To me, phylogenetics is one of the coolest ways to use human sequence diversity. I’m not an expert, but roughly speaking, the method involves looking at sequences among ancestral populations and comparisons to sequences in groups that have migrated out over space and time. In these out groups, recombination and mutation have caused genetic sequences to diverge – in some cases new alleles have been naturally selected for, and in most cases, new alleles thrived or crashed due the size and mating structure of a population. The genome carries the historical record of this change – the ultimate history book !
I recently had my Y-chromosome analyzed by the Genographic Project and was intrigued to discover a southwest asian heritage. More recently, Kenneth Kidd and colleagues report a detailed analysis of sequences in the KIR receptor gene complex on chromosome 19q13 and variation in the human leukocyte antigen (HLA) class I gene complex on chromosome 6p23. It has long been known that these regions are hypervariable, which is a good thing since our immune system exploits this diversity to counter ever-changing pathogen invasions – but how do two parts of the immune system continue to work together (KIR receptors bind to HLA antigens) when the separate, unlinked genomic regions show hypervariability ? Worse yet, if the KIR-HLA interaction is too weak, we are susceptible to infection, but, if too strong, we are susceptible to autoimmune attack. Quite a tight-wire to walk, amidst a deluge of pathogen invasions ! Kidd and colleagues use the ALFRED database to reveal some clues to the historical record of this. Apparently, the co-evolution is selective, where activating receptor (19q13) -ligand (6p23) complexes were strongly negatively selected for but not inhibitory receptor-ligand pairs.