Massive gene presence/absence variation in the mussel genome as an adaptive strategy: first evidence of a pan-genome in Metazoa

Abstract

Mussels are ecologically and economically relevant edible marine bivalves, highly invasive and resilient to biotic and abiotic stressors causing recurrent massive mortalities in other species. Here we show that the Mediterranean mussel Mytilus galloprovincialis has a complex pan-genomic architecture, which includes a core set of 45,000 genes shared by all individuals plus a surprisingly high number of dispensable genes (~15,000). The latter are subject to presence/absence variation (PAV), i.e., they may be entirely missing in a given individual and, when present, they are frequently found as a single copy. The enrichment of dispensable genes in survival functions suggests an adaptive value for PAV, which might be the key to explain the extraordinary capabilities of adaptation and invasiveness of this species. Our study underpins a unique metazoan pan-genome architecture only previously described in prokaryotes and in a few nonmetazoan eukaryotes, but that might also characterize other marine invertebrates. Significance statementIn animals, intraspecific genomic diversity is generally thought to derive from relatively small-scale variants, such as single nucleotide polymorphisms, small indels, duplications, inversions and translocations. On the other hand, large-scale structural variations which involve the loss of genomic regions encoding proteincoding genes in some individuals (i.e. presence/absence variation, PAV) have been so far only described in bacteria and, occasionally, in plants and fungi. Here we report the first evidence of a pan-genome in the animal kingdom, revealing that 25% of the genes of the Mediterranean mussel are subject to PAV. We show that this unique feature might have an adaptive value, due to the involvement of dispensable genes in functions related with defense and survival.

Molecular Diversity of Mytilin-Like Defense Peptides in Mytilidae (Mollusca, Bivalvia)

“…A total of six different mytilin sequences were identified in M. californianus, representing the first report of this AMP family in the species. In general, these sequences showed a higher level of similarity with the mytilins from M. coruscus (in the range of 78-87%) than with those found in the M. edulis complex, consistently with the phylogenetic placement of the species [25]. The length of the precursor and mature was very similar (102-106 aa and 34-35 aa, respectively), and all sequences displayed a canonical cysteine array ( Figure 3).…”

“…mytilins were placed, intermixed, in a well supported monophyletic clade (96% posterior probability, see Figure 5), and overall displayed a lower level of molecular diversity compared with Perna. The sequences from the different Mytilus species were often mixed, consistently with their hypothesized recent origin by gene duplication, as well as with the proven dispensable nature of some M. galloprovincialis mytilin genes [25]. The Bayesian tree also indicated the derivation of pseudomytilins from canonical mytilins, as suggested by their placement in a divergent highly supported early-branching clade (100% posterior probability, see Figure 5).…”

“…All the three genera where mytilin sequences were identified belong to one of the two major evolutionary lineages identified by Morton and colleagues, i.e., clade A. Although Trichomya is currently considered as a member of the subfamily Septiferinae [30], recent molecular data support its close relatedness to Mytilus, suggesting that this genus should be placed within the subfamily Mytilinae [25,29]. In light of this observation, the presence of mytilins in Trichomya would be consistent with a shared ancestry with the Mytilus genus.…”

“…The application of next generation sequencing to the Mytilidae [23,24], in particular thanks to the feasibility of whole genome sequencing approaches [25][26][27], now offers new opportunities for the discovery of novel AMP sequences in species that have been so far subjected to limited scientific attention. In the present work we describe for the first time the presence of mytilin-like sequences in two new genera, i.e., Perna Philipsson 1788 and Trichomya Ihering 1900, which implies the possibility that related sequences might be found in other phylogenetically related species in the near future.…”

Single individual structural variant detection uncovers widespread hemizygosity in molluscs

“…In pigs, the size of the pig pan-genome, estimated based on the resequencing of 12 individuals, revealed the presence of 72.5 Mb additional genomic sequence [10]. High levels of genomic heterozygosity and gene presence/absence have been recorded in the bivalve molluscs Mytilus galloprovincialis [11] and Crassostrea gigas [12]. In M. galloprovincialis, a species characterized by an open pangenome (i.e.…”