Infectious Diseases Determined Current Gene Makeup
June 5, 2012

Infectious Diseases Determined Current Gene Makeup

Connie K. Ho for

The author J.J. Dewey once said, "Consciousness cannot live in the present for the present cannot exist without the future and the past." This idea of the past influencing the present was seen in a recent report published in the online Early Edition of the Proceedings of the National Academy of Sciences that proposed that the inactivation of two genes linked to the immune system could have given some ancestors of modern humans greater protection from specific pathogenic bacterial strains.

The study, led by University of California, San Diego (UCSD) researchers with the help of international colleagues, helps to explain the decrease in human evolution that appeared about 100,000 years ago. At that time, the human population had reduced to five to ten thousand individuals who were living in Africa. Eventually, “behaviorally modern” humans appeared in the population, increased in numbers, and replaced other evolutionary cousins who existed at the time. Possible reasons for the change in population include gene mutations, cultural developments, climate change, and infectious diseases.

"In a small, restricted population, a single mutation can have a big effect, a rare allele can get to high frequency," explained senior author Dr. Ajit Varki, a professor of medicine and cellular and molecular medicine as well as co-director of the Center for Academic Research and Training in Anthropogeny at UCSD, in a prepared statement. "We've found two genes that are non-functional in humans, but not in related primates, which could have been targets for bacterial pathogens particularly lethal to newborns and infants. Killing the very young can have a major impact upon reproductive fitness. Species survival can then depend upon either resisting the pathogen or on eliminating the target proteins it uses to gain the upper hand."

Along with researchers in Japan, Italy, and other parts of the U.S., Varki and his team studied how the inactivation of two sialic acid-recognizing signaling receptors (siglecs) could adjust immune responses. These siglecs are part of an extensive family of genes that are thought to have been active in human evolution. With the project, the researchers discovered that the gene for Siglec-13 wasn´t included in the modern human genome even though it was seen in chimpanzees, who are the closest evolutionary relatives. The other siglec gene, Siglec-17, was still evident in humans, but had been changed slightly to create a short, inactive protein that wasn´t useful to invasive pathogens. The scientists based their project off a past study done with Dr. Victor Nizet, a professor of pediatrics and pharmacy at UCSD, which demonstrated how some pathogens could use siglecs to change the host immune response to benefit the microbe.

"Genome sequencing can provide powerful insights into how organisms evolve, including humans," remarked co-author Dr. Eric D. Green, a director of the National Human Genome Research Institute at the National Institutes of Health, in the statement.

The group was able to “resurrect” these “molecular fossils” in the experiment and discovered that the proteins were identified by the current pathogenic strains of E. coli and Group B Streptococci. The scientists looked at the molecular signatures around the genes and theorized that the ancestors of modern humans had to deal with this “selective sweep” and only humans with certain gene mutations could survive. As such, the population today has a non-functional Siglec-17 gene and an absent Siglec-13 gene.

"The modern bugs can still bind and could potentially have altered immune reactions," noted Varki, who also serves as director of the UCSD Glycobiology Research and Training Center, in the statement. "Speciation (the process of evolving new species from existing ones) is driven by many things“¦ We think infectious agents are one of them."