Chapter 5 : Human Genome Diversity: a Host Genomic Perspective of Host-Pathogen Interactions and Infectious Diseases

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Studies of multifactorial diseases, such as infectious diseases, must consider the complex interplay between environmental (microbial and nonmicrobial) and human (genetic and nongenetic) factors determining immunity to infection. There is increasing evidence that host genetic factors determine differences in host susceptibility to infection and contribute to the pattern of clinical disease. The diversity of the human genome varies according to the genomic region and human population considered. Two major population processes have a strong impact on the shaping of genetic diversity: founder effects and bottlenecks. The evolutionary dynamics of host-pathogen interactions lead to constant natural selection for adaptation and counter-adaptation in the two competing species. In the context of host-pathogen interactions, the first evidence of selection acting on a human gene was obtained for the sickle cell anemia HbS allele and malaria resistance. Selection pressure on the human genes involved in immune-related processes or, more generally, in host-pathogen interactions, is not limited to these instances. In this context variation in human genes conferring resistance to infectious diseases in the past may today provide us with information essential for improvements in our understanding of host-pathogen interactions. The identification of human genes that have been acted upon by natural selection, indicating an essential role in human survival over time, is therefore a complementary strategy for identifying genes that may be involved in different susceptibilities of the human host to infectious diseases today.

Citation: Quintana-Murci L. 2008. Human Genome Diversity: a Host Genomic Perspective of Host-Pathogen Interactions and Infectious Diseases, p 39-49. In Baquero F, Nombela C, Cassell G, Gutiérrez-Fuentes J (ed), Evolutionary Biology of Bacterial and Fungal Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815639.ch5
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Figure 1.

Schematic population dispersals and time-scales of modern humans around the world based on molecular genetics approaches. Humans probably began to migrate from East Africa to other parts of Africa around 100,000 YBP (years before present). They then left Africa, probably following two routes, to colonize Asia, Oceania, Europe and, lastly, the Americas. The timing of these migrations remains speculative because of uncertainties associated with estimates based on genetic data (Migration routes and timing are based on Cavalli-Sforza and Feldman, 2003).

Citation: Quintana-Murci L. 2008. Human Genome Diversity: a Host Genomic Perspective of Host-Pathogen Interactions and Infectious Diseases, p 39-49. In Baquero F, Nombela C, Cassell G, Gutiérrez-Fuentes J (ed), Evolutionary Biology of Bacterial and Fungal Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555815639.ch5
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