Skip to main content Skip to navigation
Population Genomics of microorganisms and their hosts in health and disease Current Research

Evolutionary genomics of human populations in the face of disease

Our lab is interested in the genetic/genomic bases of health and disease. Because of our interest in the evolution of malarial parasites and bacterial pathogens and commensals, we are also interested in identifying and better understanding the demographic and selection scenarios that explain the evolution of genetic factors associated to the differential disease resistance and susceptibility to pathogens in human populations.

This said, it is our first interest to contribute to our understanding of the demographic history of human populations. Our lab maintains a very active collaboration with groups generating and analyzing genetic diversity in human populations and better understanding the process of human expansion worldwide and focalized in specific regions. Our specific involvement focus on understanding the patterns of genetic variation along the genome to characterize how different ancestries are distributed along the genomes in admixed populations.


We are particularly interested in using these complex demographic models underlying human evolution to better understand the evolution of regions of the genome under selection by human pathogens.

In this vein, we are working with Kimberly McManus a recent graduate from the Bustamante lab (now at LinkedIn) in collaboration with Martin Sikora at the Natural History Museum of Denmark to revisit the evolutionary history of DARC, a gene extremely important for the invasion of red cells by human malaria parasite Plasmodium vivax. DARC mutation preventing the expression of the gene in erythrocytes is highly prevalent (almost fixed) in African populations, and this observation was used to suggest that P. vivax originated in Africa and was an important selective factor for human populations. Work performed by the DiRienzo group at University of Chicago characterize for the first time the TMRCA and some initial estimates of selection for this locus. Our work is extending these results, using deep sequencing data across a large genomic dataset and using a combination of genomic analyses and simulations to infer the most likely selection scenario that explains the evolution of this locus.

We are also analyzing the locus responsible for hemochromatosis (accumulation of iron in blood). Mutations for hemochromatosis in the HFE gene have an interesting pattern of differentiation in European populations and we are analyzing different potential selection scenarios to explain its evolution. The most interesting scenario derives from the observation that mice with hemochromatosis are more susceptible to infections by Yersinia enterica than wild type mice.  The secretion system used by Yersinia enterica is similar to that one used by another member of the genus, Yersinia pestis (the bacteria responsible for black plague) that requires iron (type III secretion system). This led us to propose the hypothesis that the pattern of differentiation of HFE mutation in Europeans could have been driven by the spread of black plague from South to North.

The examples described above show some of the questions we are interested in addressing and we hope that we can synthesize the information gained from the evolutionary history of these loci and the evolutionary history of pathogens to really understand the evolution of interactions that lead to the long term establishment and spread of infectious diseases.

Relevant publications

  • Cook TF, Yee M-C, Muzzio M, Adams A, Bell R, Cornejo OE, Kelley JL, Bailliet G, Bravi CM, Bustamante CD, Kenny EE. (2016) GBStools: A unified approach for reduced representation sequencing and genotyping. PLoS Genetics. 12(2): e1005631. doi:10.1371/journal.pgen.1005631
  • Raghavan M, Steinrücken M, Harris K, Schiffels S, Rasmussen S, DeGiorgio M, Albrechtsen A, Valdiosera C, Ávila-Arcos MC, Malaspinas AS, Eriksson A, Moltke I, Metspalu M, Homburger JR, Wall J, Cornejo OE, Moreno-Mayar JV, Korneliussen TS, Pierre T, Rasmussen M, Campos PF, Damgaard Pde B, Allentoft ME, Lindo J, Metspalu E, Rodríguez-Varela R, Mansilla J, Henrickson C, Seguin-Orlando A, Malmström H, Stafford T Jr, Shringarpure SS, Moreno-Estrada A, Karmin M, Tambets K, Bergström A, Xue Y, Warmuth V, Friend AD, Singarayer J, Valdes P, Balloux F, Leboreiro I, Vera JL, Rangel-Villalobos H, Pettener D, Luiselli D, Davis LG, Heyer E, Zollikofer CP, Ponce de León MS, Smith CI, Grimes V, Pike KA, Deal M, Fuller BT, Arriaza B, Standen V, Luz MF, Ricaut F, Guidon N, Osipova L, Voevoda MI, Posukh OL, Balanovsky O, Lavryashina M, Bogunov Y, Khusnutdinova E, Gubina M, Balanovska E, Fedorova S, Litvinov S, Malyarchuk B, Derenko M, Mosher MJ, Archer D, Cybulski J, Petzelt B, Mitchell J, Worl R, Norman PJ, Parham P, Kemp BM, Kivisild T, Tyler-Smith C, Sandhu MS, Crawford M, Villems R, Smith DG, Waters MR, Goebel T, Johnson JR, Malhi RS, Jakobsson M, Meltzer DJ, Manica A, Durbin R, Bustamante CD, Song YS, Nielsen R, Willerslev E. (2015) Genomic evidence for the Pleistocene and recent population history of Native Americans. Science. Vol. 349 no. 6250 DOI: 10.1126/science.aab3884
  • Raghavan M, DeGiorgio M, Albrechtsen A, Moltke I, Skoglund P, Korneliussen TS, Grønnow B, Appelt M, Gulløv HC, Friesen TM, Fitzhugh W, Malmström H, Rasmussen S, Olsen J, Melchior L, Fuller BT, Fahrni SM, Stafford T Jr, Grimes V, Renouf MA, Cybulski J, Lynnerup N, Lahr MM, Britton K, Knecht R, Arneborg J, Metspalu M, Cornejo OE, Malaspinas AS, Wang Y, Rasmussen M, Raghavan V, Hansen TV, Khusnutdinova E, Pierre T, Dneprovsky K, Andreasen C, Lange H, Hayes MG, Coltrain J, Spitsyn VA, Götherström A, Orlando L, Kivisild T, Villems R, Crawford MH, Nielsen FC, Dissing J, Heinemeier J, Meldgaard M, Bustamante C, O’Rourke DH, Jakobsson M, Gilbert MT, Nielsen R, Willerslev E. (2014) The genetic prehistory of the New World Arctic. Science. 345 (6200) DOI: 10.1126/science.1255832
  • Rasmussen M, Anzick SL, Waters MR, Skoglund P, DeGiorgio M, Stafford TW Jr, Rasmussen S, Moltke I, Albrechtsen A, Doyle SM, Poznik GD, Gudmundsdottir V, Yadav R, Malaspinas AS, White SS 5th, Allentoft ME, Cornejo OE, Tambets K, Eriksson A, Heintzman PD, Karmin M, Korneliussen TS, Meltzer DJ, Pierre TL, Stenderup J, Saag L, Warmuth VM, Lopes MC, Malhi RS, Brunak S, Sicheritz-Ponten T, Barnes I, Collins M, Orlando L, Balloux F, Manica A, Gupta R, Metspalu M, Bustamante CD, Jakobsson M, Nielsen R, Willerslev E. (2014) The genome of a Late Pleistocene human from a Clovis burial site in western Montana. Nature. 506 (7487): 225 – 229 doi:10.1038/nature13025
  • Dewey FE, Chen R, Cordero SP, Ormond KE, Caleshu C, Karczewski KJ, Whirl-Carrillo M, Wheeler MT, Dudley JT, Byrnes JK, Cornejo OE, Knowles JW, Woon M, Sangkuhl K, Gong L, Thorn CF, Hebert JM, Capriotti E, David SP, Pavlovic A, West A, Thakuria JV, Ball MP, Zaranek AW, Rehm HL, Church GM, West JS, Bustamante CD, Snyder M, Altman RB, Klein TE, Butte AJ, Ashley EA. (2011) Phased whole genome genetic risk in a family quartet using a major allele reference sequence. PLoS Genetics. 7(9): e1002280. doi:10.1371/journal.pgen.1002280
  • Leung SW, Apponi LH, Cornejo OE, Kitchen CM, Valentini SR, Pavlath GK, Dunham CM, Corbett AH. (2009) Splice Variants of the Human ZC3H14 Gene Generate Multiple Isoforms of a Zinc Finger Polyadenosine RNA Binding Protein. Gene. 439(1-2):71-78.