Pan-genome

In the fields of

The genetic repertoire of a bacterial species is much larger than the gene content of an individual strain. [7] Some species have open (or extensive) pangenomes, while others have closed pangenomes.^[2] For species with a closed pan-genome, very few genes are added per sequenced genome (after sequencing many strains), and the size of the full pangenome can be theoretically predicted. Species with an open pangenome have enough genes added per additional sequenced genome that predicting the size of the full pangenome is impossible.^[4] Population size and niche versatility have been suggested as the most influential factors in determining pan-genome size.^[2]

Pangenomes were originally constructed for species of

The term 'pangenome' was defined with its current meaning by Tettelin et al. in 2005;[2] it derives 'pan' from the Greek word παν, meaning 'whole' or 'everything', while the genome is a commonly used term to describe an organism's complete genetic material. Tettelin et al. applied the term specifically to bacteria, whose pangenome "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."^[2]

Parts of the pangenome

Core

Is the part of the pangenome that is shared by every genome in the tested set. Some authors have divided the core pangenome in hard core, those families of homologous genes that has at least one copy of the family shared by every genome (100% of genomes) and the soft core or extended core,^[15] those families distributed above a certain threshold (90%). In a study that involves the pangenomes of Bacillus cereus and Staphylococcus aureus, some of them isolated from the international space station, the thresholds used for segmenting the pangenomes were as follows: "Cloud," "Shell," and "Core" corresponding to gene families with presence in <10%, 10 to 95%, and >95% of the genomes, respectively.^[16]

The core genome size and proportion to the pangenome depends on several factors, but it is especially dependent on the phylogenetic similarity of the considered genomes. For example, the core of two identical genomes would also be the complete pangenome. The core of a genus will always be smaller than the core genome of a species. Genes that belong to the core genome are often related to

Is the part of the pangenome shared by the majority of the genomes in a pangenome.[18] There is not a universally accepted threshold to define the shell genome, some authors consider a gene family as part of the shell pangenome if it shared by more than 50% of the genomes in the pangenome.^[19] A family can be part of the shell by several evolutive dynamics, for example by gene loss in a lineage where it was previously part of the core genome, such is the case of enzymes in the tryptophan operon in Actinomyces,^[20] or by gene gain and fixation of a gene family that was previously part of the dispensable genome such is the case of trpF gene in several Corynebacterium species.^[21]

Cloud

The cloud genome consists of those gene families shared by a minimal subset of the genomes in the pangenome,^[22] it includes singletons or genes present in only one of the genomes. It is also known as the peripheral genome, or accessory genome. Gene families in this category are often related to ecological adaptation.^{[citation needed]}

Classification

The pan-genome can be somewhat arbitrarily classified as open or closed based on the alpha value of the Heap law: ${\displaystyle N=kn^{-\alpha }}$ ^[23][15]

• ${\displaystyle N}$ Number of gene families.
• ${\displaystyle n}$ Number of genomes.
• ${\displaystyle k}$ Constant of proportionality.
• ${\displaystyle \alpha }$ Exponent calculated in order to adjust the curve of number of gene families vs new genome.

if ${\displaystyle \alpha \leq 1}$ then the pangenome is considered open.
if ${\displaystyle \alpha >1}$ then the pangenome is considered closed.

Usually, the pangenome software can calculate the parameters of the Heap law that best describe the behavior of the data.

Open pangenome

An open pangenome occurs when in one taxonomic lineage keeps increasing the number of new gene families and this increment does not seem to be

The pangenome of a genomic lineage accounts for the intra lineage gene content variability. Pangenome evolves due to: gene duplication, gene gain and loss dynamics and interaction of the genome with mobile elements that are shaped by selection and drift.^[26] Some studies point that prokaryotes pangenomes are the result of adaptive, not neutral evolution that confer species the ability to migrate to new niches.^[27]

Supergenome

The supergenome can be thought of as the real pangenome size if all genomes from a species were sequenced.^[28] It is defined as all genes accessible for being gained by a certain species. It cannot be calculated directly but its size can be estimated by the pangenome size calculated from the available genome data. Estimating the size of the cloud genome can be troubling because of its dependence on the occurrence of rare genes and genomes. In 2011 genomic fluidity was proposed as a measure to categorize the gene-level similarity among groups of sequenced isolates. ^[29] In some lineages the supergenomes did appear infinite,^[30] as is the case of the Bacteria domain.^[31]

Metapangenome

'Metapangenome' has been defined as the outcome of the analysis of pangenomes in conjunction with the environment where the abundance and prevalence of gene clusters and genomes are recovered through shotgun metagenomes.^[32] The combination of metagenomes with pangenomes, also referred to as "metapangenomics", reveals the population-level results of habitat-specific filtering of the pangenomic gene pool.^[33]

Other authors consider that Metapangenomics expands the concept of pangenome by incorporating

In 2018, 87% of the available whole genome sequences were bacteria fueling researchers interest in calculating prokaryote pangenomes at different taxonomic levels.^[22] In 2015, the pangenome of 44 strains of Streptococcus pneumoniae bacteria shows few new genes discovered with each new genome sequenced (see figure). In fact, the predicted number of new genes dropped to zero when the number of genomes exceeds 50 (note, however, that this is not a pattern found in all species). This would mean that S. pneumoniae has a 'closed pangenome'.^[37] 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.^[36] Another example of prokaryote pan-genome is Prochlorococcus, the core genome set is much smaller than the pangenome, which is used by different ecotypes of Prochlorococcus.^[38] Open pan-genome has been observed in environmental isolates such as Alcaligenes sp.^[39] and Serratia sp.,^[40] showing a sympatric lifestyle. Nevertheless, open pangenome is not exclusive to free living microorganisms, 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.^[41]