Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Human Evolutionary Genetics Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
The “Human Evolutionary Genetics” Unit focuses on the different factors (selective, demographic, and genomic) shaping the variability of the human genome. Their research activities are concentrated on the study of the genetic and functional diversity of genes involved in immune response or host-pathogen interactions. Using an evolutionary approach, their aims are (i) to explore the extent to which infectious agents have exerted selective pressures on human genes, (ii) to identify the genes having played a major biological role in host survival, and (iii) to delineate the redundant and non-redundant role of immunity-related genes in the natural setting. Their ultimate goal is to define the natural variability of host responses to infection in the human model and to understand the extent to which this phenotypic variation is under genetic and epigenetic control. To do so, their laboratory combines different approaches including population genetics, cellular genomics (transcriptomics and proteomics), immunology as well as computational modelling and development of new statistical frameworks.
Contribution to the programme
The contribution of the Quintana-Murci laboratory to the present programme will be the understanding of how the genetic and epigenetic diversity of the human host can contribute to the different susceptibility to, or severity of, infectious diseases. To this effect, they will combine different approaches, which include human population genetics, computational modelling and cellular genomics, to unravel (i) how natural selection has affected the genetic architecture of host defence genes (i.e. distinguishing Mendelian vs. complex disease genes), (ii) how host genetic diversity controls the variability of gene expression after infection (i.e., eQTLs) using ex vivo approaches, and (iii) how variable is the microRNA repertoire after infection and how this variability is genetically controlled by the host. The integration of these genomewide data into a clinical and epidemiological framework will provide new insights into host genes and pathways of major biological relevance for host survival against infection.
References over the past 5 years
1. Manry J, Laval G, Patin E, Fornarino S, Itan Y, Fumagalli M, Sironi M, Tichit M, Bouchier C, Casanova JL, Barreiro LB, Quintana-Murci L. Evolutionary genetic dissection of human interferons. J Exp Med. 2011, 208(13):2747-59.
2. Vasseur E, Patin E, Laval G, Pajon S, Fornarino S, Crouau-Roy B, Quintana-Murci L. The selective footprints of viral pressures at the human RIG-I-like receptor family. Hum Mol Genet. 2011, 20(22):4462-74.
3. Barreiro LB, Quintana-Murci L. From evolutionary genetics to human immunology: how selection shapes host defence genes. Nat Rev Genet. 2010, 11(1):17-30.
4. Barreiro LB, Ben-Ali M, Quach H, Laval G, Patin E, Pickrell JK, Bouchier C, Tichit M, Neyrolles O, Gicquel B, Kidd JR, Kidd KK, Alcaïs A, Ragimbeau J, Pellegrini S, Abel L, Casanova JL, Quintana-Murci L. Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet. 2009, 5(7):e1000562.
5. Quach H, Barreiro LB, Laval G, Zidane N, Patin E, Kidd KK, Kidd JR, Bouchier C, Veuille M, Antoniewski C, Quintana-Murci L. Signatures of purifying and local positive selection in human miRNAs. Am J Hum Genet. 2009, 84(3):316-27.
6. Louicharoen C, Patin E, Paul R, Nuchprayoon I, Witoonpanich B, Peerapittayamongkol C, Casademont I, Sura T, Laird NM, Singhasivanon P, Quintana-Murci L, Sakuntabhai A. Positively selected G6PD-Mahidol mutation reduces Plasmodium vivax density in Southeast Asians. Science. 2009, 326(5959):1546-9.
7. Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L. Natural selection has driven population differentiation in modern humans. Nat Genet. 2008, 40(3):340-5.