Washington, Feb 9 (ANI): Researchers have found new evidence of why mice, people and other vertebrate animals carry thousands of varieties of genes to make immune-system proteins named MHCs - even if some of those genes make vertebrate animals vulnerable to infections and to autoimmune diseases.
Major histocompatibility complex (MHC) proteins are found on the surfaces of most cells in vertebrate animals.
They distinguish proteins like themselves from foreign proteins, and trigger an immune response against these foreign invaders.
MHCs recognize invading germs, reject or accept transplanted organs and play a role in helping vertebrates smell compatible mates.
"Results of this study explain why there are so many versions of the MHC genes, and why the ones that cause susceptibility to diseases are being maintained and not eliminated," said biologist Wayne Potts of the University of Utah.
"They are involved in a never-ending 'arms race' that causes them, at any point in time, to be good against some infections but bad against other infections and autoimmune diseases."
By allowing a disease virus to evolve rapidly in mice, Potts, Jason Kubinak and other University of Utah scientists produced new experimental evidence for the arms race between genes and germs- known technically as "antagonistic co-evolution."
Most genes in humans and other vertebrates have only one or two "alleles," varieties or variants of a single gene.
Although any given person carries no more than 12 varieties of the six human MHC genes, the human population has anywhere from hundreds to 2,300 varieties of each of the six human genes that produce MHC proteins.
Scientists have proposed three theories for why so many MHC gene variants exist in vertebrate animal populations (invertebrates don't have MHCs), and say all three likely are involved in maintaining the tremendous diversity of MHCs.
Theory one states that an organism with more MHC varieties has a better immune response than organisms with fewer varieties, so over time, organisms with more MHCs are more likely to survive. However, this theory cannot explain the full extent of MHC diversity.
According to the second theory, previous research indicates that people and other animals are attracted to the smell of potential mates with MHCs that are "foreign" rather than "self."
Parents with different MHC variants produce children with more MHCs and thus stronger immune systems.
Antagonistic co-evolution between an organism and its pathogens: "we have an organism and the microbes that infect it," Kubinak said.
"Microbes evolve to better exploit the organism, and the organism evolves better defenses to fight off the infection."
One theory to explain this great diversity in MHC genes is that those competing interests over time favor retaining more diversity.
"You naturally keep genes that fight disease," said Kubinak.
"They help you survive, so those MHC genes become more common in the population over time because the people who carry them live to have offspring," Kubinak added.
Theory three states that pathogens - disease-causing viruses, bacteria or parasites - infect animals, which defend themselves with MHCs that recognize the invader and trigger an immune response to destroy the invading pathogen.
But over time, some pathogens mutate and evolve to become less recognizable by the MHCs and thus evade an immune response.
As a result, the pathogens thrive.
The researchers studied 60 mice that were genetically identical, except that the mice were divided into three groups, each with a different variety of MHC genes known as b, d and k, respectively.
A mouse leukemia virus named the Friend virus was grown in tissue culture and used to infect two mice from each of the three MHC types.
The fast-evolving virus grew in the mice for 12 days, attacking, enlarging and replicating within the spleen and liver. Virus particles in the spleen were collected, and the severity of illness was measured by weighing the enlarged spleen.
Then, virus taken from each of the first three pairs of mice (b, d and k) was used to infect another three pairs of mice with the same MHC types.
The process was repeated until 10 pairs of mice in each MHC type were infected, allowing the virus time to mutate.
In this first experiment, the biologists showed that they could get the Friend virus to adapt to and thus evade the MHC variants (b, d or k) in the mouse cells it attacked.
Next, the researchers showed that the virus adapted only to specific MHC proteins.
In the third experiment, the researchers showed that pathogen fitness (measured by the number of virus particles in the spleen) correlated with pathogen virulence (as measured by spleen enlargement and thus weight).
So the virus that evaded the MHC type b made mice with that MHC sicker.
The study has been published online in the journal Proceedings of the National Academy of Sciences (PNAS). (ANI)
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