About

Manyuan Long is the Edna K. Papazian Distinguished Service Professor of Ecology and Evolution at The University of Chicago. Since his doctoral studies in California in the early 1990s, he has focused on understanding how genes originate and evolve, employing theoretical, computational, and molecular experimental approaches. His research explores the phenotypic effects and functions of new genes, their role in development, gene interactions, sexual selection, and de novo gene origination. Long has contributed significantly to the field of molecular evolution and genetics, particularly in the area of new gene evolution, and has authored approximately 200 publications, including research reports, reviews, commentaries, and popular science articles. His work has helped shape major textbooks in evolutionary biology and has been highlighted in prominent media outlets. Recognized for his scientific impact, he received the John Simon Guggenheim Memorial Fellowship in 2022 and was named an AAAS Fellow in 2014 for his distinguished contributions to molecular evolution and genetics. His research has also influenced societal debates and legal cases, and he has been active in public science communication through interviews and media coverage.

Research topics

• Genetics
• Computational biology
• Biology
• Evolutionary biology
• Astronomy
• Ecology

Selected publications

• Functional innovation through new genes as a general evolutionary process

  Nature Genetics · 2025-01-28 · 34 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection

  Genome Research · 2025-02-14 · 4 citations

  articleOpen accessSenior author

  New genes (or young genes) are genetic novelties pivotal in mammalian evolution. However, their phenotypic impacts and evolutionary patterns over time remain elusive in humans owing to the technical and ethical complexities of functional studies. Integrating gene age dating with Mendelian disease phenotyping, we reveal a gradual rise in disease gene proportion as gene age increases. Logistic regression modeling indicates that this increase in older genes may be related to their longer sequence lengths and higher burdens of deleterious de novo germline variants (DNVs). We also find a steady integration of new genes with biomedical phenotypes into the human genome over macroevolutionary timescales (∼0.07% per million years). Despite this stable pace, we observe distinct patterns in phenotypic enrichment, pleiotropy, and selective pressures across gene ages. Young genes show significant enrichment in diseases related to the male reproductive system, indicating strong sexual selection. Young genes also exhibit disease-related functions potentially linked to human phenotypic innovations, such as increased brain size, musculoskeletal phenotypes, and color vision. We further reveal a logistic growth pattern of pleiotropy over evolutionary time, indicating a diminishing marginal growth of new functions for older genes owing to intensifying selective constraints over time. We propose a "pleiotropy-barrier" model that delineates higher potential for phenotypic innovation in young genes compared to older genes, a process under natural selection. Our study demonstrates that evolutionarily new genes are critical in influencing human reproductive evolution and adaptive phenotypic innovations driven by sexual and natural selection, with low pleiotropy as a selective advantage.

  PublisherOA PDFDOI

• Publisher Correction: Functional innovation through new genes as a general evolutionary process

  Nature Genetics · 2025-02-07

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• Subcellular Enrichment Patterns of New Genes in <i>Drosophila</i> Evolution

  Molecular Biology and Evolution · 2025-02-01 · 4 citations

  articleOpen accessSenior author

  The evolutionary patterns of proteins within subcellular compartments underlie the innovation and diversification foundation of the living eukaryotic organism. The location of proteins in subcellular compartments promotes the formation of network interaction modules, which in turn reshape the architecture of higher-level protein-protein interaction networks. Here, we conducted the most up-to-date gene age dating of Drosophila melanogaster by employing recently available long-read sequencing genomes as references. We found that an elevated gene fixation in the most recent common ancestor of Drosophila genus predated the divergence between two Drosophila subgenera, and a significant tendency of these genes in D. melanogaster encode proteins that localize to the extracellular matrix, accompanying the adaptive radiation of Drosophila species. Proteins encoded by genes located in the extracellular space exhibit higher sequence divergence, suggesting a rapid evolutionary process. We also observed that proteins encoded by genes originating from the same evolutionary branches tend to co-localize in the same subcellular compartments, and proteins in the same subcellular compartment tend to interact with each other. The proteins encoded by genes that have persisted through deeper branches exhibit broader localization across multiple subcellular compartments, enhancing the likelihood of their integration into various protein or gene regulatory networks, thereby increasing functional diversity. These evolutionary patterns not only contribute to understanding the evolution of subcellular localization in proteins encoded by genes originating from different branches, but also provide insights into the evolution of protein-protein networks driven by the emergence of new genes.

  PublisherDOI

• Bryophytes hold a larger gene family space than vascular plants

  Nature Genetics · 2025-09-22 · 26 citations

  articleOpen access

  After 500 million years of evolution, extant land plants compose the following two sister groups: the bryophytes and the vascular plants. Despite their small size and simple structure, bryophytes thrive in a wide variety of habitats, including extreme conditions. However, the genetic basis for their ecological adaptability and long-term survival is not well understood. A comprehensive super-pangenome analysis, incorporating 123 newly sequenced bryophyte genomes, reveals that bryophytes possess a substantially greater diversity of gene families than vascular plants. This includes a higher number of unique and lineage-specific gene families, originating from extensive new gene formation and continuous horizontal transfer of microbial genes over their long evolutionary history. The evolution of bryophytes' rich and diverse genetic toolkit, which includes new physiological innovations like unique immune receptors, likely facilitated their spread across different biomes. These newly sequenced bryophyte genomes offer a valuable resource for exploring alternative evolutionary strategies for terrestrial success.

  PublisherDOI

• Sex-biased duplicates are rapidly generated during <i>Drosophila</i> tRNA repertoire evolution

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-24

  preprintOpen accessSenior author

  Eukaryotic genomes encode hundreds of transfer RNA genes ostensibly to ensure efficient translation. How these seemingly redundant tRNA copies arise and are naturally selected in metazoan genomes and populations remains largely unexplored, owing to challenges in accurate sequencing of tRNA loci and their transcripts. We leveraged long-read genome assemblies of 24 Drosophilid species to infer the origination times of the entire Drosophila melanogaster tRNA gene repertoire and found that continuous gain and loss of tRNA duplicates throughout 60 million years of divergence has resulted in rapid taxonomic restriction of isodecoding and isoaccepting copies—even producing one isodecoder specific to D. melanogaster. Moreover, we identified patterns of global codon usage, especially in lineage-specific genes, incongruous with translational efficiency hypotheses. Through generation of tRNA sequencing in D. melanogaster we observed that recently duplicated, taxonomically restricted tRNA copies had sexually dimorphic patterns of expression, fragmentation, and nucleoside modification. Our work implicates the emergence of taxonomically restricted tRNA genes as sources of regulatory diversity and reveals that sexual and natural selection affect the evolutionary dynamics of the tRNA gene family in metazoan species.

  PublisherOA PDFDOI

• Sexual conflict drive in the rapid evolution of new gametogenesis genes

  Seminars in Cell and Developmental Biology · 2024-02-02 · 8 citations

  reviewSenior authorCorresponding
  PublisherDOI

• The Rapid Evolution of De Novo Proteins in Structure and Complex

  Genome Biology and Evolution · 2024-05-16 · 11 citations

  articleOpen accessSenior author

  Recent studies in the rice genome-wide have established that de novo genes, evolving from noncoding sequences, enhance protein diversity through a stepwise process. However, the pattern and rate of their evolution in protein structure over time remain unclear. Here, we addressed these issues within a surprisingly short evolutionary timescale (<1 million years for 97% of Oryza de novo genes) with comparative approaches to gene duplicates. We found that de novo genes evolve faster than gene duplicates in the intrinsically disordered regions (such as random coils), secondary structure elements (such as α helix and β strand), hydrophobicity, and molecular recognition features. In de novo proteins, specifically, we observed an 8% to 14% decay in random coils and intrinsically disordered region lengths and a 2.3% to 6.5% increase in structured elements, hydrophobicity, and molecular recognition features, per million years on average. These patterns of structural evolution align with changes in amino acid composition over time as well. We also revealed higher positive charges but smaller molecular weights for de novo proteins than duplicates. Tertiary structure predictions showed that most de novo proteins, though not typically well folded on their own, readily form low-energy and compact complexes with other proteins facilitated by extensive residue contacts and conformational flexibility, suggesting a faster-binding scenario in de novo proteins to promote interaction. These analyses illuminate a rapid evolution of protein structure in de novo genes in rice genomes, originating from noncoding sequences, highlighting their quick transformation into active, protein complex-forming components within a remarkably short evolutionary timeframe.

  PublisherOA PDFDOI

• The three-dimensional genome drives the evolution of asymmetric gene duplicates via enhancer capture-divergence

  Science Advances · 2024-12-18 · 6 citations

  articleOpen accessSenior authorCorresponding

  Previous evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment by distally duplicated genes is an efficient mechanism for modulating tissue-specific production of preexisting proteins. By leveraging genomic asymmetries, we performed a coexpression analysis on Drosophila melanogaster tissue data to show the generality of enhancer capture-divergence (ECD) as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene HP6 / Umbrea as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple Drosophila species, we show that HP6/Umbrea was inserted near a preexisting, long-distance three-dimensional genomic interaction. We then use this data to identify a newly found enhancer ( FLEE1 ), buried within the coding region of the highly conserved, essential gene MFS18 , that likely neofunctionalized HP6/Umbrea . Last, we demonstrate ancestral transcriptional coregulation of HP6/Umbrea ’s future insertion site, illustrating how enhancer capture provides a highly evolvable, one-step solution to Ohno’s dilemma.

  PublisherDOI

• Human Gene Age Dating Reveals an Early and Rapid Evolutionary Construction of the Adaptive Immune System

  Genome Biology and Evolution · 2023-05-01 · 1 citations

  articleOpen access

  T cells are a type of white blood cell that play a critical role in the immune response against foreign pathogens through a process called T Cell Adaptive Immunity (TCAI). However, the evolution of the genes and nucleotide sequences involved in TCAI is not well understood. To investigate this, we performed comparative studies of gene annotations and genome assemblies of 28 vertebrate species and identified sets of human genes that are involved in TCAI, carcinogenesis, and ageing. We found that these gene sets share interaction pathways which may have contributed to the evolution of longevity in the vertebrate lineage leading to humans. Our human gene age dating analyses revealed that there was rapid origination of genes with TCAI-related functions prior to the Cretaceous eutherian radiation and these new genes mainly encode negative regulators. We identified no new TCAI-related genes after the divergence of placental mammals, but we did detect an extensive number of amino acid substitutions under strong positive selection in recently evolved human immunity genes suggesting they are co-evolving with adaptive immunity. More specifically, we observed that antigen processing and presentation and checkpoint genes are significantly enriched among new genes evolving under positive selection. These observations reveal an evolutionary process of T Cell Adaptive Immunity that were associated with rapid gene duplication in the early stages of vertebrates and subsequent sequence changes in TCAI-related genes. These processes together suggest an early genetic construction of the vertebrate immune system and subsequent molecular adaptation to diverse antigens.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM065429

  NIH · $1.1M · 2007

• Reference-quality Drosophila genome assemblies for evolutionary analysis of previously inaccessible genomic regions

  NIH · $1.7M · 2016–2022

• The Role of Gene Duplication in Resolving Sexually Antagonistic Selection in Drosophila

  NSF · $900k · 2020–2023

• Genomic analysis of feeding behavior and fitness in Drosophila

  NIH · $405k · 2012–2016

• DISSERTATION RESEARCH: Investigating the Functions and Phenotypes of Recently Originated Genes and Their Roles in Lineage-Specific Evolution

  NSF · $11k · 2011–2011

Frequent coauthors

• R. Mitchell Bush

  452 shared

• John M. Archibald

  Dalhousie University

  452 shared

• Kenneth H. Wolfe

  University College Dublin

  452 shared

• Jody Hey

  452 shared

• Richard C Lewontin

  389 shared

• Masatoshi Nei

  Temple University

  388 shared

• Walter M. Fitch

  388 shared

• Howard Ochman

  The University of Texas at Austin

  388 shared

Labs

• The Manyuan Long LaboratoryPI

Education

• B.A., Crop Plants and Genetics

  Sichuan Agricultural University

  1985

• M.S., Crop Plants and Genetics

  Sichuan Agricultural University

• Ph.D., Genetics and Evolution

  University of California at Davis

  1992

• Other, Genetics and Evolution

  Harvard University

  1997

Awards & honors

• John Simon Guggenheim Memorial Fellowship in Natural Science…
• AAAS Fellow (2014)
• Inaugural Edna K Papazian Distinguished Service Professor (2…
• CAREER Award, National Science Foundation (2003)
• David & Lucile Packard Fellow for Science & Engineering (199…