A team from the University of Nevada, Reno has produced a list of animals inferred to be free from endogenous Neu5Gc and thus ideal candidates for human consumption, xenotransplantation research, and use as model organisms. Humans are unable to synthesize Neu5Gc, a sialic acid present on the cell surface proteins of most deuterostomes, due to the inactivation of the CMAH gene about two million years ago.
According to the paper from a research team led by David Álvarez Ponce and published last month in Genome Biology and Evolution, Neu5Gc is a xenoantigen for humans, and consumption of Neu5Gc-containing foods, such as red meats, may promote inflammation, arthritis, and cancer. In addition, xenotransplantation of organs producing Neu5Gc can result in inflammation and organ rejection.
The researchers looked at 322 animal genomes to determine whether or not they have active CMAH genes. Next, they placed the results in the evolutionary tree of the animals, to determine at what moments of their evolution said gene was deactivated. This allowed them to understand why certain species have an active HCMA gene, while other similar ones do not.
"In a first analysis we scanned all the available genomes. We only found the gene in a few bacteria, in a pair of algae, and in the deuterostomes, a group of animals that includes vertebrates and echinoderms, among others. The non-deuterostomes animals did not present the gene. Next, we focused on the 322 deuterostomy genomes that were available," Alvarez-Ponce said.
So far, very few fish species had been studied to know whether or not they had amounts of toxic sugar. "Our analyzes show that there are fish that have the CMAH gene and others that do not, but for the moment the Neu5Gc sugar has been measured in very few of them. In fish that do have this gene, sugar is found in very small proportions in their meat, but in high quantities in caviar. This may be because the gene is expressed specifically in eggs or oviducts," he added.
Like humans, birds also do not have CMAH genes; so consuming chicken, turkey or duck does not have the negative effects of consuming red meat. Another group of animals that does not have CMAH genes are reptiles, except for one species of lizard. "The presence of the gene in this lizard was unexpected, and invalidates the belief (until now accepted) that the gene had been lost in an ancestor of all reptiles and birds," the team explained.
"It is possible that the deactivation of the CMAH gene during human evolution has protected humans from certain pathogens. For example, there is a type of malaria that needs Neu5Gc sugar to cause infection. This type of malaria affects some primates, but not humans," said Álvarez-Ponce.
Image: A sugar called Neu5Gc, present in red meat, some fish and dairy products, is related to the appearance of spontaneous tumors in humans. Image courtesy of Luis Carlos Díaz.