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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. 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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3. 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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4. A whole-genome scan for evidence of recent positive and balancing selection in aye-ayes (Daubentonia madagascariensis) utilizing a well-fit evolutionary baseline model

   https://doi.org/10.1101/2024.11.08.622667  

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

   The aye-aye (Daubentonia madagascariensis) is one of the 25 most endangered primate species in the world, maintaining amongst the lowest genetic diversity of any primate measured to date. Characterizing patterns of genetic variation within aye-aye populations, and the relative influences of neutral and selective processes in shaping that variation, is thus important for future conservation efforts. In this study, we performed the first whole-genome scans for recent positive and balancing selection in the species, utilizing high-coverage population genomic data from newly sequenced individuals. We generated null thresholds for our genomic scans by creating an evolutionarily appropriate baseline model that incorporates the demographic history of this aye-aye population, and identified a small number of candidate genes. Most notably, a suite of genes involved in olfaction — a key trait in these nocturnal primates — were identified as experiencing long-term balancing selection. We also conducted analyses to quantify the expected statistical power to detect positive and balancing selection in this population using site frequency spectrum-based inference methods, once accounting for the potentially confounding contributions of population history, recombination and mutation rate variation, and purifying and background selection. This work, presenting the first high-quality, genome-wide polymorphism data across the functional regions of the aye-aye genome, thus provides important insights into the landscape of episodic selective forces in this highly endangered species. 

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5. Estimating the distribution of fitness effects in aye-ayes (Daubentonia madagascariensis), accounting for population history as well as mutation and recombination rate heterogeneity

   https://doi.org/10.1101/2025.01.02.631144  

   Soni, Vivak; Versoza, Cyril J; Pfeifer, Susanne P; Jensen, Jeffrey D (January 2025, bioRxiv)

   The distribution of fitness effects (DFE) characterizes the range of selection coefficients from which new mutations are sampled, and thus holds a fundamentally important role in evolutionary genomics. To date, DFE inference in primates has been largely restricted to haplorrhines, with limited data availability leaving the other suborder of primates, strepsirrhines, largely under-explored. To advance our understanding of the population genetics of this important taxonomic group, we here map exonic divergence in aye-ayes (Daubentonia madagascariensis) – the only extant member of the Daubentoniidae family of the Strepsirrhini suborder. We further infer the DFE in this highly-endangered species, utilizing a recently published high-quality annotated reference genome, a well-supported model of demographic history, as well as both direct and indirect estimates of underlying mutation and recombination rates. The inferred distribution is generally characterized by a greater proportion of deleterious mutations relative to humans, providing evidence of a larger long-term effective population size. In addition however, both immune-related and sensory-related genes were found to be amongst the most rapidly evolving in the aye-aye genome. 

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