What Separates Humans from Orangutans?

[This post is part of a series, What Separates Humans from the Animals?]

Glucocerebrosidase (GBA) is an enzyme that helps break down a fatty molecule that is present in the cell membrane. Mutations that disrupt its function result in Gaucher's disease, which can have a variety of symptoms with varying severity. An estimated 10-20% of disease-causing mutations are due to the fact that the GBA gene has a duplicate but broken copy next to it. In such cases, recombination between the normal GBA gene and its neighboring pseudogene results in the loss of a fully functional gene, leading to disease.

Wafaei and Choy looked at the GBA genes of several primate species, and it should come as no surprise that chimpanzees and gorillas also have one functional GBA gene and a neighboring pseudogene. I've drawn the following figure to represent their findings. (Note: pseudogenes are sometimes indicated by the Greek letter psi.)

(Click image to enlarge.)

Interestingly, orangutans appear to have two functional copies of GBA, while squirrel monkeys (a New World monkey) have a single GBA gene. The pseudogene is not found in non-primates, including mice, rats, and chickens, either. This suggests that a gene duplication event occured sometime after the lineages leading to squirrel monkeys and orangutans (and other apes) diverged.

The pseudogenes shared by humans, chimpanzees, and gorillas are not exactly the same. Each has some unique mutations that are not shared by the others. However, they all have at least one mutation in common: all three have a 55 base pair deletion in the same place, which appears to be the primary cause for the gene being broken. This is shown in a portion of Figure 4, which is an alignment of part of the various GBA genes and pseudogenes.

(Click image to enlarge.)

The human GBA sequence is at the top and is used as a reference. In the comparison sequences, differences are indicated by the changed letter. If the sequence is the same, it is indicated with a period. Missing sequences are represented with dashes. I've boxed the dashes, which are only in the pseudogene sequences.

This is like three copies of text missing the same run of 55 letters, and suggests that the deletion occurred in a common ancestor rather than three times independently. Unlike us, it appears that Orangutans are unlikely to get Gaucher's disease.

Reference:

Wafaei JR, Choy FY. Glucocerebrosidase recombinant allele: molecular evolution of the glucocerebrosidase gene and pseudogene in primates. Blood Cells Mol Dis. 2005 Sep-Oct;35(2):277-85. (Subscription Required)

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