In the fields of molecular biology and genetics, a pan-genome is the entire set of genes for all strains within a clade. The pan-genome includes: the coregenome containing genes present in all strains within the clade, the accessory genome containing 'dispensable' genes present in a subset of the strains, and strain-specific genes. The study of the pan-genome is called pangenomics. Some species have open pan-genomes, while others have closed pan-genomes. For species with a closed pan-genome, very few genes are added per sequenced genome, and the size of the full pan-genome can be theoretically predicted. Species with an open pan-genome have enough genes added per additional sequenced genome that predicting the size of the full pan-genome is impossible. Population size and niche versatility have been suggested as the most influential factors in determining pan-genome size. The pan-genome can be broken down into a "core pan-genome" that contains genes present in all individuals, a "shell pan-genome" that contains genes present in two or more strains, and a "cloud pan-genome" that contains genes only found in a single strain. Pan-genomes were originally constructed for species of bacteria and archaea, but more recently eukaryotic pan-genomes have been developed, particularly for plant species. Plant studies have shown that pan-genome dynamics are linked to transposable elements. The significance of the pan-genome arises in an evolutionary context, especially with relevance to metagenomics, but is also used in a broader genomics context. An open access book reviewing the pan-genome concept and its implications, edited by Tettelin and Medini, was published in the spring of 2020.
History
Etymology
The term ‘pan-genome’ was defined with its current meaning by Tettelin et al. in 2005; it derives 'pan' from the Greek word παν, meaning 'whole' or 'everything', while genome is a commonly used term to describe an organism's complete genetic material. Tettelin et al. applied the term specifically to bacteria, whose pan-genome "includes a core genome containing genes present in all strains and a dispensable genome composed of genes absent from one or more strains and genes that are unique to each strain."
Original concept
The original pan-genome concept was developed by Tettelin et al. when they analyzed the genomes of eight isolates of Streptococcus agalactiae which could be described as a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Extrapolation suggested that the gene reservoir in the S. agalactiae pan-genome is vast and that new unique genes would continue to be identified even after sequencing hundreds of genomes.
Data structures
Pangenome graphs are emerging data structures designed to represent pangenomes and to efficiently map reads to them. They have been reviewed by Eizenga et al
Examples
A similar pattern was found in Streptococcus pneumoniae when 44 strains were sequenced. With each new genome sequenced fewer new genes were discovered. In fact, the predicted number of new genes dropped to zero when the number of genomes exceeds 50. This would mean that S. pneumoniae has a 'closed pan-genome'. The main source of new genes in S. pneumoniae was Streptococcus mitis from which genes were transferred horizontally. The pan-genome size of S. pneumoniae increased logarithmically with the number of strains and linearly with the number of polymorphic sites of the sampled genomes, suggesting that acquired genes accumulate proportionately to the age of clones. Another example for the latter can be seen in a comparison of the sizes of the core and the pan-genome of Prochlorococcus. The core genome set is logically much smaller than the pan-genome, which is used by different ecotypes of Prochlorococcus. A 2015 study on Prevotella bacteria isolated from humans, compared the gene repertoires of its species derived from different body sites of human. It also reported an open pan- genome showing vast diversity of gene pool.. Open pan-genome has been observed in environmental isolates such as Alcaligenes sp. and Serratia sp., showing a sympatric lifestyle.
Software tools
As interest in pan-genomes increased, there have been a number of software tools developed to help analyze this kind of data. In 2015, a group reviewed the different kinds of analyses and tools a researcher may have available. There are seven kinds of analyses software developed to analyze pangenomes: cluster homologous genes; identify SNPs; plot pangenomic profiles; build phylogenetic relationships of orthologous genes/families of strains/isolates; function-based searching; annotation and/or curation; and visualizations. The two most cited software tools at the end of 2014 were Panseq and the pan-genomes analysis pipeline. Other options include BPGA – A Pan-Genome Analysis Pipeline for prokaryotic genomes,
, and . A review focused on plant pan-genomes was published in 2015. Among the first software packages designed for plant pan-genomes were and .
