Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host

Abstract

The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10-/- mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64Mb genome to 200-500X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host.

Passage of Campylobacter jejuni through the chicken reservoir or mice promotes phase variation in contingency genes Cj0045 and Cj0170 that strongly associates with colonization and disease in a mouse model

“…The work by Jerome et al (2011) supports the proposed model. These researchers demonstrated that passage of C. jejuni NCTC11168 through C57Bl6 IL10-deficient mice increased colonization and disease symptoms, and this process was accompanied by phase variation in specific contingency genes.…”

“…Illumina sequence analysis of these bacterial populations demonstrated that the genetic changes observed during animal passage occurred almost exclusively in contingency genes, strongly suggesting that phase variation in contingency genes during passage in chickens and/or mice in our study is directly responsible for enhanced colonization and disease. Jerome et al (2011) did not, however, directly link changes in any one contingency gene to increased colonization and disease.…”

“…The number and frequency of each allele in fragment analysis agreed with sequence analysis (Table S2). The genotype of 19 contingency genes in a non-passaged population of strain NCTC11168 as determined by fragment analysis was confirmed by Illumina sequence analysis of strain NCTC11168 grown under similar culture conditions (Jerome et al, 2011).…”

“…In contrast, C. jejuni strain NCTC11168, sequenced by Parkhill et al (2000), colonized both animals at high frequency and caused disease symptoms in the IL-10-deficient mouse model similar to those observed in human patients (Mansfield et al, 2007). This model has been utilized effectively in several subsequent studies (Mansfield et al, 2008;Bell et al, 2009;Wilson et al, 2010;Jerome et al, 2011).…”

The roles of standing genetic variation and evolutionary history in determining the evolvability of anti-predator strategies

“…While an allele may be mildly deleterious or confer no fitness advantage over other forms under one set of environmental conditions [6], that allele may become beneficial if the environment changes. As selection can act only on available variation, SGV provides a potential means for more rapid adaptive evolution ( [7][8][9][10][11][12][13][14][15][16][17][18][19][20]; reviewed in [21]) compared with the de novo mutations [5,22], particularly if the environment changes (e.g. if a new predator or competitor invades the system, or if abiotic conditions change).…”