Research group: The Orlando Group
How much major palaeo-environmental changes have shaped the geographic structure and demographic profiles of mammalian populations has been a recurrent theme in our research. Using mainly ancient DNA (aDNA) data, phylogenetic and serial coalescent approaches, we have reconstructed the diversity dynamics of several Megafauna populations over the last 50.000 years.
This work led to the revision of speciation and extinction times of several emblematic extinct species, such as cave bears (Curr Biol 2001, Mol Biol Evol 2002), and woolly rhinos (Mol Phyl Evol 2003). It also revealed recent climatic changes as a key demographic driver for most Megafauna species (Nature 2011), possibly through major remodeling of plant communities (Nature 2014).
Our work has focused on human evolution as well, with special interest in our relationships with our closest relatives, the Neandertals (Curr Biol 2006, Nature 2007, Curr Biol 2007), and more recently, addressing major migration events, such as the founding events of the New World (Nature 2014, 2015), including the New World Arctic (Nature 2010, Science 2014) and also of Eurasia (Science 2014, Nature 2015).
Since we officially started the lab in 2010, we have focused on developing integrative approaches for studying aDNA molecules, promoting the field of palaeomics by the merger of biochemistry, molecular biology, genomics and computational biology.
In particular, we have pioneered the use of true Single Molecule Sequencing (tSMS, Helicos) in aDNA research and thereby discovered important chemical features of aDNA molecules in relation with their degradation trajectory post-mortem (Genome Res 2011, BMC Genomics 2012).
By advancing our understanding of DNA damage processes, we have been able to tune our molecular tools to improve our ability to extract and manipulate ancient DNA molecules.
Similarly, we have contributed to a full series of bioinformatic tools and studies, all tailored to improving the sensitivity, the quality and the accuracy of the analyses underlying next-generation sequence datasets (Bioinformatics 2011, 2013; Nature Protocol 2014).
Our methodological developments have particularly benefitted to the reconstruction of the evolutionary history of one iconic mammal: the horse. We have generated the oldest genome characterized so far, that of a metapodial that has been preserved in the Yukon permafrost for about 700,000 years (Nature 2013). We also have characterized the complete genomes of several Pleistocene horses together with the genomes of a variety of modern domestic breeds (PNAS 2014a). Additionally, we characterized the first de novo assembly of the donkey genome, and genome-wide genetic variation across the whole equine family (PNAS 2014b). Additionally, we characterized the first de novo assembly of the donkey genome, and genome-wide genetic variation across the whole equine family (PNAS 2014). Incidently, this work resulted in the characterization of the complete genome sequence from the extinct quagga zebra, which kick-started ancient DNA research in the mid-eighties.
This represents an unprecedented genome sequence dataset for equids. We are currently scanning those genomes in order to identify the genetic changes that were specifically selected during horse domestication. Those changes contributed to major changes in human history, as mounted riding revolutionized warfare and, together with chariotry, facilitated the transportation of goods, people, languages, ideas and religion.
'We have also devised methods to track epigenetic changes over evolutionary times, either directly targeting DNA methylation marks (Sci Rep 2015) or exploiting indirect proxies of DNA methylation and nucleosome positioning (Genome Research 2014). This
resulted in the characterization of the first genome-wide nucleosome and methylation maps from an ancient human individual, paving the way for investigating the role of epigenetic changes in evolution (Science 2014).
Our research has been funded from AXA, the French-Danish Co-operation program from the French Embassy, Marie-Curie initiatives (FP7 CIG, FP7 IEF, H2020 IF, FP7 ITN), the Danish National Research Foundation (DNRF), the Danish Council for Independent Research (FNU), the Danish Agency for Research and Innovation (DASTI), the Vellux Fonden Foundation, the International Research Group Program from the King Saud University, Saudi Arabia, and the European Research Council (ERC).
1) MacHugh DE, Larson G, Orlando L. Taming the Past: Ancient DNA and the Study of Animal Domestication. Annu Rev Anim Biosci. 2016 Oct 28. PMID: 27813680 2)
2) Renaud G, Hanghøj K, Willeslev E, Orlando L. gargammel: a sequence simulator for ancient DNA. Bioinformatics. 2016 Oct 29. pii: btw670. PMID: 27794556
3) Boessenkool S, Hanghøj K, Nistelberger HM, Der Sarkissian C, Gondek A, Orlando L, Barrett JH, Star B. Combining bleach and mild pre-digestion improves ancient DNA recovery from bones. Mol Ecol Resour. 2016 Oct 28. PMID: 27790833
4) Librado P, Fages A, Gaunitz C, Leonardi M, Wagner S, Khan N, Hanghøj K, Alquraishi SA, Alfarhan AH, Al-Rasheid KA, Der Sarkissian C, Schubert M, Orlando L. The Evolutionary Origin and Genetic Makeup of Domestic Horses. Genetics. 2016 204:423-434. PMID: 27729493
5) Hanghøj K, Seguin-Orlando A, Schubert M, Madsen T, Pedersen JS, Willerslev E, Orlando L. Fast, Accurate and Automatic Ancient Nucleosome and Methylation Maps with epiPALEOMIX. Mol Biol Evol. 2016 Sep 13. pii: msw184. PMID: 27624717
6) Cruz-Dávalos DI, Llamas B, Gaunitz C, Fages A, Gamba C, Soubrier J, Librado P, Seguin-Orlando A, Pruvost M, Alfarhan AH, Alquraishi SA, Al-Rasheid KA, Scheu A, Beneke N, Ludwig A, Cooper A, Willerslev E, Orlando L. Experimental conditions improving in-solution target enrichment for ancient DNA. Mol Ecol Resour. 2016 Aug 27. PMID: 27566552
7) Leonardi M, Librado P, Der Sarkissian C, Schubert M, Alfarhan AH, Alquraishi SA, Al-Rasheid KA, Gamba C, Willerslev E, Orlando L. Evolutionary Patterns and Processes: Lessons from Ancient DNA. Syst Biol. 2016 Jul 5. pii: syw059. PMID: 27382011
8) Louvel G, Der Sarkissian C, Hanghøj K, Orlando L. metaBIT, an integrative and automated metagenomic pipeline for analysing microbial profiles from high-throughput sequencing shotgun data. Mol Ecol Resour. 2016 16:1415-1427. PMID: 27238636
9) Orlando L. Back to the roots and routes of dromedary domestication. Proc Natl Acad Sci U S A. 2016 113:6588-90.
10) Schubert M, Lindgreen S, Orlando L. AdapterRemoval v2: rapid adapter trimming, identification, and read merging. BMC Res Notes. 2016 9:88.