Atlantic herring travel in massive schools that can contain hundreds of millions — and sometimes even billions — of fish. While this abundance is characteristic for one of the most successful vertebrates on Earth, it also creates ideal conditions for viruses, bacteria and parasites to spread.
Now, an international team of researchers led by the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) has discovered that Atlantic herring have an extraordinary level of diversity in a group of immune genes that help recognize invading pathogens. Published in Science Advances, the study found that the fish's genetic diversity in these immune genes exceeds what has been reported in any other vertebrate studied so far, including humans.
The researchers believe this remarkable diversity reflects millions of years of natural selection as Atlantic herring continually adapted to defend themselves against an ever-changing array of pathogens.
"Our previous work has revealed many genes contributing to ecological adaptation in the Atlantic herring, but it has been very challenge to study immune genes because they often occur as clusters of closely related genes," said Dr. Leif Andersson , a professor in VMBS' Department of Veterinary Integrative Biosciences and principal investigator of the study.
Built to defend against disease
The genes at the center of the study belong to the major histocompatibility complex, or MHC, which plays a critical role in the vertebrate immune system.
MHC molecules help the body recognize harmful invaders by presenting fragments of viruses, bacteria, parasites and other foreign proteins to immune cells, allowing the immune system to mount a defense. Because different MHC variants recognize different pathogens to different degrees, greater genetic diversity generally provides broader protection against disease.
MHC genes are already known to be among the most diverse protein-coding genes in vertebrates. However, accurately measuring that diversity has long been a challenge because these regions of the genome are highly complex.
To better understand how these genes have evolved in Atlantic herring, the research team sequenced the complete genomes of 14 fish collected from three geographic locations across the species' range. Using long-read sequencing technology (a method that allows DNA to be read in one long, continuous stretch instead of in shorter fragments), they assembled high-quality genomes that allowed them to examine the complex MHC gene regions with unprecedented resolution.
"The use of long-read sequencing was the key to success because it allowed us to characterize clusters of closely related sequences with high accuracy, which was not possible with more widely use short-read sequencing," said Dr. Minal Jamsandekar , Andersson's former doctoral student and a co-author of the study.
Diversity unlike anything seen before
The researchers found that Atlantic herring possess exceptionally high diversity in their MHC class II genes, a group of immune genes involved in recognizing pathogens and activating immune responses.
The diversity stems from two key factors. First, the portions of the MHC molecules responsible for binding and presenting foreign proteins differ dramatically among individuals. Second, the number of MHC genes themselves varies considerably from fish to fish, meaning individual herring carry different combinations of immune genes.
Together, these differences create unique immune profiles for individual fish across the population, giving the species an exceptionally broad capacity to recognize and respond to pathogens.
The findings suggest this extraordinary diversity has been shaped by strong natural selection driven by the evolutionary "arms race" between Atlantic herring and the viruses, bacteria and parasites they encounter throughout their lives.
New insights into immune system evolution
Beyond helping explain how Atlantic herring have adapted to life under constant pathogen pressure, the findings provide new insight into the evolution of MHC genes and the forces that shape immune gene diversity across vertebrates.
The study also demonstrates the power of long-read genome sequencing to resolve some of the most complex regions of vertebrate genomes, opening new opportunities to study the evolution of immune genes in other vertebrate species.
"This is the first study of the highly variable MHC genes in natural populations where long-read sequencing has been used," Andersson said. "It is now important to apply this approach in other species to reveal if the extreme level of genetic diversity is restricted to highly abundant species like the herring or more widespread than previously thought."
By Camryn Haines, Texas A&M University College of Veterinary Medicine and Biomedical Sciences
