scholarly journals Host-pathogen coevolution increases genetic variation in susceptibility to infection

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Elizabeth ML Duxbury ◽  
Jonathan P Day ◽  
Davide Maria Vespasiani ◽  
Yannik Thüringer ◽  
Ignacio Tolosana ◽  
...  

It is common to find considerable genetic variation in susceptibility to infection in natural populations. We have investigated whether natural selection increases this variation by testing whether host populations show more genetic variation in susceptibility to pathogens that they naturally encounter than novel pathogens. In a large cross-infection experiment involving four species of Drosophila and four host-specific viruses, we always found greater genetic variation in susceptibility to viruses that had coevolved with their host. We went on to examine the genetic architecture of resistance in one host species, finding that there are more major-effect genetic variants in coevolved host-pathogen interactions. We conclude that selection by pathogens has increased genetic variation in host susceptibility, and much of this effect is caused by the occurrence of major-effect resistance polymorphisms within populations.

2018 ◽  
Author(s):  
Elizabeth ML Duxbury ◽  
Jonathan P Day ◽  
Davide Maria Vespasiani ◽  
Yannik Thüringer ◽  
Ignacio Tolosana ◽  
...  

AbstractIt is common to find considerable genetic variation in susceptibility to infection in natural populations. We have investigated whether natural selection increases this variation by testing whether host populations show more genetic variation in susceptibility to pathogens that they naturally encounter than novel pathogens. In a large cross-infection experiment involving four species of Drosophila and four host-specific viruses, we always found greater genetic variation in susceptibility to viruses that had coevolved with their host. We went on to examine the genetic architecture of resistance in one host species, finding that there are more major-effect genetic variants in coevolved host-parasite interactions. We conclude that selection by pathogens increases genetic variation in host susceptibility, and much of this effect is caused by the occurrence of major-effect resistance polymorphisms within populations.


1995 ◽  
Vol 25 (12) ◽  
pp. 2010-2021 ◽  
Author(s):  
Chang-Yi Xie ◽  
Cheng C. Ying

The genetic architecture and adaptive landscape of interior lodgepole pine (Pinuscontorta ssp. latifolia Engelm. ex S. Wats.) in Canada were investigated in a provenance–family plantation located in central British Columbia. Fifty-three natural populations were sampled from three geographic regions covering the entire Canadian range, and their performance in growth and survival was recorded periodically over 20 years. Test results indicate that genetic variation among regions and among populations within regions was highly significant in all the traits investigated and accounted for, respectively, 53% and 41% of the total genetic variation in growth and 41% and 54% in survival. Within-population variation was also significant in growth but not in survival. Interior lodgepole pine in the central region demonstrated less genetic variation than in the northern and southern regions at both the population and family levels. In addition, the proportion of genetic variation associated with population was lower in the central region than in the other regions. Population differentiation in both growth and survival showed discernible elevational and geographic patterns. Regression models describing these adaptive patterns accounted for more than 80% of the among-population variation, and their veracity was verified with independent data. Populations of northern, coastal–interior transition, and high-elevation origin tended to have smaller trees with higher mortality. However, the patterns were not linear but differed in slope and (or) direction among regions. The adaptedness of populations tended to decrease as they were farther away from their origin, with a few exceptions displaying broad adaptation across more than 3° of latitude. As the test proceeded, population differentiation became more evident and adaptive clines became steeper. Some practical implications of these findings have been discussed.


2010 ◽  
Vol 277 (1698) ◽  
pp. 3317-3325 ◽  
Author(s):  
Chris R. Feldman ◽  
Edmund D. Brodie ◽  
Edmund D. Brodie ◽  
Michael E. Pfrender

Detailing the genetic basis of adaptive variation in natural populations is a first step towards understanding the process of adaptive evolution, yet few ecologically relevant traits have been characterized at the genetic level in wild populations. Traits that mediate coevolutionary interactions between species are ideal for studying adaptation because of the intensity of selection and the well-characterized ecological context. We have previously described the ecological context, evolutionary history and partial genetic basis of tetrodotoxin (TTX) resistance in garter snakes ( Thamnophis ). Derived mutations in a voltage-gated sodium channel gene (Na v 1.4) in three garter snake species are associated with resistance to TTX, the lethal neurotoxin found in their newt prey ( Taricha ). Here we evaluate the contribution of Na v 1.4 alleles to TTX resistance in two of those species from central coastal California. We measured the phenotypes (TTX resistance) and genotypes (Na v 1.4 and microsatellites) in a local sample of Thamnophis atratus and Thamnophis sirtalis . Allelic variation in Na v 1.4 explains 23 per cent of the variation in TTX resistance in T. atratus while variation in a haphazard sample of the genome (neutral microsatellite markers) shows no association with the phenotype. Similarly, allelic variation in Na v 1.4 correlates almost perfectly with TTX resistance in T. sirtalis , but neutral variation does not. These strong correlations suggest that Na v 1.4 is a major effect locus. The simple genetic architecture of TTX resistance in garter snakes may significantly impact the dynamics of phenotypic coevolution. Fixation of a few alleles of major effect in some garter snake populations may have led to the evolution of extreme phenotypes and an ‘escape’ from the arms race with newts.


Genetics ◽  
1999 ◽  
Vol 151 (3) ◽  
pp. 1081-1091 ◽  
Author(s):  
Greg Gibson ◽  
Matthew Wemple ◽  
Sylvie van Helden

Abstract Introgression of homeotic mutations into wild-type genetic backgrounds results in a wide variety of phenotypes and implies that major effect modifiers of extreme phenotypes are not uncommon in natural populations of Drosophila. A composite interval mapping procedure was used to demonstrate that one major effect locus accounts for three-quarters of the variance for haltere to wing margin transformation in Ultrabithorax flies, yet has no obvious effect on wild-type development. Several other genetic backgrounds result in enlargement of the haltere significantly beyond the normal range of haploinsufficient phenotypes, suggesting genetic variation in cofactors that mediate homeotic protein function. Introgression of Antennapedia produces lines with heritable phenotypes ranging from almost complete suppression to perfect antennal leg formation, as well as transformations that are restricted to either the distal or proximal portion of the appendage. It is argued that the existence of “potential” variance, which is genetic variation whose effects are not observable in wild-type individuals, is a prerequisite for the uncoupling of genetic from phenotypic divergence.


2008 ◽  
Vol 4 (2) ◽  
pp. 228-231 ◽  
Author(s):  
Gordon Luikart ◽  
Kristy Pilgrim ◽  
Judy Visty ◽  
Vanessa O Ezenwa ◽  
Michael K Schwartz

The loss of genetic variation in host populations is thought to increase host susceptibility to parasites. However, few data exist to test this hypothesis in natural populations. Bighorn sheep ( Ovis canadensis ) populations occasionally suffer disease-induced population declines, allowing us to test for the associations between reduced genetic variation and parasitism in this species. Here, we show that individual mean heterozygosity for 15 microsatellite loci is associated with lungworm abundance ( Protostrongylus spp.) in a small, recently bottlenecked population of bighorn sheep (linear regression, r 2 =0.339, p =0.007). This association remains significant for seven microsatellites located in genes ( p =0.010), but not for eight neutral microsatellites ( p =0.306). Furthermore, heterozygotes at three of four microsatellites located within disease-related genes had lower lungworm burdens. This study corroborates theoretical findings that increased parasitism and disease may be a consequence of reduced heterozygosity in wild populations, and that certain individual loci influence parasite resistance. The results illustrate the usefulness of using genomic information, strong candidate genes and non-invasive sampling for monitoring both genetic variation and fitness-related traits, such as parasite resistance, in natural populations.


Author(s):  
Aleeza C. Gerstein ◽  
Nathaniel Sharp

Ploidy is a significant type of genetic variation, describing the number of chromosome sets per cell. Ploidy evolves in natural populations, clinical populations, and lab experiments, particularly in fungi. Despite a long history of theoretical work on this topic, predicting how ploidy will evolve has proven difficult, as it is often unclear why one ploidy state outperforms another. Here, we review what is known about contemporary ploidy evolution in diverse fungal species through the lens of population genetics. As with typical genetic variants, ploidy evolution depends on the rate that new ploidy states arise by mutation, natural selection on alternative ploidy states, and random genetic drift. However, ploidy variation also has unique impacts on evolution, with the potential to alter chromosomal stability, the rate and patterns of point mutation, and the nature of selection on all loci in the genome. We discuss how ploidy evolution depends on these general and unique factors and highlight areas where additional experimental evidence is required to comprehensively explain the ploidy transitions observed in the field and the lab.


2017 ◽  
Author(s):  
Chuan Cao ◽  
Rodrigo Cogni ◽  
Vincent Barbier ◽  
Francis M. Jiggins

AbstractIt is common to find that major-effect genes are an important cause of variation in susceptibility to infection. Here we have characterised natural variation in a gene called pastrel that explains over half of the genetic variance in susceptibility to the virus DCV in populations of Drosophila melanogaster. We found extensive allelic heterogeneity, with a sample of seven alleles of pastrel from around the world conferring four phenotypically distinct levels of resistance. By modifying candidate SNPs in transgenic flies, we show that the largest effect is caused by an amino acid polymorphism that arose when an ancestral threonine was mutated to alanine, greatly increasing resistance to DCV. Overexpression of the ancestral susceptible allele provides strong protection against DCV, indicating that this mutation acted to improve an existing restriction factor. The pastrel locus also contains complex structural variation and cis-regulatory polymorphisms altering gene expression. We find that higher expression of pastrel is associated with increased survival after DCV infection. To understand why this variation is maintained in populations, we investigated genetic variation surrounding the amino acid variant that is causing flies to be resistant. We found no evidence of natural selection causing either recent changes in allele frequency or geographical variation in frequency, suggesting that this is an old polymorphism that has been maintained at a stable frequency. Overall, our data demonstrate how complex genetic variation at a single locus can control susceptibility to a virulent natural pathogen.


Author(s):  
Elizabeth ML Duxbury ◽  
Jonathan P Day ◽  
Davide Maria Vespasiani ◽  
Yannik Thüringer ◽  
Ignacio Tolosana ◽  
...  

2017 ◽  
Vol 114 (37) ◽  
pp. E7746-E7755 ◽  
Author(s):  
Monica I. Alvarez ◽  
Luke C. Glover ◽  
Peter Luo ◽  
Liuyang Wang ◽  
Elizabeth Theusch ◽  
...  

Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility toSalmonella entericaserovar Typhi (S. Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitatingSalmonelladocking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility toS. Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulatesSalmonellainvasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.


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