Gene conversion facilitates rapid evolution of inversions across avian immunoglobulin loci
- 1Cornell University
Abstract
The genomic architecture of immunoglobulin (IG) loci in birds has received remarkably little attention, despite their relevance to infectious disease susceptibility. One of the few exceptions is the domestic chicken, which has been found to use a completely different mechanism to generate a diverse IG repertoire than most vertebrates; rather than relying on V(D)J recombination, chickens primarily use somatic gene conversion. Whether this is true of all birds has remained unknown and untestable at scale until now. And importantly, it is not known how this alternative mechanism for antibody generation shapes, and is shaped by, genome evolution in birds. Leveraging IG locus annotations from 122 bird species generated through the Vertebrate Genomes Project and 17 species from the California Conservation Genomics Project, we show that avian IGH loci display a striking, previously unreported architecture of recurrent inverted duplications that generate direct and inverted copies of the same repeat unit, found in no other vertebrate lineage. Inversion density varies considerably across species, and population-level analyses reveal that these inversions evolve rapidly. We propose a model in which these inversions are actively maintained because they continuously replenish a pool of highly similar pseudogenes that serve as donors for somatic gene conversion, substituting for the large functional V gene repertoires other vertebrates use to generate IG diversity. This model makes a direct prediction: IGH loci should harbor few functional genes and many pseudogenes, while IGL loci, which typically lack this inversion architecture, should show the opposite pattern. Our cross-species analysis confirms this. To test the model at the level of the expressed repertoire, we generated paired whole-genome and Iso-seq data from a single wild-caught Red-winged Blackbird. Consistent with our predictions, a single terminal IGLV gene is diversified through gene conversion from surrounding pseudogenes, while IGH carries a large donor pool at which we also detect gene conversion. Together, these findings reveal that the molecular evolution of IG in birds is governed by fundamentally different constraints and processes than in the rest of known vertebrates.
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BibTeX
@misc{voss2026gene,
title = {{Gene conversion facilitates rapid evolution of inversions across avian immunoglobulin loci}},
author = {K. Voss and D. Hardesty and A. Zamyatin and M. Pospelova and Y. Zhu and M. R. Carrasco and A. Bankevich and L. Campagna and Y. Safonova and M. Pennell},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.05.749481},
url = {https://www.biorxiv.org/content/10.64898/2026.09.05.749481v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Gene conversion facilitates rapid evolution of inversions across avian immunoglobulin loci
AU - K. Voss
AU - D. Hardesty
AU - A. Zamyatin
AU - M. Pospelova
AU - Y. Zhu
AU - M. R. Carrasco
AU - A. Bankevich
AU - L. Campagna
AU - Y. Safonova
AU - M. Pennell
PY - 2026
DA - 2026/09/05
PB - bioRxiv
DO - 10.64898/2026.09.05.749481
UR - https://www.biorxiv.org/content/10.64898/2026.09.05.749481v1
AB - The genomic architecture of immunoglobulin (IG) loci in birds has received remarkably little attention, despite their relevance to infectious disease susceptibility. One of the few exceptions is the domestic chicken, which has been found to use a completely different mechanism to generate a diverse IG repertoire than most vertebrates; rather than relying on V(D)J recombination, chickens primarily use somatic gene conversion. Whether this is true of all birds has remained unknown and untestable at scale until now. And importantly, it is not known how this alternative mechanism for antibody generation shapes, and is shaped by, genome evolution in birds. Leveraging IG locus annotations from 122 bird species generated through the Vertebrate Genomes Project and 17 species from the California Conservation Genomics Project, we show that avian IGH loci display a striking, previously unreported architecture of recurrent inverted duplications that generate direct and inverted copies of the same repeat unit, found in no other vertebrate lineage. Inversion density varies considerably across species, and population-level analyses reveal that these inversions evolve rapidly. We propose a model in which these inversions are actively maintained because they continuously replenish a pool of highly similar pseudogenes that serve as donors for somatic gene conversion, substituting for the large functional V gene repertoires other vertebrates use to generate IG diversity. This model makes a direct prediction: IGH loci should harbor few functional genes and many pseudogenes, while IGL loci, which typically lack this inversion architecture, should show the opposite pattern. Our cross-species analysis confirms this. To test the model at the level of the expressed repertoire, we generated paired whole-genome and Iso-seq data from a single wild-caught Red-winged Blackbird. Consistent with our predictions, a single terminal IGLV gene is diversified through gene conversion from surrounding pseudogenes, while IGH carries a large donor pool at which we also detect gene conversion. Together, these findings reveal that the molecular evolution of IG in birds is governed by fundamentally different constraints and processes than in the rest of known vertebrates.
ER -