About

Mia Levine, PhD, is the Principal Investigator of the Levine Lab at the University of Pennsylvania. Her research focuses on the evolutionary and functional diversification of DNA satellite-binding proteins, as well as the causes and consequences of nuclear lamina evolution. The lab also investigates telomere regulation during pre-implantation embryo development and the diversification of telomere elongation mechanisms in Drosophila. Through these studies, Levine and her team explore conflict-driven compensatory evolution within multi-protein complexes and paternal effect lethal evolution, contributing to a deeper understanding of molecular evolution and cellular processes.

Research topics

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

Selected publications

• Convergence and conflict among telomere specialized transposons across 60 million years of Drosophilid evolution

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-12 · 5 citations

  preprintOpen access

  Abstract The Drosophila telomere is one of the best-studied examples of active transposable elements (TEs) benefitting, rather than harming, a host genome. All Drosophila species lack telomerase and instead have telomeres composed of head-to-tail arrays of specialized retrotransposons. These TEs ostensibly act as mutualists by elongating chromosome ends, but evidence from species closely related to Drosophila melanogaster suggests that telomeric transposons may also antagonize their host genome. Importantly, the limited number of Drosophila species characterized thus far has precluded our ability to delineate idiosyncratic from universal evolutionary forces and genetic mechanisms that shape the history of these TEs. Here, we have surveyed long-read genome assemblies of over 100 species of Drosophila , identifying a total of 396 telomeric TE families. Our findings show that these telomere-specialized elements evolve rapidly and also undergo striking convergent evolution: the complete loss of telomeric TEs has occurred repeatedly across the genus while individual telomeric TE lineages have repeatedly lost one of their two protein-coding genes. These elements have also repeatedly undergone horizontal transfer between distantly related Drosophila lineages and have repeatedly captured host gene fragments that promote their selfish suppression of host TE-silencing systems. Furthermore, telomere specialization itself appears to have evolved convergently, as some non-telomeric families have gained the ability to target their insertions to telomeres. These results provide unprecedented resolution into the evolution of these unusual TEs and highlight several novel mechanisms by which they evolve in conflict both with each other and their host genome despite the essential telomere function they provide.

  PublisherOA PDFDOI

• A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance

  Current Biology · 2025-09-23 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-29 · 2 citations

  preprintOpen access

  Telomere length is inherited directly as a DNA sequence and as a classic quantitative trait controlled by many genes across the genome. Here, we show that neither paradigm fully accounts for telomere length inheritance, which also depends on a parent-of-origin effect on telomere elongation in the early embryo. By reciprocally crossing mouse strains with different telomere lengths, we find that telomeres elongate in hybrid embryos only when maternal telomeres are short and paternal telomeres are long. In the reciprocal cross, telomeres shorten. These differences in embryonic telomere elongation, which emerge before zygotic genome activation, predict adult telomere length. Moreover, when telomeres do elongate, we find molecular signatures of a recombination-based mechanism of telomere elongation, called the Alternative Lengthening of Telomeres (ALT) pathway, previously suggested to elongate telomeres in the pre-implantation embryo. We propose that ALT is triggered by a combination of genetic asymmetry in telomere length and epigenetic asymmetry between maternal and paternal chromosomes in the zygote. Our findings offer new insight into the complex interaction of genetic and epigenetic determinants of telomere length inheritance.

  PublisherDOI

• Recurrent innovation of protein-protein interactions in the Drosophila piRNA pathway

  The EMBO Journal · 2025-04-24 · 8 citations

  articleOpen access

  Despite being essential for fertility, genome-defense-pathway genes often evolve rapidly. However, little is known about the molecular basis of this adaptation. Here, we characterized the evolution of a protein interaction network within the PIWI-interacting small RNA (piRNA) genome-defense pathway in Drosophila at unprecedented scale and evolutionary resolution. We uncovered the pervasive rapid evolution of a protein interaction network anchored at the heterochromatin protein 1 (HP1) paralog Rhino. Through cross-species high-throughput yeast-two-hybrid screening, we identified three distinct evolutionary protein interaction trajectories across ~40 million years of Drosophila evolution. While several protein interactions are fully conserved, indicating functional conservation despite rapid amino acid-sequence change, other interactions are preserved through coevolution and were detected only between proteins within or from closely related species. We also identified species-restricted protein interactions, revealing insight into the mechanistic diversity and ongoing molecular innovation in Drosophila piRNA production. In sum, our analyses reveal principles of interaction evolution in an adaptively evolving protein-protein interaction network, and support intermolecular interaction innovation as a central molecular mechanism of evolutionary adaptation in protein-coding genes.

  PublisherDOI

• Rapid evolution to preserve a conserved function

  Nature Reviews Molecular Cell Biology · 2025-04-11

  review1st authorCorresponding
  PublisherDOI

• Rapid compensatory evolution within a multiprotein complex preserves telomere integrity

  Science · 2025-11-27 · 2 citations

  articleOpen accessSenior authorCorresponding

  Intragenomic conflict with selfish genetic elements spurs adaptive changes in subunits of essential multiprotein complexes. Whether and how these adaptive changes disrupt interactions within such complexes and threaten their essential functions remains unexplored. To investigate this, we exploited a Drosophila melanogaster multiprotein complex that protects telomeres from lethal fusions despite one subunit, HOAP (HP1/ORC–associated protein), evolving adaptively to restrict selfish telomeric retrotransposons. Swapping HOAP’s adaptively evolving interaction partner, HipHop (HP1-HOAP–interacting protein), between closely related Drosophila species disrupted HOAP recruitment to the telomere, leading to lethal telomere fusions. Reverting six adaptively evolving sites on HipHop’s interaction surface with HOAP, or introducing its conspecific HOAP, restored protein recruitment, telomere protection, and viability. Our in vivo, evolution-guided manipulations illuminate how intermolecular compensatory evolution preserves essential functions in the face of antagonism by selfish elements.

  PublisherOA PDFDOI

• The Genomic Landscape, Causes, and Consequences of Extensive Phylogenomic Discordance in Murine Rodents

  Genome Biology and Evolution · 2025-02-01 · 3 citations

  articleOpen access

  A species tree is a central concept in evolutionary biology whereby a single branching phylogeny reflects relationships among species. However, the phylogenies of different genomic regions often differ from the species tree. Although tree discordance is widespread in phylogenomic studies, we still lack a clear understanding of how variation in phylogenetic patterns is shaped by genome biology or the extent to which discordance may compromise comparative studies. We characterized patterns of phylogenomic discordance across the murine rodents-a large and ecologically diverse group that gave rise to the laboratory mouse and rat model systems. Combining recently published linked-read genome assemblies for seven murine species with other available rodent genomes, we first used ultraconserved elements (UCEs) to infer a robust time-calibrated species tree. We then used whole genomes to examine finer-scale patterns of discordance across ∼12 million years of divergence. We found that proximate chromosomal regions tended to have more similar phylogenetic histories. There was no clear relationship between local tree similarity and recombination rates in house mice, but we did observe a correlation between recombination rates and average similarity to the species tree. We also detected a strong influence of linked selection whereby purifying selection at UCEs led to appreciably less discordance. Finally, we show that assuming a single species tree can result in substantial deviation from the results with gene trees when testing for positive selection under different models. Collectively, our results highlight the complex relationship between phylogenetic inference and genome biology and underscore how failure to account for this complexity can mislead comparative genomic studies.

  PublisherDOI

• The ever-diversifying landscape of intra-genomic conflict

  Seminars in Cell and Developmental Biology · 2025-03-27

  review1st authorCorresponding
  PublisherDOI

• Paternal effects on telomere integrity during the sperm-to-embryo transition

  Current Opinion in Genetics & Development · 2025-04-25

  reviewOpen accessSenior author

  Telomeres are essential nucleoprotein structures that preserve our terminal DNA sequence and protect chromosome ends from fusion. Our vast knowledge of telomeres comes almost entirely from studies of healthy and diseased somatic cells. However, building evidence suggests that the molecules and mechanisms required for telomere integrity in somatic cells are insufficient to preserve telomere integrity during the sperm-to-embryo transition. Here, we review this growing body of work on telomere 'paternal effects', wherein zygotic telomere integrity is determined not by the genotype of the zygote but instead by the genotype of the father. Direct inheritance of sperm-specific proteins establishes paternal telomere epigenetic identity, while direct inheritance of sperm telomere length contributes to telomere length inheritance. Together, these investigations of telomere integrity through the sperm-to-embryo transition reveal potent paternal effects on zygotic telomere functions, with implications for human infertility.

  PublisherDOI

• eLife Assessment: The genomic landscape of transposable elements in yeast hybrids is shaped by structural variation and genotype-specific modulation of transposition rate

  2024-02-02

  peer-reviewOpen access1st authorCorresponding

  Transposable elements (TEs) are major contributors to structural genomic variation by creating interspersed duplications of themselves. In return, structural variants (SVs) can affect the genomic distribution of TE copies and shape their load. One long-standing hypothesis states that hybridization could trigger TE mobilization and thus increase TE load in hybrids. We previously tested this hypothesis by performing a large-scale evolution experiment by mutation accumulation (MA) on multiple hybrid genotypes within and between wild populations of the yeasts Saccharomyces paradoxus and Saccharomyces cerevisiae. Using aggregate measures of TE load with short-read sequencing, we found no evidence for TE load increase in hybrid MA lines. Here, we resolve the genomes of the hybrid MA lines with long-read phasing and assembly to precisely characterize the role of SVs in shaping the TE landscape. Highly contiguous phased assemblies of 127 MA lines revealed that SV types like polyploidy, aneuploidy and loss of heterozygosity have large impacts on the TE load. We characterized 18 de novo TE insertions, indicating that transposition only has a minor role in shaping the TE landscape in MA lines. Because the scarcity of TE mobilization in MA lines provided insufficient resolution to confidently dissect transposition rate variation in hybrids, we adapted an in vivo assay to measure transposition rates in various S. paradoxus hybrid backgrounds. We found that transposition rates are not increased by hybridization, but are modulated by many genotype-specific factors including initial TE load, TE sequence variants and mitochondrial DNA inheritance. Our results show the multiple scales at which TE load is shaped in hybrid genomes, being highly impacted by SV dynamics and finely modulated by genotype-specific variation in transposition rates.

  PublisherDOI

Frequent coauthors

• Gilles Hittinger

  Assistance Publique – Hôpitaux de Paris

  120 shared

• Robert W. Downs

  Virginia Commonwealth University

  106 shared

• Tracy T. Batchelor

  Dana-Farber Brigham Cancer Center

  100 shared

• Patrick Y. Wen

  100 shared

• Manmeet S. Ahluwalia

  100 shared

• Cécile Goujard

  Centre de recherche en Epidémiologie et Santé des Populations

  100 shared

• Rakesh K. Jain

  100 shared

• Jeffrey J. Olson

  Emory University

  100 shared

Labs

• Levine LabPI