Dustin J. Penn

The evolution of mating preferences and major histocompatibility complex genes

House mice prefer mates genetically dissimilar at the major histocompatibility complex (MHC). The highly polymorphic MHC genes control immunological self/nonself recognition; therefore, this mating preference may function to provide “good genes” for an individuals offspring. However, the evidence for MHC‐dependent mating preferences is controversial, and its function remains unclear. Here we provide a critical review of the studies on MHC‐dependent mating preferences in mice, sheep, and humans and the possible functions of this behavior. There are three adaptive hypotheses for MHC‐dependent mating preferences. First, MHC‐disassortative mating preferences produce MHC‐heterozygous offspring that may have enhanced immunocompetence. Although this hypothesis is not supported by tests of single parasites, MHC heterozygotes may be resistant to multiple parasites. Second, we propose that MHC‐dependent mating preferences enable hosts to provide a “moving target” against rapidly evolving parasites that escape immune recognition (the Red Queen hypothesis). Such parasites are suspected to drive MHC diversity through rare‐allele advantage. Thus, the two forms of parasite‐mediated selection thought to drive MHC diversity, heterozygote and rare‐allele advantage, will also favor MHC‐dependent mating preferences. Finally, MHC‐dependent mating preferences may also function to avoid inbreeding; a hypothesis consistent with other evidence that MHC genes play a role in kin recognition.

MHC heterozygosity confers a selective advantage against multiple-strain infections

Genetic heterozygosity is thought to enhance resistance of hosts to infectious diseases, but few tests of this idea exist. In particular, heterozygosity at the MHC, the highly polymorphic loci that control immunological recognition of pathogens, is suspected to confer a selective advantage by enhancing resistance to infectious diseases (the “heterozygote advantage” hypothesis). To test this hypothesis, we released mice into large population enclosures and challenged them with multiple strains of Salmonella and one of Listeria. We found that during Salmonella infections with three avirulent strains, MHC heterozygotes had greater survival and weight than homozygotes (unlike sham controls), and they were more likely to clear chronic Salmonella infection than homozygotes. In laboratory experiments, we found that MHC heterozygosity enhanced the clearance of multiple-strain Salmonella infections. Yet, contrary to what is widely assumed, the benefits of heterozygosity were due to resistance being dominant rather than overdominant, i.e., heterozygotes were more resistant than the average of parental homozygotes, but they were not more resistant than both. The fact that MHC heterozygotes were more resistant to infection and had higher fitness than homozygotes provides a functional explanation for MHC-disassortative mating preferences.

Chemical signals and parasite-mediated sexual selection

Research into visual and acoustic signals has demonstrated that exaggerated sexual displays often provide an honest indicator of a males resistance to parasites. Recent studies with rodents and humans now suggest that chemosensory signals also reveal a males disease resistance and his genetic compatibility. Our understanding of sexual selection has been greatly enriched by considering the mechanisms underlying visual and acoustic displays, and recent advances in chemical communication will help to determine what kind of information is revealed by an individuals scent.

Individual and gender fingerprints in human body odour

Individuals are thought to have their own distinctive scent, analogous to a signature or fingerprint. To test this idea, we collected axillary sweat, urine and saliva from 197 adults from a village in the Austrian Alps, taking five sweat samples per subject over 10 weeks using a novel skin sampling device. We analysed samples using stir bar sorptive extraction in connection with thermal desorption gas chromatograph–mass spectrometry (GC–MS), and then we statistically analysed the chromatographic profiles using pattern recognition techniques. We found more volatile compounds in axillary sweat than in urine or saliva, and among these we found 373 peaks that were consistent over time (detected in four out of five samples per individual). Among these candidate compounds, we found individually distinct and reproducible GC–MS fingerprints, a reproducible difference between the sexes, and we identified the chemical structures of 44 individual and 12 gender-specific volatile compounds. These individual compounds provide candidates for major histocompatibility complex and other genetically determined odours. This is the first study on human axillary odour to sample a large number of subjects, and our findings are relevant to understanding the chemical nature of human odour, and efforts to design electronic sensors (e-nose) for biometric fingerprinting and disease diagnoses.

MHC-disassortative mating preferences reversed by cross-fostering.

House mice (Mus musculus domesticus) avoid mating with individuals that are genetically similar at the major histocompatibility complex (MHC). Mice are able recognize MHC–similar individuals through specific odour cues. However, to mate disassortatively for MHC genes, individuals must have a referent, either themselves (self–inspection) or close kin (familial imprinting), with which to compare the MHC identity of potential mates. Although studies on MHC–dependent mating preferences often assume that individuals use self–inspection, laboratory experiments with male mice indicate that they use familial imprinting, i.e. males learn the MHC identity of their family and then avoid mating with females carrying ‘familial’ MHC alleles. To determine if female mice use familial imprinting, we cross–fostered wild–derived female mouse pups into MHC–dissimilar families, and then tested if this procedure reversed their mating preferences compared with in–fostered controls. Our observations of the females mating behaviour in seminatural social conditions and the genetic typing of their progeny both indicated that females avoided mating with males carrying MHC genes of their foster family, supporting the familial imprinting hypothesis. We show that MHC–dependent familial imprinting potentially provides a more effective mechanism for avoiding kin matings and reducing inbreeding than self–inspection.

Major histocompatibility complex heterozygote superiority during coinfection.

ABSTRACT Genes of the major histocompatibility complex (MHC) play a critical role in immune recognition, and many alleles confer susceptibility to infectious and autoimmune diseases. How these deleterious alleles persist in populations is controversial. One hypothesis postulates that MHC heterozygote superiority emerges over multiple infections because MHC-mediated resistance is generally dominant and many allele-specific susceptibilities to pathogens will be masked by the resistant allele in heterozygotes. We tested this hypothesis by using experimental coinfections with Salmonella enterica (serovar Typhimurium C5TS) and Theilers murine encephalomyelitis virus (TMEV) in MHC-congenic mouse strains where one haplotype was resistant to Salmonella and the other was resistant to TMEV. MHC heterozygotes were superior to both homozygotes in 7 out of 8 comparisons (P = 0.0024), and the mean standardized pathogen load of heterozygotes was reduced by 41% over that of homozygotes (P = 0.01). In contrast, no heterozygote superiority was observed when the MHC haplotype combinations had similar susceptibility profiles to the two pathogens. This is the first experimental evidence for MHC heterozygote superiority against multiple pathogens, a mechanism that would contribute to the evolution of MHC diversity and explain the persistence of alleles conferring susceptibility to disease.

Stress impacts telomere dynamics

Telomeres are DNA–protein complexes at the ends of chromosomes that control genomic integrity but appear to become shorter with age and stress. To test whether stress causes telomere attrition, we exposed the offspring of wild-caught house mice (Mus musculus) to stressful conditions and examined the changes in telomere length over six months. We found that females exposed to males and reproductive stress (either with or without crowding) had significantly shorter telomeres than controls, and males exposed to crowding stress had shorter telomeres than males that were not crowded. Our results indicate that stress alters telomere dynamics, causing attrition and hindering restoration, and these effects are sex dependent. Telomeres may thus provide a biomarker for assessing an individuals cumulative exposure or ability to cope with stressful conditions.

Telomere Attrition Due to Infection

Background Telomeres–the terminal caps of chromosomes–become shorter as individuals age, and there is much interest in determining what causes telomere attrition since this process may play a role in biological aging. The leading hypothesis is that telomere attrition is due to inflammation, exposure to infectious agents, and other types of oxidative stress, which damage telomeres and impair their repair mechanisms. Several lines of evidence support this hypothesis, including observational findings that people exposed to infectious diseases have shorter telomeres. Experimental tests are still needed, however, to distinguish whether infectious diseases actually cause telomere attrition or whether telomere attrition increases susceptibility to infection. Experiments are also needed to determine whether telomere erosion reduces longevity. Methodology/Principal Findings We experimentally tested whether repeated exposure to an infectious agent, Salmonella enterica, causes telomere attrition in wild-derived house mice (Mus musculus musculus). We repeatedly infected mice with a genetically diverse cocktail of five different S. enterica strains over seven months, and compared changes in telomere length with sham-infected sibling controls. We measured changes in telomere length of white blood cells (WBC) after five infections using a real-time PCR method. Our results show that repeated Salmonella infections cause telomere attrition in WBCs, and particularly for males, which appeared less disease resistant than females. Interestingly, we also found that individuals having long WBC telomeres at early age were relatively disease resistant during later life. Finally, we found evidence that more rapid telomere attrition increases mortality risk, although this trend was not significant. Conclusions/Significance Our results indicate that infectious diseases can cause telomere attrition, and support the idea that telomere length could provide a molecular biomarker for assessing exposure and ability to cope with infectious diseases.

Untrained mice discriminate MHC-determined odors

Immune recognition occurs when foreign antigens are presented to T-lymphocytes by molecules encoded by the highly polymorphic genes of the major histocompatibility complex (MHC). House mice (Mus musculus) prefer to mate with individuals that have dissimilar MHC genes. Numerous studies indicate that mice recognize MHC identity through chemosensory cues; however, it is unclear whether odor is determined by classical, antigen-presenting MHC loci or closely linked genes. Previous studies have relied on training laboratory mice and rats to distinguish MHC-associated odors, but there are several reasons why training experiments may be inappropriate assays for testing if MHC genes affect odor. The aim of this study was to determine whether classical MHC genes affect individual odors and whether wild-derived mice can detect MHC-associated odors without training. In the first experiment, we found that wild-derived mice can be trained in a Y-maze to detect the odors of mice that differ genetically only in the MHC region. In the second and third experiments, we used a naturalistic habituation assay and found that wild-derived mice can, without training, distinguish the odors of mice that differ genetically only at one classical MHC locus (dm2 mutants).

The Evolutionary Roots of Our Environmental Problems: Toward a Darwinian Ecology

It is widely acknowledged that we need to stabilize population growth and reduce our environmental impact; however, there is little consensus about how we might achieve these changes. Here I show how evolutionary analyses of human behavior provide important, though generally ignored, insights into our environmental problems. First, I review increasing evidence that Homo sapiens has a long history of causing ecological problems. This means that, contrary to popular belief, our species’ capacity for ecological destruction is not simply due to “Western” culture. Second, I provide an overview of how evolutionary research can help to understand why humans are ecologically destructive, including the reasons why people often overpopulate, overconsume, exhaust common‐pool resources, discount the future, and respond maladaptively to modern environmental hazards. Evolutionary approaches not only explain our darker sides, they also provide insights into why people cherish plants and animals and often support environmental and conservation efforts (e.g., Wilson’s “biophilia hypothesis”). Third, I show how evolutionary analyses of human behavior offer practical implications for environmental policy, education, and activism. I suggest that education is necessary but insufficient because people also need incentives. Individual incentives are likely to be the most effective, but these include much more than narrow economic interests (e.g., they include one’s reputation in society). Moralizing and other forms of social pressure used by environmentalists to bring about change appear to be effective, but this idea needs more research. Finally, I suggest that integrating evolutionary perspectives into the environmental sciences will help to break down the artificial barriers that continue to divide the biological and social sciences, which unfortunately obstruct our ability to understand ourselves and effectively address our environmental problems.