About

Rasmus Nielsen is a Professor of Integrative Biology, Statistics, and a member of the Center for Computational Biology at UC Berkeley. His research focuses on the statistical and computational aspects of evolutionary theory and genetics. A central problem in his work is understanding the molecular basis of evolutionary adaptation, specifically what occurs at the molecular level as one species transforms into another over evolutionary time. To investigate these questions, he has developed various computational methods and applied them to large-scale genomic data, including genomic comparisons of humans and chimpanzees. Nielsen has also contributed to the development of statistical methods in population genetics, medical genetics, phylogenetics, molecular ecology, and molecular evolution. His work aims to deepen the understanding of evolutionary processes through computational and statistical approaches, leveraging large genomic datasets to elucidate the mechanisms underlying adaptation and evolution.

Research topics

• Ecology
• Geography
• Demography
• Biology
• Archaeology

Selected publications

• Better Dynamic Balance as a Predictor of Better Horizontal Hop Performance: A Cross-Sectional Study

  International Journal of Sports Physical Therapy · 2026-05-01

  articleOpen access

  Background: Sports performance depends on multiple components, including strength, power, and balance. Both dynamic balance and hip muscle strength influence horizontal hop performance, but it remains unclear whether balance predicts hop performance differently across varying levels of hip strength. Purpose: The objectives of the present study were to i) investigate whether better dynamic balance was a predictor of better hop performance in Danish volunteers without musculoskeletal conditions, and ii) investigate whether this predictive association varies between groups with maximal isometric hip muscle strength below or above the sample mean in hip flexion, extension, abduction, and adduction. Study Design: Cross-Sectional Study. Methods: One hundred thirty-five healthy volunteers aged 18-50 years were recruited from the general population via personal networks, social media, and posters on various institutions and companies in Aarhus and Horsens, Denmark. Dynamic balance was assessed with the Y-Balance test measuring reach in the anterior, posteromedial, and posterolateral directions, summed to calculate a Composite Reach Distance. Horizontal forward hop performance was assessed using the Single-leg Hop for Distance test. Maximal isometric hip muscle strength of the flexors, extensors, abductors, and adductors was measured using a fixated dynamometer. All tests were performed on the right leg. A univariate linear regression model was used with regression coefficient as measure of association. To investigate differences in the slope of the linear regressions, participants were divided into groups based on whether their maximal isometric hip muscle strength was below or above the sample mean. Results: Better dynamic balance was associated with better horizontal hop performance (β = 0.59, [95% CI 0.29-0.88], p<0.001), similar associations were found for the posterior directions. This finding was consistent regardless of whether hip muscle strength was below or above the sample mean for all four directions (p>0.05). Conclusion: Individuals with better dynamic balance displayed better horizontal hop performance. These findings provide data on subjects without musculoskeletal conditions, which can be used as reference points when compared with symptomatic populations. Level of Evidence: 3b.

  PublisherDOI

• The genomic basis of adaptive leaf variation in the Galápagos giant daisies

  Nature Communications · 2026-04-16

  articleOpen access

  Scalesia (Asteraceae) is the largest endemic plant genus of the Galápagos archipelago and an example of adaptive radiation. While Scalesia species are highly varied in habit and morphology, most remarkable is their variety of leaf shapes, especially in the differential presence of leaf lobing/serration, a derived trait that evolved multiple times as a likely adaptation to the islands' hot and dry equatorial climate. Using population-level genomic data from 396 individuals representing all 15 recognized Scalesia species, we characterize this young radiation (around 1 million years ago), and reveal that their substantial morphological divergence and ecological specialization are primarily based on shared genetic variation. To further elucidate the repeated adaptive evolution of leaf lobing in Scalesia, we integrate genomic and leaf morphometric data, with transcriptomes from different developmental stages, and conclude that leaf lobing evolved through diversifying selection. Natural selection occurs independently on different regulators in the pathway controlling development of adaxial-abaxial leaf polarity, highlighting the importance of the founder populations' high genetic diversity maintained via allopolyploidy. Finally, our findings have implications for the conservation of Scalesia's threatened biodiversity, as unexpectedly high intra-specific genetic structure and long-term isolation among populations indicate widespread nascent speciation.

  PublisherDOI

• Acyl‐ <scp>CoA</scp> Binding Protein in White and Brown Adipose Tissue Is Dispensable for Systemic Energy Metabolism in Mice

  Acta Physiologica · 2026-01-11 · 1 citations

  articleOpen access

  AIM: Acyl-CoA binding protein plays a vital role in lipid metabolism by mediating the intracellular flux and utilization of long-chain acyl-CoAs. We generated an adipocyte-wide ACBP knockout mouse and a brown adipose tissue-specific ACBP knockout mouse to investigate ACBP function in adipose tissue. METHODS: mice with transgenic mice expressing Cre recombinase under the control of the adiponectin (Adipoq-Cre) or uncoupling protein 1 (Ucp1-Cre) promoter, respectively. Systemic energy expenditure was assessed by indirect calorimetry. Body composition was examined using nuclear magnetic resonance. Primary brown and white preadipocytes were isolated to examine their ability to differentiate to mature adipocytes. Lipid composition of adipose tissues was examined by lipidomics. Global changes in gene expression in adipose tissues were examined by RNA sequencing. Tissue respiration was determined using high-resolution respirometry. RESULTS: We demonstrate that loss of ACBP in adipose tissue does not affect body weight, fat and lean mass, food intake and systemic energy expenditure, even under cold stress. Global gene expression analysis shows only minor changes in gene expression, whereas lipidomic profiling reveals a subtle increase in acyl-carnitine levels in brown adipose tissue. Lipolytic activity in white adipose tissue as well as plasma glycerol, nonesterified fatty acid and triacylglycerol levels remained unaffected. In addition, no changes in mitochondrial respiration in BAT were observed. CONCLUSION: Our findings suggest that ACBP is dispensable for adipose tissue function and systemic energy metabolism.

  PublisherOA PDFDOI

• The genetics, evolution, and maintenance of a biological rock-paper-scissors game

  Science · 2026-01-01 · 5 citations

  articleSenior author

  ) play a biological rock-paper-scissors game in which three differently colored male morphs utilize alternative mating strategies. We identified the genetic basis of this polymorphism, which was previously posited to arise from three alleles at one locus. Orange usurper and blue mate-guarder morphs are associated with two divergent haplotypes in the regulatory region of the sepiapterin reductase gene, but yellow sneaker morphs appear to arise through phenotypic plasticity from the same genetic background as blue morphs. Our simulations show that rock-paper-scissors dynamics can better maintain a polymorphism with a genetic system of two alleles plus plasticity than with a three-allele system. This form of balancing selection that combines genetic determination with phenotypic plasticity expands the possibilities for how stable polymorphisms arise in nature.

  PublisherDOI

• Author Correction: Robust and accurate Bayesian inference of genome-wide genealogies for hundreds of genomes

  Nature Genetics · 2025-10-10

  erratumOpen access

  In the version of this article originally published, there were labeling errors in several figures.In Fig. 2a, b, in the y-axis label now reading "Inferred pairwise TMRCA (generations)," the word "generations" was missing, while in the right-hand panel of Fig. 2a, the m.s.e.value now reading "0.78" appeared originally as "078."In Fig. 3a, panel headers "SINGER; Relate; tsinfer+tsdate" were missing.The color keys in Fig. 4a were all mistakenly labeled "SINGER 90% CI" and now specify the ARGweaver and Relate methods.In Extended Data Fig. 3b, panel headers for the SINGER and ARGweaver plots were missing.

  PublisherOA PDFDOI

• A general framework for branch length estimation in Ancestral Recombination Graphs

  Proceedings of the National Academy of Sciences · 2025-11-25 · 1 citations

  articleOpen accessSenior authorCorresponding

  Inference of Ancestral Recombination Graphs (ARGs) is of central interest in the analysis of genomic variation. ARGs can be specified in terms of topologies and coalescence times. The coalescence times are usually estimated using an informative prior derived from coalescent theory, but this may generate biased estimates and can also complicate downstream inferences based on ARGs. Here, we introduce, Prior-Oblivious Length Estimation in Genealogies with Oriented Networks (POLEGON), an approach for estimating branch lengths for ARGs which uses an uninformative prior. Using extensive simulations, we show that this method provides improved estimates of coalescence times and leads to more accurate inferences of effective population sizes under a wide range of demographic assumptions (population expansion, bottleneck, split, etc.). It also improves other downstream inferences including estimates of mutation rates. We apply the method to data from the 1000 Genomes Project to investigate population size histories and differential mutation signatures across populations. We also estimate coalescence times in the Human Leukocyte Antigen (HLA) region and show that they exceed 30 My in multiple segments.

  PublisherOA PDFDOI

• vcfgl: a flexible genotype likelihood simulator for VCF/BCF files

  Bioinformatics · 2025-03-05 · 4 citations

  articleOpen access

  MOTIVATION: Accurate quantification of genotype uncertainty is pivotal in ensuring the reliability of genetic inferences drawn from NGS data. Genotype uncertainty is typically modeled using Genotype Likelihoods (GLs), which can help propagate measures of statistical uncertainty in base calls to downstream analyses. However, the effects of errors and biases in the estimation of GLs, introduced by biases in the original base call quality scores or the discretization of quality scores, as well as the choice of the GL model, remain under-explored. RESULTS: We present vcfgl, a versatile tool for simulating genotype likelihoods associated with simulated read data. It offers a framework for researchers to simulate and investigate the uncertainties and biases associated with the quantification of uncertainty, thereby facilitating a deeper understanding of their impacts on downstream analytical methods. Through simulations, we demonstrate the utility of vcfgl in benchmarking GL-based methods. The program can calculate GLs using various widely used genotype likelihood models and can simulate the errors in quality scores using a Beta distribution. It is compatible with modern simulators such as msprime and SLiM, and can output data in pileup, Variant Call Format (VCF)/BCF, and genomic VCF file formats, supporting a wide range of applications. The vcfgl program is freely available as an efficient and user-friendly software written in C/C++. AVAILABILITY AND IMPLEMENTATION: vcfgl is freely available at https://github.com/isinaltinkaya/vcfgl.

  PublisherOA PDFDOI

• Occurrence of aneuploidy across the range of coast redwood ( <i>Sequoia sempervirens</i> )

  G3 Genes Genomes Genetics · 2025-03-25 · 1 citations

  articleOpen accessSenior author

  Aneuploidy, a condition characterized by an abnormal number of chromosomes, can have significant consequences for fitness of an organism, often manifesting in reduced fertility and other developmental challenges. In plants, aneuploidy is particularly complex to study, especially in polyploid species such as coast redwood (Sequoia sempervirens (D. Don) Endl.), which is a hexaploid conifer (2n=6×=66). This study leverages a novel Markov Chain Monte Carlo method based on sequence depth to investigate the occurrence of aneuploidy across the range of coast redwood. We show that aneuploidy, defined here as a whole-chromosome gain or loss, is prevalent in second-growth redwoods, predominantly as additional chromosomes, while vegetatively propagated plants frequently experience chromosome loss. Although our study does not directly assess the fitness of aneuploids, the frequency of chromosomal instability observed in vegetatively propagated plants compared to second-growth and old-growth trees raises questions about their long-term developmental viability and potential to become established trees. These findings have significant implications for redwood conservation and restoration strategies, especially as methods such as tissue culture propagation becomes the primary mode of producing nursery stock plants used in reforestation.

  PublisherOA PDFDOI

• ASTER: A Package for Large-Scale Phylogenomic Reconstructions

  Molecular Biology and Evolution · 2025-07-16 · 35 citations

  articleOpen access

  Many algorithms are available for inferring species trees from various input types while accounting for gene tree discordance. Several quartet-based species tree inference methods, collectively known as the ASTRAL family, are based on similar ideas and are in wide use. Here, we integrate all ASTRAL-like methods into a single package called ASTER, comprising several tools, each designed for a different input type: (i) ASTRAL for single-copy gene tree topologies, (ii) weighted ASTRAL (wASTRAL) for single-copy gene tees with branch length and/or support, (iii) ASTRAL-Pro for multi-copy gene tree topologies, (iv) CASTER for multiple sequence alignments, including genome alignments, and (v) WASTER for short-reads and assembled genomes. These tools collectively enhance the scalability, accuracy, and versatility of species tree inference.

  PublisherOA PDFDOI

• Robust and accurate Bayesian inference of genome-wide genealogies for hundreds of genomes

  Nature Genetics · 2025-09-01 · 15 citations

  articleOpen access

  The Ancestral Recombination Graph (ARG), which describes the genealogical history of a sample of genomes, is a vital tool in population genomics and biomedical research. Recent advancements have substantially increased ARG reconstruction scalability, but they rely on approximations that can reduce accuracy, especially under model misspecification. Moreover, they reconstruct only a single ARG topology and cannot quantify the considerable uncertainty associated with ARG inferences. Here, to address these challenges, we introduce SINGER (sampling and inferring of genealogies with recombination), a method that accelerates ARG sampling from the posterior distribution by two orders of magnitude, enabling accurate inference and uncertainty quantification for hundreds of whole-genome sequences. Through extensive simulations, we demonstrate SINGER's enhanced accuracy and robustness to model misspecification compared to existing methods. We demonstrate the utility of SINGER by applying it to individuals of British and African descent within the 1000 Genomes Project, identifying signals of population differentiation, archaic introgression and strong support for ancient polymorphism in the human leukocyte antigen region shared across primates.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM116044

  NIH · $2.4M · 2021

• Berkeley Training Program in Genomics and Computational Biology

  NIH · $12.6M · 2000–2030

• NIH Grant R01HG003229

  NIH · $4.0M · 2014

• Enabling Precision Genomics Using Adaptive Variation

  NIH · $435k · 2020–2024

• NIH Grant R01MH084695

  NIH · $1.1M · 2012

Frequent coauthors

• Eske Willerslev

  University of Cambridge

  317 shared

• Thorfinn Sand Korneliussen

  University of Copenhagen

  178 shared

• Morten E. Allentoft

  146 shared

• J. Víctor Moreno-Mayar

  University of Lausanne

  141 shared

• Martin Sikora

  University of Copenhagen

  135 shared

• Ludovic Orlando

  Université Toulouse III - Paul Sabatier

  118 shared

• Jun Wang

  Chinese Academy of Sciences

  102 shared

• Andrés Ingason

  Lundbeck Foundation

  93 shared

Labs

• Center for Computational BiologyPI