Paleogenomics of bovine domestication to enrich sustainable selection strategies – PATH2BOS

High throughput genomic methods tailored to ancient samples to screen through a large number of archaeological samples corresponding to cattle bones originating from the Mediterranean basin and dating from 50,000 years ago to the Middle Age. Identification through low-pass sequencing of the best-preserved samples and high coverage sequencing of the best-preserved samples. Development and use of bioinformatic pipelines dedicated to damaged DNA to map, correct errors and call genetic variability. Combination of population genomics and evolutionary genomics approaches to monitor past population exchanges; identify selected genes and reconstruct the timeline of genomic evolution upon domestication.

Ongoing project which results will be made first available through scientific publications.

The fine characterization of the genomic regions under selective pressure and of the history of these selection events will allow the establishment of genomic maps of the selection exerted on the cattle genome. This will highlight the genomic regions impacted by the evolution of the domestication process throughout history. This information will complement the functional genomic studies underway, thus contributing to a better understanding of the cattle genome. This should provide a new perspective on ongoing selection schemes. Moreover, it should favor the preservation of the ancestral diversity, in particular of characters that played an important role on the viability in a domestic context, thus contributing to long-term viability of domestic cattle populations.

Scientific publications and assessment of the patentability of developed methods are underway, several of them pending project finalization.

The aim of the Path2Bos project is to reconstruct the evolutionary path of cattle from its domestication starting about 10,000 years ago in Anatolia, during its later spread into Europe and Africa and up to now, through a paleogenomic analysis of fossils, the direct witnesses of evolution. The goal is to identify genomic regions that were selected at the early stages of domestication, corresponding to basic phenotypes that should be preserved in ongoing genetic selection schemes. The project is based on a previous paleogenetic characterization of a large number (~ 700) of 9,000- to 1,000-year-old archaeological bones of ancient domesticated cattle and their wild ancestors, the aurochs. We have genotyped the mitochondrial genomes and sequenced the hypervariable regions of almost 200 of these ancient bones, allowing us to assign reliably their mitochondrial haplogroups and to follow the evolution of populations from their initial domestication in Anatolia during the Neolithic as well as their spread and evolution in Europe and North Africa until the Middle Ages. Using sequence capture, we obtained complete mitogenomes from 40 of these samples representing the various clades, reconstructed the evolution and timing of radiation of aurochs’ populations, and untangled the impacts on population diversity of both climate changes during the Pleistocene-Holocene transition and initial domestication. We have sequenced the genome of a 9,000-year-old aurochs from the domestication centre in Anatolia that will serve as a reference genome to follow the genomic changes and selective sweeps during the domestication process. We propose to sequence about 30 of these ancient genomes and to compare them with genomes and phenotypic records from modern domestic animals to reconstruct many aspects of the selection pressure exerted during different prehistoric and historic periods. We will also sequence several individuals from modern hardy breeds to generate reference genetic data from breeds that have escaped recent selection schemes or that were selected for alternative phenotypes. Our data will be used in combination with modern genomic data from the 1,000 Bull Genomes consortium in various complementary ways to identify and to date signatures of selection during the cattle domestication process. We will screen for selection events that are either recent or old, complete or ongoing, acting on new variants or on standing variation. Using powerful tools to detect selective sweeps in genomes, ancient genomic data will provide the ability to date the various selection events, to identify the population(s) of origins onto which selection was exerted and to explore the validity of the various demographic models used to detect selective sweeps from modern genomic data. We will also use extensive GWAS data, produced by one of us using modern cattle, to reconstruct the past evolution of complex multigenic traits. Path2Bos will (1) improve the power and accuracy of the identification of genomic regions under selection, (2) estimate the strength of selection and date the origin of the corresponding selective events, (3) identify variants that were selected in the past and that have been lost in modern selection schemes, thereby pinpointing the genetic bases of phenotypic traits that might be useful to preserve for the long-term sustainability of cattle husbandry. Thus, it will provide an original and very useful cattle genome annotation data source to complement the genomic characterization efforts of modern cattle breeds and enrich the current selection strategies. A strong point of Path2Bos is the complementarity of the expertise and resources, including preliminary data, of the consortium partners, in particular paleogenomics and a large collection of characterized archeological samples, involvement in the 1000 Bull Genomes consortium and GWAS, selective sweep method developments and analyses of genomes and a high-throughput sequencing facility.