skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on February 7, 2026

Title: Unprecedented female mutation bias in the aye-aye, a highly unusual lemur from Madagascar
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.  more » « less
Award ID(s):
2314898
PAR ID:
10617878
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ;
Editor(s):
Hurst, Laurence D
Publisher / Repository:
PLOS Biology
Date Published:
Journal Name:
PLOS Biology
Volume:
23
Issue:
2
ISSN:
1545-7885
Page Range / eLocation ID:
e3003015
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. 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. 
    more » « less
  2. 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 » « less
  3. 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 » « less
  4. 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. 
    more » « less
  5. Aye-ayes (Daubentonia madagascariensis) are one of the 25 most critically endangered primate species in the world. Endemic to Madagascar, their small and highly fragmented populations make them particularly vulnerable to both genetic disease and anthropogenic environmental changes. Over the past decade, conservation genomic efforts have largely focused on inferring and monitoring population structure based on single nucleotide variants to identify and protect critical areas of genetic diversity. However, the recent release of a highly contiguous genome assembly allows, for the first time, for the study of structural genomic variation (deletions, duplications, insertions, and inversions) which are likely to impact a substantial proportion of the species’ genome. Based on whole-genome, short-read sequencing data from 14 individuals, >1,000 high-confidence autosomal structural variants were detected, affecting ∼240 kb of the aye-aye genome. The majority of these variants (>85%) were deletions shorter than 200 bp, consistent with the notion that longer structural mutations are often associated with strongly deleterious fitness effects. For example, two deletions longer than 850 bp located within disease-linked genes were predicted to impose substantial fitness deficits owing to a resulting frameshift and gene fusion, respectively; whereas several other major effect variants outside of coding regions are likely to impact gene regulatory landscapes. Taken together, this first glimpse into the landscape of structural variation in aye-ayes will enable future opportunities to advance our understanding of the traits impacting the fitness of this endangered species, as well as allow for enhanced evolutionary comparisons across the full primate clade. 
    more » « less