Date of Award

Spring 2026

Abstract

Long non-coding RNAs (lncRNAs) are widespread components of vertebrate genomes, yet theevolutionary principles governing their genomic positioning, origin, and functional associations remain incompletely understood. Here, we performed a comparative genomic analysis across 96 vertebrate species to investigate the spatial relationship between lncRNAs and protein-coding genes, their evolutionary trajectories within gene families, and their functional and genomic contexts.

We show that lncRNAs are consistently positioned in close proximity to protein-codinggenes across vertebrates, with distance distributions significantly deviating from random genomic placement in all species examined. Despite this non-random organization, genome-wide lncRNA–mRNA distance distributions were highly conserved across species. Ancestral state reconstruction of mixed orthogroups revealed that in 99.5% of cases, protein-coding genes predated the emergence of associated lncRNAs, indicating that lncRNAs overwhelmingly arise from pre-existing coding loci.

Gene families containing both lncRNAs and mRNAs exhibited significantly greaterevolutionary divergence than coding-only families, suggesting that lncRNA-linked orthogroups experience more dynamic evolutionary histories. Functional enrichment analyses further demonstrated that mixed orthogroups are strongly and specifically enriched for immune-related biological processes, a pattern not observed in divergence-matched coding-only controls. Finally, transposable element (TE) analyses revealed that TE density at mixed and mRNA-only loci correlates with genome-wide TE abundance, whereas lncRNA-only loci do not, supporting a model in which lncRNAs preferentially emerge within coding-associated genomic environments shaped by TE activity.

Together, these findings demonstrate that lncRNAs are evolutionarily and spatiallycoupled to protein-coding genes, frequently originate from established coding loci, and are disproportionately associated with rapidly evolving immune pathways. This study provides a broad evolutionary framework linking lncRNA emergence, gene family divergence, and immune system innovation across vertebrates.

Document Type

Master's Thesis

First Advisor

Matthew MacManes

Second Advisor

David Plachetzki

Third Advisor

Anna O'Brien

Degree Name

Master of Science

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