Research

 

Our main goal is to understand the influence that natural selection has played in the evolution of humans and other primates. We are intrigued by how adaptation has shaped the evolution of relevant phenotypes. How has natural selection influenced the acquisition of species-specific traits? What selective forces are responsible for phenotypic diversity within populations? How does past selection affect present-day phenotypes?

 

At present, we are actively working on (in no particular order):

Local adaptation

Through series of migration events, humans have colonizing virtually every habitable corner of the globe. Settling in such different environments was possible thanks to both cultural and biological adaptations. Although genetic differences among human groups are few and largely neutral, a few genetic differences are responsible for important phenotypic traits, including medically-related phenotypes. We are interested in measuring to what extent local selective pressures have influenced the genetic make up of humans, and which mechanisms mediated adaptation to each environment. We are particularly interested in complex genetic processes underlying local adaptation, such as changes in the strength or type of natural selection, and polygenic adaptation.

Currently, in humans our work focuses on human genetic adaptation to ambient temperature and diet, and on the use of ancient DNA to improve inferences on genetic local adaptation. We are working quite a lot on local adaptations in chimpanzees (see below).

Previous papers:

  • Human local adaptation of the TRPM8 cold receptor along a latitudinal cline.
    Key, FM, Abdul-Aziz, MA, Mundry, R, Peter, BM, Sekar, A, D’Amato, M, Dennis, MY, Schmidt, JM,  Andrés, AM.
    PLoS Genetics,
    14: e1007298 (2018). Full text. PDF.
  • Human adaptation and population differentiation in the light of ancient genomes.
    Key FM, Fu Q, Romagné F, Lachmann M, Andrés AM.
    Nature Comm 7:10775 (2016) Full text. PDF.
  • Selection on a Variant Associated with Improved Viral Clearance Drives Local, Adaptive Pseudogenization of Interferon Lambda 4 (IFNL4).
    Key FM, Peter B, Dennis MY, Huerta-Sánchez E, Tang W, Prokunina-Olsson L, Nielsen R, Andrés AM.
    PLoS Genetics 10:e1004681 (2014). Full text. PDF.

And read our review:

  • The Genomics of Human Local Adaptation.
    Rees JS, Castellano S, Andrés AM.
    Trends Genet. 2020 Jun;36(6):415-428. Full text. PDF.

More in our Publications page.

 

Ancient DNA

Recent technological advances have enabled the production of high-quality genome sequences of several archaic Homo individuals. This provides an unprecedented opportunity to study extinct populations and the ancestors of present-day modern humans. We use these genomes to study ancestral and modern human populations, with particular emphasis on the effects of natural selection in their evolution.

Currently, our work focuses on using ancient DNA to improve inferences on genetic adaptation.

Previous papers:

  • Ancient gene flow from early modern humans into Eastern Neanderthals.
    Kuhlwilm M, Gronau I, Hubisz MJ, de Filippo C, Prado-Martinez J, Kircher M, Fu Q, Burbano HA, Lalueza-Fox C, de la Rasilla M, Rosas A, Rudan P, Brajkovic D, Kucan Ž, Gušic I, Marques-Bonet T, Andrés AM, Viola B, Pääbo S, Meyer M, Siepel A, Castellano S.
    Nature 530: 29–433 (2016) Full text. PDF.
  • Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors.
    Dannemann D, Andrés AM, Kelso J.
    The American Journal of Human Genetics 98:22–33 (2016)
  • Patterns of coding variation in the complete exomes of three Neandertals.
    Castellano S, Parra G, Sánchez-Quinto FA, Racimo F, Kuhlwilm M, Kircher M, Sawyer S, Fu Q, Heinze A, Nickel B, Dabney J, Siebauer M, White L, Burbano HA, Renaud G, Stenzel U, Lalueza-Fox C, de la Rasilla M, Rosas A, Rudan P, Brajković D, Kucan Ž, Gušic I, Shunkov MV, Derevianko AP, Viola B, Meyer M, Kelso J, Andrés AM, Pääbo S.
    PNAS 111:6666-71 (2014). Full text. PDF.

And see our perspective:

  • Inferring human evolutionary history.
    Rees J and Andrés AM.
    Science 2022 Feb 25;375(6583):817-818.

More in our Publications page.

 

Primate population genomics


Considerable knowledge has accumulated on the influence of natural selection in specific human populations. Still, little is known about the conservation of such selective pressures, both among human populations and across different species. Loci under similar selective pressures are likely affected by common environmental factors and are behind shared phenotypes; loci under species- or population-specific selection are likely affected by local selective forces and are responsible for differential traits. Through a number of genomic approaches we aim at helping establish the level of conservation of different types of natural selection, and at identifying loci that are responsible for species- and population-specific traits.

Currently, our work focuses on identifying local genetic adaptation in wild chimpanzees (both to forest habitats and to savannah habitats), on the the effects of demography and mating behaviour in bonobos and, in collaboration, on the effects of adaptation in gorillas.

Previous papers:

  • Ghost admixture in eastern gorillas.
    Pawar H, Cuadros S, de Manuel M, van der Valk T, Lobon I, Alvarez-Estape M, Haber M, Dolgova O, Han S, Ayub Q, Bautista R, Kelley JL, Cornejo OE, Lao O, Andrés AM, Guschanski K, Ssebide B, Cranfield M, Tyler-Smith K, Xue Y, Prado-Martinez J, Marques-Bonet T, Kuhlwilm M.
    Nature Ecology and Evolution 2023. 7: 1503–1514. Full text.
  • Population dynamics and genetic connectivity in recent chimpanzee history.
    Fontserre C, … , Andrés AM, Hughes D, Kühl H, Lizano E, Arandjelovic M, Marques-Bonet T.
    Cell Genomics
    2022 6:100133. Full text. PDF.
  • Natural selection in the great apes.
    Cagan A*, Theunert C*, Laayouni H*, Santpere G*, Pybus M, Casals F, Prüfer K, Navarro A, Marques-Bonet T, Bertranpetit J#, Andrés AM#.
    Molecular Biology and Evolution, 33:3268-3283 (2016) Full text. PDF.
  • Chimpanzee genomic diversity reveals ancient admixture with bonobos. 
    Manuel M*, Kuhlwilm M*, Frandsen P*, Sousa V, Desai T, Prado-Martinez J, Hernandez-Rodriguez J, Dupanloup I, Lao O, Hallast P, Schmidt JM, Heredia-Genestar JM, Benazzo A, Barbujani G, Peter B, Kuderna LFK, Casals F, Angedakin S, Arandjelovic M, Boesch C, Kühl H, Vigilant L, Langergraber K, Novembre J, Gut M, Gut I, Navarro A, Carlsen F, Andrés AM, Siegismund HR, Scally A, Excoffier L, Tyler-Smith C, Castellano S, Xue Y, Hvilsom C, Marques-Bonet T.
    Science 354:477-481 )2016). Full text. PDF.
  • Great ape genetic diversity and population history.
    Prado-Martinez J, Sudmant PH, Kidd JM, Li H, Kelley JL, Lorente-Galdos B, Veeramah KR, Woerner AE, O’Connor TD, Santpere G, Cagan A, Theunert C, …, Andrés AM, Wall JD, Bustamante CD, Hammer MF, Eichler EE, Marques-Bonet T.
    Nature 499:471-5 (2013). Full text. PDF. 

 

We are also interested in their adaptation to zoonotic pathogens such as SIV, the precursor of HIV. SIV is not only highly prevalent among African primates, but also highly zoonotic. Understanding host genetic adaptation to SIV helps understand how species adapt to zoonotic pathogens and better understand HIV.

  • Genetic adaptations to SIV across chimpanzee populations.
    Pawar H, Ostridge HJ, Schmidt JM, Andrés AM.
    PLoS Genet. 2022. 18(8): e1010337. Full text. PDF.
  • The impact of genetic adaptation on chimpanzee subspecies differentiation.Schmidt JM, de Manuel M, Marques-Bonet T, Castellano S, Andrés AM.
    PLoS Genet. 2019 Nov 25;15(11):e1008485. Full text. PDF.

More in our Publications page.

 

Balancing selection


Balancing selection maintains advantageous diversity in populations by a variety of mechanisms. In humans it is responsible, for example, for the extreme levels of genetic diversity of the MHC locus, and for the fascinating equilibrium that maintains sickle-cell anemia alleles in malaria-suffering populations due to heterozygotes advantage. In other species, balancing selection maintains diversity that is crucial for sex determination, self-incompatibility, defense against pathogens, or escape from predators. Our goal is to understand the influence of balancing selection in the genome (its prevalence, conservation among populations and species, its most common targets) and to unravel the biological factors behind its signatures (its specific targets, the functional consequences of selected variants, their contribution to phenotypic diversity in populations). For this, we combine genomic approaches with detailed population genetics, computational, and experimental studies, that allow us to go from the genome to the phenotype.

We are currently working on whether balancing selection has contributed to facial diversity in primates, and to sexually antagonistic genetic variation in fruit flies.

Previous papers:

  • Signatures of long-term balancing selection in human genomes.
    Bitarello, BD, de Filippo, C, Teixeira, JC, Schmidt, JM, Kleinert, P, Meyer, D,  Andrés, AM.
    Genome Biology and Evolution, 10: 939-955 (2018). Full text. PDF.
  • Recent selection changes in human genes under long-term balancing selection.
    de Filippo C, Key FM, Ghirotto S, Benazzo A, Meneu JR, Weihmann A; NISC Comparative Sequence Program, Parra G, Green ED, Andrés AM.
    Molecular Biology and Evolution 33: 1435-1447 (2016) Full text. PDF.
  • Long-term balancing selection in LAD1 maintains a missense trans-species polymorphism in humans, chimpanzees and bonobos.
    Teixeira JC*, de Filippo C*, Weihmann A, Meneu JR, Racimo F, Dannemann M, Nickel B, Fischer A, Halbwax M, Andre C, Atencia R, Meyer M, Parra G, Paabo S, Andrés AM.
    Molecular Biology and Evolution 32: 1186-1196 (2015) Full text. PDF.

We have written a couple of reviews on this topic:

  • Inferring balancing selection from genome-scale data.
    Bitarello B, Brandt DYC, Meyer D and Andrés AM.
    Genome Biology and Evolution, 2023. 15(3):evad032. Full text.
  • Advantageous diversity maintained by balancing selection in humans.
    Key FM, Teixeira JC, de Filippo C, Andrés AM.
    Curr Opin Genet Dev. 29:45-51 (2014). Full text. PDF.

More in our Publications page.