University of Pennsylvania geneticists,performed a genetic analysis of 15 ethnic groups across Africa

University of Pennsylvania geneticists, in collaboration with an international team of scientists, performed a genetic analysis of 15 ethnic groups across Africa, looking for gene variants that could explain differing local susceptibility to malaria.

The international team was led by Sarah Tishkoff, a Penn Integrates Knowledge professor with appointments in the genetics department in Penn's Perelman School of Medicine and the biology department of biology in the School of Arts and Sciences, and Wen-Ya Ko, a postdoctoral fellow in the genetics department at the medical school.

"When you try to identify the variants that are associated with disease susceptibility, it's important to do a very fine scale study. Different populations evolve independently, to a certain degree, so different populations can come up with unique mutations," Ko said.

The life cycle of malaria depends on infecting red blood cells by binding to their surfaces, which is why mutations, such as sickle cell anaemia, that change the overall shape of those cells are thought to have experienced positive selection.

"Both host and the parasite try to fight back with mutations; it's a co-evolution arms-race that leaves a signature of selection on the genes," Ko explained.

Across the 15 population sets, the researchers focused on polymorphisms in a pair of genes that code for proteins called glycophorin A and glycophorin B.

These proteins exist on the surface of red blood cells, and changes to their shape affect the ability of the parasite causing malaria to bind to them and to infect the cells.

They noted an excess of genetic variation being maintained in the region of glycophorin A that plays a critical role of entry of the malaria parasite into the blood cell.

But a process known as "gene conversion," in which similar genes can acquire mutations from one another during cell division, complicates tracking the exact history of the mutation's spread.

"The parasite's genome is very highly mutable, and its generation time is short, as compared to humans, so having more mutations more quickly is helpful in keeping up," Ko said.