Tuesday, April 17, 2007

Macaques are not human   posted by p-ter @ 4/17/2007 07:11:00 AM

One of the more interesting parts of the paper reporting the sequencing of the rhesus macaque (also noted by Carl Zimmer) is that a number of mutations that cause Mendelian disease in humans are actually ancestral. That is, people with the disease have mutated to a sequence that's the same as the macaque one. Perhaps most notable are mutations in genes important in amino acid synthesis; one might expect these pathways to be well conserved. As the authors write:
In humans, these mutations greatly perturb the normal serum amino acid levels. Direct examination of macaque blood revealed lower concentrations of cystine and cysteine than in the human and slightly higher concentrations of glycine than in the human, but no increase in phenylalanine or ammonia, which might have been a predicted result of these changes. Although the effect of the observed alleles might be greatly influenced by compensatory mutations or other environmental factors, it remains a possibility that the basic metabolic machinery of the macaque may exhibit functionally important differences with respect to our own.
1. This is a strong argument for studying rare Mendelian diseases in humans. People sometimes bitch, "Who cares? Disease X affects 5 people in the entire world, why bother?". The answer, of course, is that those people are the human equivalents of knockout mice (to be horribly cold about it)-- people carrying rare recessive mutations are an important source of information about how those genes work in humans (see also this example), especially if those same genes are involved in different pathways in model organisms like the macaque or the mouse.

2. The ancestral disease alleles are also of prime interest for more detailed studies of selection. Deleterious mutations, of course, always have a probability of becoming fixed in a population; it takes more to show selection. But it's interesting ot note that the authors find a number of the mutations lead to mental retardation in humans. Could some of these genes be involved in human brain expansion and cognitive capabilities?

Labels: , ,