/10.1371/journal.pbio.3003015  

   Wang, Richard J; Peña-García, Yadira; Raveendran, Muthuswamy; Harris, R Alan; Nguyen, Thuy-Trang; Gingras, Marie-Claude; Wu, Yifan; Perez, Lesette; Yoder, Anne D; Simmons, Joe H; et al (February 2025, PLOS Biology)

   Hurst, Laurence D (Ed.)

   Every mammal studied to date has been found to have a male mutation bias: male parents transmit more de novo mutations to offspring than female parents, contributing increasingly more mutations with age. Although male-biased mutation has been studied for more than 75 years, its causes are still debated. One obstacle to understanding this pattern is its near universality—without variation in mutation bias, it is difficult to find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes (Daubentonia madagascariensis), a member of the strepsirrhine primates, and olive baboons (Papio anubis). In stark contrast to the pattern found across mammals, we find a much larger effect of maternal age than paternal age on mutation rates in the aye-aye. In addition, older aye-aye mothers transmit substantially more mutations than older fathers. We carry out both computational and experimental validation of our results, contrasting them with results from baboons and other primates using the same methodologies. Further, we analyze a set of DNA repair and replication genes to identify candidate mutations that may be responsible for the change in mutation bias observed in aye-ayes. Our results demonstrate that mutation bias is not an immutable trait, but rather one that can evolve between closely related species. Further work on aye-ayes (and possibly other lemuriform primates) should help to explain the molecular basis for sex-biased mutation. 

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