PMC:1271393 / 62120-64698 JSONTXT

{"project":"2_test","denotations":[{"id":"16252244-14971025-2049700","span":{"begin":859,"end":863},"obj":"14971025"}],"text":"Conclusions\nThe need of continuous evolution for both the human host and the pathogens is predicted by the Red Queen hypothesis (Van Valen 1973; Bell 1982), in reference to the remark of the Red Queen to Alice in Through the Looking Glass (Carroll 1872): “Now, here, you see, it takes all the running you can do, to keep in the same place.” This metaphor provides a conceptual framework for understanding how interactions between the two species lead to constant natural selection for adaptation and counteradaptation. In this context, one feature exploited by the host immunity genes to increase their defense potential is gene duplication by retention, through conservation of one duplicate, of the currently useful function of the encoded protein, while its twin is liberated to mutate and possibly acquire novel functions (Ohno 1970; Trowsdale and Parham 2004). The lectins CD209 and CD209L represent a prototypic model of a duplicated progeny of ancestral genes that interact with a vast spectrum of pathogens. Our results clearly indicate that these duplicated genes have evolved, and might still evolve, under completely different evolutionary pressures. Whereas one, CD209, shows signals of strong conservation, its paralogue, CD209L, exhibits an excess of sequence diversity compatible with the action of balancing selection. In addition, the strong contrast observed in length variation of the neck region between the two genes may have important consequences in medical genetics. In this context, association studies are now needed that correlate length variation of the neck region and susceptibility to infectious diseases whose etiological agents are known to interact with one (or both) of these lectins.\nMore generally, our study has revealed that even a short segment of the human genome can help uncover an extraordinarily complex evolutionary history, including different pathogen pressures on host immunity genes, as well as traces of ancient population structure in the African continent. The coming years will certainly bring unprecedented large data sets of sequence diversity, genomewide and populationwide, with each genomic region possibly revealing a different aspect of human history. The integration of all these apparently independent pieces of the same reality will provide us with a much broader and more realistic view of the demographic history of the human species, as well as of human adaptation to the different environmental conditions imposed not only by pathogens but also by other major factors such as climate and nutritional resources."}