Deleterious genes for a number of life-threatening diseases which palpably affect human fitness appear to persist in the gene pool at perplexingly high frequencies when you would think they would be eradicated over time by purifying natural selection. Now a group of scientists headed by Tobias Lenz of Harvard Med School and the Max Planck Institute for Evolutionary Biology have come up with the likely answer and it involves an evolutionary trade-off with the process that gives our immune systems the variability they need to counteract the many infectious diseases our environments throw at us. There is an easy-to-read precise of the work by Joseph Caspermeyer, in MBE.
In one part of their study Lenz and his colleagues examined over 160 genes in the MHC – the major histocompatibility complex – which is the area of the human genome that accounts for the cell surface molecules on our adaptive immune cells that recognise the antigens present on germs and guide those cells to attack them. Genes in this area, so-called HLA genes, have high genetic variability. As Lenz puts it, these classical HLA genes are scattered across the MHC region and exhibit exceptional allelic polymorphism and an extreme level of heterozygosity, which is thought to increase pathogen resistance and thus to be maintained by pathogen-mediated balancing selection. In other words it gives our immune systems the flexibility they need to counteract the multiple and constantly evolving threats from infectious microorganisms.
However, the downside to all this is that the MHC is enriched with a number of non-HLA genes that are known to be associated with diseases like autoimmune disease, cancer and schizophrenia. These can also persist at high frequency because they lie at such close proximity to the maintained HLA variants they too are maintained by genetic linkage. Lenz noted that non-HLA genes in very close proximity had a frequency more than two orders of magnitude that of non-HLA genes a little further away. Thus, even if some of these genes have a negative effect on human fitness we cannot get rid of them – they endure because they hang on to the coat-tails of genes that are essential, and have been essential through thousands of years, for human survival.