Biology subjects

Pfeifer, S. P.

Publications and source records attributed to Pfeifer, S. P..

At least 19 recordsLinked to original sources

bioRxiv2026

Inferring the relative contributions of evolutionary processes shaping X chromosome dynamics in the common marmoset (Callithrix jacchus) in the presence of twinning and hematopoietic chimerism

The common marmoset (Callithrix jacchus) is a biomedically important species that is characterized by two unusual biological traits -- a high frequency of twin births and hematopoietic chimerism -- that preclude the application of many commonly used population genomic approaches for quantifying evolutionary processes. In this study, we directly account for both factors in order to estimate fine-scale mutation and recombination rate maps, as well as to infer the demographic and selective processes shaping variation, on the common marmoset X chromosome. Comparing our findings to estimates recently inferred on the autosomes of this species, we find reduced rates of mutation and recombination on the X, as expected. Furthermore, population sex ratios are inferred to be nearly equal, and the appropriately rescaled autosomal population history fits the X chromosome well. Finally, we report evidence of recent selective sweeps targeting a number of X-linked genes, including several of significant biomedical relevance. Overall, these analyses provide novel insights into the evolutionary processes shaping X chromosome evolution in this biomedically-relevant primate model.

evolutionary biology↗

bioRxiv2026

Evolutionary genomics based on PacBio HiFi long-read sequencing data reveals the importance of structural variants in shaping population-specific differences between Chinese and Indian rhesus macaques (Macaca mulatta)

Rhesus macaques (Macaca mulatta) are the most widely used non-human primate model for translational research relevant to human health and disease. Although several genetically distinct populations have been recognized across the species extensive habitat range in Asia, the majority of biomedical studies in the United States and abroad focuses on individuals of either Chinese or Indian descent. Notably, phenotypic differences exist between these two populations which can influence biomedical research outcomes; however, the genetic basis and molecular mechanisms underlying these differences are generally not well understood. Based on novel PacBio HiFi long-read sequencing data from 20 rhesus macaques -- ten of Chinese origin and ten of Indian origin -- we here characterize the genome-wide landscape of structural variation in these two biomedically-relevant populations. Our results highlight differences in the structural variant landscape affecting genes involved in neural communication and signaling pathways, in line with the known differences in temperament between the two populations. Furthermore, while the majority of discovered structural variants were located in intergenic and non-coding regions of the genome, 15 of the discovered population-specific structural variants were predicted to exhibit a high functional effect on genes associated with human disease, indicating that they may play an important role in shaping the differences in disease susceptibility between the populations. Taken together, by providing detailed insights into population-specific structural variation, this genomic resource will aid the design and interpretation of future studies aiming to link genotype, phenotype, and fitness in the context of human health and disease, and facilitate broader comparative analyses of structural variation as a force shaping genome evolution across primates.

evolutionary biology↗

bioRxiv2026

Inferring the demographic history of Chinese and Indian rhesus macaque (Macaca mulatta) populations from PacBio HiFi long-read sequencing data

The rhesus macaque (Macaca mulatta) is one of the most widely used animal models in biomedical research, both as it resembles humans in key biological aspects and as it is characterized by a broad geographic range. Most of the individuals housed in U.S. research colonies have been sampled from either China or India, though notably the source population of these animals has significantly shifted over time. Given the substantial genetic and immunological differences between these populations, a deeper understanding of the underlying population structure is critically important for biomedical interpretation. Despite this, the demographic histories of these two populations remain poorly resolved. Here, we present an analysis of whole-genome, PacBio HiFi long-read sequencing data from ten unrelated individuals of each population, applying four related model- and non-model based demographic inference approaches, in order to reconstruct their ancestral history. We evaluated the fit of the subsequently estimated models against the empirical data, and incorporated underlying uncertainty in the mutation rates used for scaling. We inferred a well-fitting population history characterized by substantial structure between Chinese and Indian populations, with a split time [~]140,000 generations ago from an ancestral population of [~]65,000 individuals. We additionally inferred the subsequent history of size change within, and gene flow between, these populations, reaching the current estimated sizes of [~]220,000 individuals in the Chinese population and [~]14,000 individuals in the Indian population. The robust baseline demographic model established in this study will serve as a valuable resource for future research on this species, including for improved fine-scale recombination mapping, selection inference, and association studies.

evolutionary biology↗

bioRxiv2026

Comparing fine-scale mutation and recombination landscapes in rhesus macaque (Macaca mulatta) populations of Chinese and Indian descent inferred from both short- and long-read sequencing data

Genomic diversity amongst primates is fundamentally shaped by species- and population-specific rates of mutation and recombination. In this study, we infer fine-scale mutation and recombination rate maps for the rhesus macaque (Macaca mulatta) -- the most widely used non-human primate model in biomedical research -- leveraging both short-(Illumina) and long-(PacBio HiFi) read sequencing data from two distinct populations of Chinese and Indian descent. Thereby, we draw comparisons between the rates estimated from each dataset, highlighting both biologically meaningful variation between these populations as well as artefactual discrepancies likely arising from systematic biases and differences in the utilized sequencing technologies. Consistent with previous observations in humans, broad-scale features of the recombination landscape are well-conserved between the two populations, but significant differences exist at the finer scales. Notably, we find evidence for a high rate of turnover in recombination hotspots over a short evolutionary time span, resulting in population-specific recombination maps in which the vast majority of the >30,000 identified recombination hotspots in one population are inactive in the other population. Given that mutation and recombination rates are necessary components for the interpretation of other diversity-shaping processes and events, including those characterizing both the underlying demographic and selective histories, the incorporation of these population-specific maps into future models will improve our understanding of the evolutionary genomics of the species. Additionally, these maps will serve as a fundamental component of future genome-wide association and fine-mapping studies of disease traits in this biomedical model system.

evolutionary biology↗

bioRxiv2026

Inferring patterns of purifying, positive and balancing selection in the coppery titi monkey (Plecturocebus cupreus) utilizing a well-fit evolutionary baseline model

Despite the coppery titi monkey (Plecturocebus cupreus) being a model system for the study of neurodevelopment and behavior, the evolutionary forces shaping observed levels and patterns of genetic variation in the species have remained poorly studied. In order to illuminate the pervasive eCects of purifying and background selection, we have fit a distribution of fitness eCects of newly arising exonic mutations, utilizing patterns of polymorphism and divergence based on a recently published high-quality genome assembly. To further characterize episodically acting selective processes, we additionally performed the first whole-genome scans for recent positive and balancing selection in this species, reducing false-positive rates by incorporating the demographic history of the population into an evolutionary null model. These scans identified a small number of biomedically-relevant genes with strong statistical support for having experienced recent selective sweeps or long-term balancing selection. In addition, we identified four genomic deletions bearing the signatures of balancing selection. Taken together, this study provides the first insights into patterns of persistent and episodic selective processes in this species.

evolutionary biology↗

bioRxiv2026

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

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 computational de novo mutation detection pipeline based on pan-genome graphs, has provided a detailed picture of the sex-averaged mutation rate -- 0.63 x 10-8 (95% CI: 0.43 x 10-8 - 0.90 x 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.

evolutionary biology↗

bioRxiv2026

The landscape of structural variation in coppery titi monkeys (Plecturocebus cupreus)

Coppery titi monkeys (Plecturocebus cupreus) are an important non-human primate model for studying neurobiology and social behavior, in part owing to their relatively unusual combination of social monogamy and paternal care. Despite this importance, relatively little is known regarding the underlying population genomics of this platyrrhine. This study presents high-coverage, whole-genome sequencing data from 26 individuals which, combined with a highly accurate multi-algorithm ensemble approach, was used to characterize the first map of structural variation in the species. This novel genomic resource includes over 13,000 structural variants, with the majority (>90%) being copy number variants. While many of these were found to be located in intergenic regions, several affected genes associated with disease, including an inversion predicted to impact a pathway implicated in early-onset Parkinsons disease. Furthermore, utilizing parent-offspring trios included within this study, the de novo structural variant rate was estimated to be one in every 1.5 births, similar to that reported in rhesus macaques but considerably higher than that observed in large human cohorts, as may be expected from underlying differences in life history traits amongst these species. Taken together, these insights into the structural variant landscape of P. cupreus will not only improve their utility as a behavioral model system, but will also contribute to our general understanding of the role of structural variation in both the evolution of the primate clade and disease-outcomes.

evolutionary biology↗

bioRxiv2026

Inferring fine-scale rates of mutation and recombination in the coppery titi monkey (Plecturocebus cupreus)

Despite being a primate of considerable biomedical interest, particularly as a model for social behavior and neurobiology, the evolutionary processes shaping genetic variation in the coppery titi monkey (Plecturocebus cupreus) remain largely uncharacterized. Utilizing divergence and polymorphism data together with a recently published high-quality, annotated genome, we here infer the first fine-scale maps of mutation and recombination rates in this platyrrhine. We find a mean genome-wide mutation rate of between 0.93 x 10-8 and 1.61 x 10-8 per site per generation and a mean genome-wide recombination rate of 0.975 cM/Mb, in line with fine-scale rates estimated in other primates. In addition to providing novel biological insights into the mutation and recombination rates in this emerging model species for behavioral research, these fine-scale maps also improve our understanding of how the processes of mutation and recombination shape genetic variation in the coppery titi monkey genome, and their incorporation into evolutionary models will be a necessary aspect of future downstream inference of other evolutionary processes required to elucidate the genetic factors underlying the phenotypic traits studied in this species.

evolutionary biology↗

bioRxiv2026

Sex-specific landscapes of crossover and non-crossover recombination in coppery titi monkeys (Plecturocebus cupreus)

Along with germline mutations, meiotic recombination plays a fundamental role in shaping genetic diversity and thus directly influences a species potential adaptive response to environmental change, amongst other features. Despite the recombination landscape being of central importance for a variety of questions in molecular evolution, the genome-wide distribution and frequency of recombination remains to be elucidated in many non-human primate species. Utilizing novel high-coverage genomic data from three multi-sibling families, we here provide the first estimates of the rates and patterns of crossover and non-crossover recombination in coppery titi monkeys (Plecturocebus cupreus) -- a socially monogamous, pair-bonded primate that serves as an important model in behavioral research. Consistent with haplorrhines, crossover and non-crossover recombination in this platyrrhine are frequently localized at PRDM9-mediated hotspots, characterized by a 15-mer binding motif with substantial similarities to the degenerate 13-mer motif found in humans. The sex-averaged crossover rate in coppery titi monkeys is comparable with those of other primates; however, no significant difference in recombination rates was observed between the sexes, despite a pronounced maternal age effect in the species. Similarities also exist with regards to the sex-specific genomic distribution of non-crossover events, though the minimal conversion tract lengths of extended events was observed to be considerably longer in maternally-inherited non-crossovers. Taken together, these similarities and differences in the recombination landscape relative to other primates highlight the importance of incorporating species-specific rates and patterns in evolutionary models, and the resources provided here will thus serve to aid future studies in this important primate model system.

evolutionary biology↗

bioRxiv2026

Inferring the demographic history of coppery titi monkeys (Plecturocebus cupreus) from high-quality, whole-genome, population-level data

Despite being an important biomedical model species for social behavior, the natural population history of the coppery titi monkey (Plecturocebus cupreus) remains largely uncharacterized, in part due to the scarcity of genomic resources available for the species. Apart from the inherent interest in the demographic dynamics of this abundant platyrrhine native to the Amazon forest of Brazil and Peru, this quantification will also serve as a central component of future genotype-to-phenotype studies, given the ability of historical population size change and structure to generate genetic associations. In this study, we deep-sequenced the genomes of six unrelated individuals and inferred a baseline demographic model based on observed levels and patterns of variation in the non-coding regions of the genome. In characterizing these demographic dynamics, we found that estimated population size changes correspond well to previously described speciation times as well as to large-scale climatic changes relating to glaciation patterns.

evolutionary biology↗

bioRxiv2025

Investigating the effects of chimerism on the inference of selection: quantifying genomic targets of purifying, positive, and balancing selection in common marmosets (Callithrix jacchus)

The common marmoset (Callithrix jacchus) is of considerable biomedical importance, yet there remains a need to characterize the evolutionary forces shaping empirically observed patterns of genomic variation in the species. However, two uncommon biological traits potentially prevent the use of standard population genetic approaches in this primate: a high frequency of twin-births and the prevalence of hematopoietic chimerism. Here we characterize the impact of these biological features on the inference of natural selection, and directly model twinning and chimerism when performing inference of the distribution of fitness effects to characterize general selective dynamics as well as when scanning the genome for loci shaped by the action of episodic positive and balancing selection. Results suggest a generally increased degree of purifying selection relative to human populations, consistent with the larger estimated effective population size of common marmosets. Furthermore, genomic scans based on an appropriate evolutionary baseline model reveal a small number of genes related to immunity, sensory perception, and reproduction to be strong sweep candidates. Notably, two genes in the major histocompatibility complex were found to have strong evidence of being maintained by balancing selection, in agreement with observations in other primate species. Taken together, this work, presenting the first whole-genome characterization of selective dynamics in the common marmoset, thus provides important insights into the landscape of both persistent and episodic selective forces in this species.

evolutionary biology↗

bioRxiv2025

Inferring the landscapes of mutation and recombination in the common marmoset (Callithrix jacchus) in the presence of twinning and hematopoietic chimerism

The common marmoset (Callithrix jacchus) is an important model in biomedical and clinical research, particularly for the study of age-related, neurodegenerative, and neurodevelopmental disorders (due to their biological similarities with humans), infectious disease (due to their susceptibility to a variety of pathogens), as well as developmental biology (due to their short gestation period relative to many other primates). Yet, while being one of the most commonly used non-human primate models for research, the population genomics of the common marmoset remains relatively poorly characterized, despite the critical importance of this knowledge in many areas of research including genome-wide association studies, models of polygenic risk scores, and scans for the targets of selection. This neglect owes, at least in part, to two biological peculiarities related to the reproductive mode of the species -- frequent twinning and sibling chimerism -- which are likely to affect standard population genetic approaches relying on assumptions underlying the Wright-Fisher model. Using high-quality population genomic data, we here infer the rates and landscapes of mutation and recombination -- two fundamental processes dictating the levels and patterns of genetic variability -- in the presence of these biological features, and discuss our findings in light of recent work in primates. Our results suggest that, while the species exhibits relatively low neutral mutation rates, rates of recombination are in the range of those observed in other anthropoids. Moreover, the recombination landscape of common marmosets, like that of many vertebrates, is dominated by PRDM9-mediated hotspots, with artificial intelligence-based models predicting an intricate 3D-structure of the species-specific PRDM9-DNA binding complex in silico. Apart from providing novel insights into the population genetics of common marmosets, given the importance of the availability of fine-scale maps of mutation and recombination for evolutionary inference, this work will also serve as a valuable resource to aid future genomic research in this widely studied system.

evolutionary biology↗

bioRxiv2025

Accounting for chimerism in demographic inference: reconstructing the history of common marmosets (Callithrix jacchus) from high-quality, whole-genome, population-level data

As a species of considerable biomedical importance, characterizing the evolutionary genomics of the common marmoset (Callithrix jacchus) is of significance across multiple fields of research. However, at least two peculiarities of this species potentially preclude commonly utilized population genetic modeling and inference approaches: a high frequency of twin births and hematopoietic chimerism. We here investigate these effects within the context of demographic inference, demonstrating via simulation that neglecting these biological features results in significant mis-inference of the underlying population history. Based upon this result, we develop a novel approximate Bayesian inference approach accounting for both common twin-births as well as chimeric sampling. In addition, we present novel population genomic data from 15 individuals sequenced to high-coverage, and utilize gene-level annotations to identify neutrally evolving intergenic regions appropriate for demographic inference. Applying our developed methodology, we estimate a well-fitting population history for this species, which suggests robust ancestral and current population sizes, as well as a size reduction roughly 7,000 years ago likely associated with a shift from arboreal to savanna vegetation in north-eastern Brazil during this period.

evolutionary biology↗

bioRxiv2025

Interpreting patterns of X chromosomal relative to autosomal diversity in aye-ayes(Daubentonia madagascariensis)

We here present high-quality, population-level sequencing data from the X chromosome of the highly-endangered aye-aye, Daubentonia madagascariensis. Using both polymorphism- and divergence-based inference approaches, we quantify fine-scale mutation and recombination rate maps, study the demographic and selective processes additionally shaping variation on the X chromosome, and compare these estimates to those recently inferred from the autosomes in this species. Results suggest that an equal sex ratio is most consistent with observed patterns of variation, and that no sex-specific demographic patterns are needed to fit the empirical site frequency spectrum. Further, reduced rates of recombination were observed relative to the autosomes as would be expected, whereas mutation rates were inferred to be similar. Utilizing the estimated population history together with the mutation and recombination rate maps, we evaluated evidence for both recent and recurrent selective sweeps as well as balancing selection across the X chromosome, finding no significant evidence supporting the action of these episodic processes. Overall, these analyses provide new insights into the evolution of the X chromosome in this species, which represents one of the earliest splits in the primate clade.

evolutionary biology↗

bioRxiv2025

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

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.

evolutionary biology↗

bioRxiv2024

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

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.

evolutionary biology↗

bioRxiv2024

Inferring the demographic history of aye-ayes (Daubentonia madagascariensis) from high-quality, whole-genome, population-level data

The nocturnal aye-aye, Daubentonia madagascariensis, is one of the most elusive lemurs on the island of Madagascar. The timing of its activity and arboreal lifestyle has generally made it difficult to obtain accurate assessments of population size using traditional census methods. Therefore, alternative estimates provided by population genetic inference are essential for yielding much needed information for conservation measures and for enabling ecological and evolutionary studies of this species. Here, we utilize genomic data from 17 unrelated individuals -- including 5 newly sequenced, high-coverage genomes -- to estimate this history. Essential to this estimation are recently published annotations of the aye-aye genome which allow for variation at putatively neutral genomic regions to be included in the estimation procedures, and regions subject to selective constraints, or in linkage to such sites, to be excluded owing to the biasing effects of selection on demographic inference. By comparing a variety of demographic estimation tools to develop a well-supported model of population history, we find strong support for the species to consist of two demes, separating northern Madagascar from the rest of the island. Additionally, we find that the aye-aye has experienced two severe reductions in population size. The first occurred rapidly, approximately 3,000 to 5,000 years ago, and likely corresponded with the arrival of humans to Madagascar. The second occurred over the past few decades and is likely related to substantial habitat loss, suggesting that the species is still undergoing population decline and remains at great risk for extinction.

evolutionary biology↗

bioRxiv2024

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

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.

evolutionary biology↗