Three papers in this week's
Recessive loss-of-function mutations in the genes
Previous phylogenetic analyses of
Lahn and his coworkers sequenced
"None of those produced an outcome as dramatic as that observed," Lahn said. In each case, they found it extremely unlikely statistically that one haplotype would become so prevalent just by chance.
The researchers also found that many people have
All the evidence, Lahn said, points to an evolutionary history in which what is now the most common
In a second paper, Lahn's group shows that the same approximate history is likely for
Based on the average number of mutations between the most common haplotype and all of its minor variants, they found that the new clade of
According to these results, "the human brain is actually still evolving," Lahn said, "significantly after the emergence of these so-called anatomically modern humans."
Aside from the association with microcephaly, however, the idea that the selection on these two genes was due to brain size adaptation "is all speculation," said Morris Goodman of Wayne State University, "although, if the ideas aren't thrown forward, people will not be stimulated to try to figure out why this thing was positively selected."
The Varki lab looked at sialic acids and their receptors, as recent work has revealed differences between chimpanzees and humans in these proteins. They found that the sialic-acid receptor Siglec-11 is found as both a gene and a pseudogene in humans, chimpanzees, bonobos, gorillas, and orangutans. However, part of the human gene has more than 99% sequence homology to the pseudogene, but another part shows only about 95% homology. "It didn't make any sense," Varki said. "You'd expect the whole thing to have about the same age."
The researchers determined that part of the human pseudogene must have attached itself to one end of the gene at some point since the split of humans and chimps. This converted part contains a 5' upstream region and an exon that can bind sialic acid. Varki's group also found strong expression of the converted human gene in microglia; the original gene in chimpanzees and orangutans showed only occasional microglial staining.
This paper is "one of only a handful of published papers that document differences in brain organization at a molecular or cellular level between humans and chimpanzees," Todd Preuss of Emory University told
Studies of this type may help scientists to figure out why some diseases, such as Alzheimer's and AIDS, afflict humans but not other primates, Preuss suggested. "We can use genomic information to guide our search for human-specific phenotypes," Preuss said. "To me, that's the underlying significance of all of these papers."