Characterization of MHC class II variation in feral pigeons – copy number variation, polymorphism, and selection

Every animal with a backbone that has jaws carries a sophisticated internal security system designed to recognize invaders. At the heart of this system lies a specific set of genes known as the Major Histocompatibility Complex. Think of these genes as the blueprints for a set of identification badges worn on the surface of cells. These badges display small fragments of proteins, acting like a visual report card that tells the immune system whether a cell is a healthy part of the body or a foreign intruder carrying a virus or bacteria. If the immune system recognizes the badge as foreign, it launches an attack to clear the threat. Because the world of pathogens is constantly changing, these identification badges must be incredibly diverse. If every individual in a species had the exact same badges, a single new disease could wipe out the entire population. Instead, nature favors a wide variety of badge designs, ensuring that at least some individuals will always be able to recognize and fight off new threats.

While scientists have studied these genetic systems in detail for humans and farm animals like chickens, the domestic pigeon has remained a mystery in this regard. These birds are everywhere in our cities, yet their specific immune genetics have not been thoroughly mapped. A team of researchers set out to fill this gap by examining the immune genes of feral pigeons living in five major cities across Poland. They focused on a specific part of the immune system responsible for fighting extracellular pathogens, looking closely at how many copies of these genes each bird carries and how much variety exists within those copies. Their work reveals that these common city birds possess a more complex genetic architecture than previously assumed, with individuals carrying different numbers of immune gene copies and showing distinct patterns of evolution between two ancient gene families.

The researchers captured 200 pigeons from Gdańsk, Krakow, Łódź, Warsaw, and Wrocław, collecting small blood samples from each bird. They then used advanced DNA sequencing to look at two specific lineages of immune genes, known as DAB1 and DAB2. These are ancient versions of the same gene family that have been preserved across bird species for millions of years. The team did not just count how many different versions of these genes existed; they also tried to figure out how many copies of each gene were present in a single bird's DNA. This is a difficult task because standard DNA tests often struggle to tell if a bird has one copy of a gene or several, especially when those copies are very similar. By carefully analyzing the patterns of the genetic sequences, the researchers were able to reconstruct the likely genetic makeup of each bird.

They found that the pigeons carried a moderate amount of variety in their immune genes. Across the entire group, the team identified 19 different versions of the DAB1 gene and 24 different versions of the DAB2 gene. However, the most surprising discovery was not just the variety, but the number of copies. Most of the birds appeared to have a single copy of each gene lineage, which is the standard expectation. But a significant number of individuals carried extra copies. Some birds had three copies of the DAB1 gene, and others had up to three copies of the DAB2 gene. This means that within the same species, different birds possess different numbers of these critical immune genes. The researchers determined that these extra copies were not random errors but were part of specific genetic packages, or haplotypes, that some birds inherited. In fact, they found that some pigeons carried one genetic package with a single gene copy and another package with three gene copies, resulting in a total of four copies in that individual.

The study also uncovered that these two ancient gene lineages, DAB1 and DAB2, are evolving in different ways. While they are related, they have taken distinct paths. The DAB2 lineage showed a stronger signal of diversifying selection, which is the evolutionary pressure that keeps the immune system changing to recognize new pathogens. This suggests that DAB2 is under intense pressure to stay diverse and adaptable. In contrast, the DAB1 lineage showed a stronger signal of recombination, a process where genetic material is swapped between copies to create new combinations. This indicates that DAB1 relies more on shuffling existing genetic material to create variety, while DAB2 relies on accumulating new changes. Furthermore, the researchers found that the extra gene copies in the pigeons were not highly diverse; they tended to be very similar to the main copy, suggesting they were relatively recent additions to the genome that had not yet had time to develop their own unique identities.

These findings suggest that the variation in the number of immune gene copies is not a rare accident but might be a common feature in birds. The fact that this variation exists in feral pigeons, which have a long history of living alongside humans and adapting to urban environments, highlights the complexity of their immune systems. The researchers noted that the overall genetic diversity in these pigeons was relatively low, which aligns with what is known about their history of domestication and population bottlenecks. Despite this lower diversity, the presence of multiple gene copies in some individuals adds a layer of complexity that could help them survive in pathogen-rich city environments. The study concludes that the domestic pigeon is a valuable model for understanding how immune systems evolve, particularly in how gene duplication and variation contribute to the ability to fight disease. By revealing that these common birds carry different numbers of immune genes, the research opens the door for further investigation into how these genetic differences affect the health of both the birds and the humans they live near.