Ancient Genomics

A natural extension to any ancient _meta_genomics project is to further investigate the specific genomes of the plethora of species and strains you may have detected. In this section of the book, we will look at the specific techniques used to reconstruct ancient genomes using standard genomics reference-based methods, but as always in the context of the short and damaged DNA fragments that are typical of ancient DNA.

Genome Mapping

An important step in the reconstruction of full genomic sequences is mapping. Even relatively short genomes usually cannot be sequenced as a single consecutive piece. Instead, millions of short sequence reads are generated from genomic fragments. These reads can be several hundred nucleotides in length but are considerably shorter for ancient DNA (aDNA).

For many applications involving comparative genomics these ‘reads’ have to be aligned to one or multiple already-reconstructed reference genomes in order to identify differences between the sequenced genome and any given contextual dataset. Aligning millions of short reads to much longer genome sequences in a time-efficient and accurate manner is a bioinformatics challenge for which numerous algorithms and tools have been developed. Each of these programs comes with a variety of parameters that can significantly alter the results and default settings are often not optimal when working with aDNA. Furthermore, read mapping procedures are often part of complex computational genomics pipelines and are therefore not directly applied by many users.

In this chapter we will take a look at specific challenges during read mapping when dealing with aDNA. We will get an overview of common input and output formats and manually apply a read mapper to aDNA data studying the direct effects of variation in mapping parameters. We will conclude the session with an outlook on genotyping, which is an important follow-up analysis step, that in turn is very relevant for down-stream analyses such as phylogenetics.

Phylogenomics

Phylogenetic trees are central tools for studying the evolution of microorganisms, as they provide essential information about their relationships and timing of divergence between microbial strains.

In this chapter, we will introduce basic phylogenetic concepts and definitions, and provide guidance on how to interpret phylogenetic trees. We will then learn how to reconstruct phylogenetic trees from DNA sequences using various methods ranging from distance-based methods to probabilistic approaches, including maximum likelihood and Bayesian phylogenetics. In particular, we will learn how to use ancient genomic data to reconstruct time-calibrated trees with BEAST2.