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 genetic adaptation in humans
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).
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.
And some papers:
- Human local adaptation of the TRPM8 cold receptor along a latitudinal cline.
Key, FM et al.,. PLoS Genetics, 14: e1007298 (2018). Full text. PDF. - Human adaptation and population differentiation in the light of ancient genomes.
Key FM, et al., 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, et al.,. PLoS Genetics 10:e1004681 (2014). Full text. PDF.
More in our Publications page.
Genetic adaptation in other primates
Unlike humans, other apes live in relatively small geographic areas, with every single subspecies of every great apes species (except humans) being endangered. Nevertheless some of them inhabit relatively diverse habitats. For example, while most chimpanzees live in forests, some populations live in woodland-savannah habitats. Actually chimpanzees are the only great ape that lives in open savannah –expect for humans, who moved from an arboreal life in the forest to a terrestrial one in the savannah, before migrating further and colonising the world.
We combine high-coverage from captive individuals and low-coverage genomic information from wild ones (often from faecal samples) with environmental information to establish whether, and how, wild populations of these species are genetically adapted to their particular habitat. This is important to understand the evolution and adaptive structure of the species, and aid their conservation.
- Local Genetic Adaptation to Habitat in Wild Chimpanzees.
Ostridge H, et al.,. BioRxiv 2024, doi: 10.1101/2024.07.09.601734. Full text.
- Natural selection in the great apes.
Cagan A*, Theunert C*, Laayouni H*, Santpere G*, et al.,. Molecular Biology and Evolution, 33:3268-3283 (2016) Full text. PDF.
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.
See our perspective:
- Inferring human evolutionary history.
Rees J and Andrés AM. Science 2022 Feb 25;375(6583):817-818. Full text.
And some papers:
- Ancient gene flow from early modern humans into Eastern Neanderthals.
Kuhlwilm M, et al.,. 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). Full text. - Patterns of coding variation in the complete exomes of three Neandertals.
Castellano S, et al.,. PNAS 111:6666-71 (2014). Full text. PDF.
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.
- Deep Genetic Substructure within Bonobos.
Han S*, de Filippo C*, et al.,. Current Biology 2024, Full text. - Ghost admixture in eastern gorillas.
Pawar H, et al.,. Nature Ecology and Evolution 2023. 7:1503–1514. Full text. - Population dynamics and genetic connectivity in recent chimpanzee history.
Fontserre C, et al.,. Cell Genomics 2022 6:100133. Full text. PDF. - Chimpanzee genomic diversity reveals ancient admixture with bonobos.
Manuel M*, Kuhlwilm M*, Frandsen P*, .et al.,. Science 354:477-481 )2016). Full text. PDF. - Great ape genetic diversity and population history.
Prado-Martinez J, et al.,. Nature 499:471-5 (2013). Full text. PDF.
Host adaptation to zoonotic pathogens
We are very interested in host adaptation to new 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.
We have written a couple of reviews on this topic:
- Inferring balancing selection from genome-scale data.
Bitarello B, et al., Genome Biology and Evolution, 2023. 15(3):evad032. Full text. - Advantageous diversity maintained by balancing selection in humans.
Key FM, et al., Curr Opin Genet Dev. 29:45-51 (2014). Full text. PDF.
Some papers:
- Signatures of long-term balancing selection in human genomes.
Bitarello, BD, et al.,. 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, et al.,. 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*, et al.,. Molecular Biology and Evolution 32: 1186-1196 (2015) Full text. PDF.
More in our Publications page.