What triggers genetic adaptation? Inquire with a finch.

Could an innovative method in genetic studies provide us with enhanced insight into how evolutionary alterations take place? That’s what recent findings regarding a familiar backyard avian species, the house finch, suggest. A pioneering pangenomic investigation has unveiled a significant DNA alteration that seems to have allowed the small bird immunity against specific diseases.

In the article “Fitness consequences of structural variation inferred from a House Finch pangenome,” featured in the Proceedings of the National Academy of Sciences (PNAS), Department of Organismic and Evolutionary Biology postdoctoral researcher Bohao Fang utilized state-of-the-art sequencing and a novel pangenomic technique to achieve a more comprehensive understanding of genetic adaptation. This method integrates the genomic data of numerous individual samples, examining a vast reservoir of genetic information and delivering “greater clarity on the genetic details,” according to Fang.

“Historically, researchers analyze the genetic diversity at a singular base pair [of DNA],” clarified Fang, an investigator in the Edwards lab. While prior investigations targeted specific genes attempting to unravel what Fang describes as “the inherited genetic mechanism governing disease resistance,” the limited scope of these studies yielded ambiguous conclusions. Conversely, by examining a more extensive segment of DNA, “We discover the long-read sequencing that permits us to identify critical large-scale structural changes that might otherwise remain unnoticed.”

In the house finch, this innovative technique uncovered a DNA inversion that has persisted for millions of years — which may have aided the bird in combating infection.

“The house finch serves as an excellent model for studying the coevolution between a host and a pathogen,” remarked Fang. He noted that this project was initiated in the aftermath of the COVID-19 crisis, as he developed an interest in the evolution of natural immunity to prevalent diseases. The house finch and its response to a bacterial pathogen causing conjunctivitis that spread across the U.S. since 1994 served as a notable case. The Museum of Comparative Zoology has preserved DNA samples of house finches sequenced as early as 2000, providing Fang “an invaluable resource” for his study.

This extensive collection permitted Fang to “observe the bigger picture in the DNA and understand how this wild avian species evolved in response to this disease.” By analyzing genetic samples collected over the years — both prior to and following an epizootic — “One can see how it adapted to develop some immunity to this ailment.”

“This provides us a clearer perspective regarding how in the wild, without vaccinations, evolution can react to emerging diseases.”

Though additional investigations remain necessary, Fang indicated that this research illustrates how a structural variant — defined as a large-scale DNA alteration — “could potentially play a role in adaptive evolution to combat the disease.”

“These present a remarkable real-world example of how a species copes with a new pathogen,” Fang elaborated. “This also offers insights into how other organisms, including humans, may respond genetically to infectious diseases over time.”

“Bohao’s research truly paves the way for the future of population genomic studies in avian species, and in natural populations at large. The pangenome methodologies he employed offer enhanced — and more equitable — representation of genetic variability within a species,” stated Scott V. Edwards, a professor of organismal and evolutionary biology, curator of ornithology, Alexander Agassiz Professor of Zoology in the MCZ, and co-author of the study.

“By not relying solely on a single reference individual to assess the variation of the entire population, the pangenome approach is not only significantly less biased but will additionally facilitate scientists studying wild species in making novel discoveries. The substantial inversion that Bohao identified was correlated with pathogen prevalence in house finches that would have remained hidden to us without these novel methodologies.”