Natural selection on individual variation in tolerance of gastrointestinal nematode infection

Abstract

Hosts may mitigate the impact of parasites by two broad strategies: resistance, which limits parasite burden, and tolerance, which limits the fitness or health cost of increasing parasite burden. The degree and causes of variation in both resistance and tolerance are expected to influence host-parasite evolutionary and epidemiological dynamics and inform disease management, yet very little empirical work has addressed tolerance in wild vertebrates. Here, we applied random regression models to longitudinal data from an unmanaged population of Soay sheep to estimate individual tolerance, defined as the rate of decline in body weight with increasing burden of highly prevalent gastrointestinal nematode parasites. On average, individuals lost weight as parasite burden increased, but whereas some lost weight slowly as burden increased (exhibiting high tolerance), other individuals lost weight significantly more rapidly (exhibiting low tolerance). We then investigated associations between tolerance and fitness using selection gradients that accounted for selection on correlated traits, including body weight. We found evidence for positive phenotypic selection on tolerance: on average, individuals who lost weight more slowly with increasing parasite burden had higher lifetime breeding success. This variation did not have an additive genetic basis. These results reveal that selection on tolerance operates under natural conditions. They also support theoretical predictions for the erosion of additive genetic variance of traits under strong directional selection and fixation of genes conferring tolerance. Our findings provide the first evidence of selection on individual tolerance of infection in animals and suggest practical applications in animal and human disease management in the face of highly prevalent parasites.

Figure 1. Mean, population-level tolerance of Soay sheep to gastrointestinal nematodes.

The negative association between body weight and strongyle FEC was estimated from data on 4,934 captures of 2,438 individual sheep. Points show mean body weight for each level of FEC (2,000 =  counts of 2,000 eggs/gram or over) ±1 SE. Plot data are shown in Table S4.

Figure 2. Significant individual-level variation in tolerance of gastrointestinal nematodes by the Soay sheep.

All plots show results of the best-fitting random regression model of tolerance, shown in full in Table 1A. (A) Predicted slopes of the decline in body weight with increasing strongyle FEC for each of the 2,934 individuals in our analyses. Model predictions used for plotting Figure 2A are given in Table S5. Because of the high density of crossing slopes in (A), we also provide (B) a histogram of the distribution of the estimated individual intercepts of body weight (i.e., body weight where FEC = 0) and (C) a histogram of the estimated slopes of individual changes in body weight from 0 to 2,000 eggs/gram of FEC. The most tolerant hosts lose the least weight; the least tolerant lose the most weight. FECs of up to 2,000 represent >98% of the range of parasite burdens experienced by the population. Model estimates used to generate histograms are given in Table S6.

Figure 3. Positive phenotypic selection for increased tolerance in Soay sheep.

(A) Mean relLBS is higher in individuals that were more tolerant of infections. The plot was generated from individual estimates of tolerance slopes and relLBS from the model shown in Table 2. Individuals in the four tolerance quartiles are predicted to lose varying amounts of weight between infection levels of 0 and 2,000 strongyle eggs/gram of faeces, as follows: Q1 =  loss of >2.73 kg; Q2 =  loss of 2.72–2.53 kg; Q3 =  loss of 2.52–2.34 kg; Q4 =  loss of <2.34 kg. Data plotting these estimates are shown in Table S7. (B) Estimated selection gradients calculated from the bivariate model of body weight (WT) and relLBS, which is shown in full in Table 2. Selection gradients were calculated for each of 1,000 posterior estimates of the individual VCV matrix as described in the text for individual variation in body weight; in the slope of body weight on FEC—that is, tolerance; and in the slope of body weight on age. Points show mean estimated selection gradient of each trait on LBS±95% CI. The model estimates used to generate Figure 3B are shown in Table S8.