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Biomedical subjects

W K Potts

Publications and source records attributed to W K Potts.

16 recordsLinked to original sources
PubMed2001

Size and fluctuating asymmetry of morphometric characters in mice: their associations with inbreeding and t-haplotype.

Fluctuating asymmetry (FA), a ubiquitous type of asymmetry of bilateral characters, often has been used as a measure of developmental instability in populations. FA is expected to increase in populations subjected to genetic stressors such as inbreeding or environmental stressors such as toxins or parasites, although results have not always been consistent. We tested whether FA in four skeletal size characters and mandible shape was greater in a population of wild-derived mice reared in the laboratory and subjected to one generation of inbreeding (F = 0.25) versus that in an outbred group (F = 0.00). FA did not significantly differ between the inbred and outbred groups, despite the fact that these two groups differed dramatically in fitness under seminatural population conditions. As far as we know, this is the first study to evaluate the relationship between FA and inbreeding in wild house mice, and our general conclusion is opposite that of earlier work on laboratory inbred strains of mice and their hybrids. Size for two of the characters was significantly less in inbreds than in outbreds, however, and there was a significant difference between inbreds and outbreds in the signed differences of right and left sides in one character (humerus length). Some of the mice in both groups also were heterozygous or homozygous carriers of the t-complex. Because mice carrying this chromosome 17 variant are known to have reduced fitness, we also tested whether they had greater FA than mice carrying non-t-haplotypes. The overall level of a composite FA index calculated from all four characters was in fact significantly higher in the t-bearing mice. These combined results suggest that FA is not a generally sensitive proxy measure for fitness, but can be associated with fitness reductions for certain genetic stressors.

Analysis of Variance↗
PubMed2001

Accumulated background variation among H2 mutant congenic strains: elimination through PCR-based genotyping of F2 segregants.

Many commercially and privately available congenic strains of laboratory animals were founded decades ago and are likely to differ from one another by dozens of fixed mutational differences at background loci. This problem is often ignored despite growing evidence that such background variation exists. Eliminating this confounding variation can be largely accomplished by crossing congenic strains to produce F2 segregants that are homozygous (or heterozygous) for relevant genes. Discriminating F2 homozygotes can be difficult when strain differences are minor, as are mutant mouse strains differing at single major histocompatibility loci (H2 mutant congenics). Here, we describe a two-step polymerase chain reaction (PCR) method utilizing heteroduplex analysis and sequence specific primers (SSP-PCR) that efficiently discriminates the F2 progeny of two such H2 mutant congenic mice crosses (bm1xB6 and bm1xbm3). A third H2 mutant cross cannot be resolved by heteroduplexing, but is discriminated (albeit less efficiently) with SSP-PCR alone. This sensitive application can be extended to any congenic mutant strains.

Alleles↗
PubMed2000

Male-male competition magnifies inbreeding depression in wild house mice.

The detrimental effects of inbreeding on vertebrates are well documented for early stages of the life cycle in the laboratory. However, the consequences of inbreeding on long-term survival and reproductive success (Darwinian fitness) are uncertain for vertebrates in the wild. Here, we report direct experimental evidence for vertebrates that competition increases the harmful effects of inbreeding on offspring survival and reproduction. We compared the fitness of inbred (from full-sib matings) and outbred wild house mice (Mus domesticus) in large, seminatural enclosures. Inbred males sired only one-fifth as many surviving offspring as outbred males because of their poor competitive ability and survivorship. In laboratory conditions, inbreeding had relatively minor effects on male reproductive success and no effect on survivorship. Seminatural conditions did not increase inbreeding depression for females, probably because females were not competing for any critical resources. The overall reduction in fitness from inbreeding was 57%, which is 4.5 times as great as previous estimates from the laboratory. These results have important implications for medicine, conservation, evolutionary biology, and functional genomics.

Animals↗
PubMed1998

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).

Animals↗
PubMed1997

A microsatellite-based MHC genotyping system for house mice (Mus domesticus).

Major histocompatibility complex (MHC) genes are the most polymorphic loci known for vertebrates. Although this has been known for over two decades, the selective forces maintaining this genetic diversity are unclear. Efforts to study selection on these loci in nature have been hampered because no simple MHC typing systems are available. Here, we describe and evaluate a microsatellite-based MHC genotyping system for house mice (Mus domesticus). Thirty-five MHC-linked microsatellite loci were tested for amplification and scoring reliability, and 21 were deemed useful. These 21 loci were efficient at discriminating among nine serologically distinct MHC haplotypes, with 52% of microsatellite pairs providing 100% resolution. Since these microsatellite loci are scattered across the entire MHC region, they will be effective at detecting recombinant haplotypes. The number of alleles is higher for microsatellites inside the MHC than outside it, which presumably reflects genetic hitchhiking with MHC alleles under balancing selection. This microsatellite typing system now allows testing hypotheses about the nature of selection operating on MHC genes in natural populations of M. domesticus and other murid rodent species.

Alleles↗
PubMed1997

The nature of selection on the major histocompatibility complex.

Only natural selection can account for the extreme genetic diversity of genes of the major histocompatibility complex (MHC). Although the structure and function of classic MHC genes is well understood at the molecular and cellular levels, there is controversy about how MHC diversity is selectively maintained. The diversifying selection can be driven by pathogen interactions and inbreeding avoidance mechanisms. Pathogen-driven selection can maintain MHC polymorphism based on heterozygote advantage or frequency-dependent selection due to pathogen evasion of MHC-dependent immune recognition. Empirical evidence demonstrates that specific MHC haplotypes are resistant to certain infectious agents, while susceptible to others. These data are consistent with both heterozygote advantage and frequency-dependent models. Additional research is needed to discriminate between these mechanisms. Infectious agents can precipitate autoimmunity and can potentially contribute to MHC diversity through molecular mimicry and by favoring immunodominance. MHC-dependent abortion and mate choice, based on olfaction, can also maintain MHC diversity and probably functions both to avoid genome-wide inbreeding and produce MHC-heterozygous offspring with increased immune responsiveness. Although this diverse set of hypotheses are often treated as competing alternatives, we believe that they all fit into a coherent, internally consistent thesis. It is likely that at least in some species, all of these mechanisms operate, leading to the extreme diversification found in MHC genes.

Animals↗
PubMed1995

Contrasting histories of avian and mammalian Mhc genes revealed by class II B sequences from songbirds.

To explore the evolutionary dynamics of genes in the major histocompatibility complex (Mhc) in nonmammalian vertebrates, we have amplified complete sequences of the polymorphic second (beta1) and third (beta2) exons of class II beta chain genes of songbirds. The pattern of nucleotide substitution in the antigen-binding site of sequences cloned from three behaviorally and phylogenetically divergent songbirds [scrub jays Aphelocoma coerulescens), red-winged blackbirds (Agelaius phoeniceus), and house finches (Carpodacus mexicanus) reveals that class II B genes of songbirds are subject to the same types of diversifying forces as those observed at mammalian class II loci. By contrast, the tree of avian class II B genes reveals that orthologous relationships have not been retained as in placental mammals and that, unlike class II genes in mammals, genes in songbirds and chickens have had very recent common ancestors within their respective groups. Thus, whereas the selective forces diversifying class II B genes of birds are likely similar to those in mammals, their long-term evolutionary dynamics appear to be characterized by much higher rates of concerted evolution.

Amino Acid Sequence↗
PubMed1995

Dynamics of Mhc evolution in birds and crocodilians: amplification of class II genes with degenerate primers.

Genes of the major histocompatibility complex (Mhc) are the most polymorphic functional loci in mammalian populations, but little is known of Mhc variability in natural populations of nonmammalian vertebrates. To help extend such studies to birds and relatives, we present a pair of degenerate primers that amplify polymorphic segments of one chain (the beta chain) of the class II genes from the major histocompatibility complex (Mhc) of archosaurs (birds+crocodilians). The primers target two conserved regions lying within portions of the antigen-binding site (ABS) encoded by the second exon and amplify multiple genes from both genomic DNA and cDNA. The pattern of nucleotide substitution in ABS codons of 51 sequences amplified and cloned from five species of passerine birds and an alligator (Alligator mississippiensis) indicates that archosaurian class II beta genes are subject to selective forces similar to those operating in mammalian populations. Hybridization of a genomic clone generated by the primers revealed highly polymorphic bands in a sample of Florida scrub jays (Aphelocoma coerulescens coerulescens). Because the primers amplify only part of the ABS from multiple class II genes, they will be useful primarily for generating species specific clones, thereby providing a critical inroad to more detailed structural and evolutionary studies.

Alligators and Crocodiles↗
PubMed1995

Pathogen-based models favoring MHC genetic diversity.

We present six models that are currently the most likely ways that pathogens might favor the evolution of MHC genetic diversity. Although each model makes one or more unique predictions, the current lack of crucial data prevents distinguishing the relative importance of each model. However, this first-time organization of these models should contribute to the design of critical experiments. This synthetic review yields at least three essentially new ideas. First, MHC-dependent immune recognition may be sufficiently redundant to render it essentially escape-proof by pathogens. Second, the four models based on pathogen escape do not work (or work weakly) for diversifying class II genes, unless class II-restricted cytotoxic T-cells are important, an idea that is controversial. Third, pathogen-escape events have traditionally been thought to result in only frequency-dependent selection but here we show that heterozygote advantage is an inevitable consequence of such pathogen evasion. Therefore, the controversy over the relative importance of these two forms of balancing selection is largely a false dichotomy.

Animals↗
PubMed1994

The role of infectious disease, inbreeding and mating preferences in maintaining MHC genetic diversity: an experimental test.

In house mice, and probably most mammals, major histocompatibility complex (MHC) gene products influence both immune recognition and individual odours in an allele-specific fashion. Although it is generally assumed that some form of pathogen-driven balancing selection is responsible for the unprecedented genetic diversity of MHC genes, the MHC-based mating preferences observed in house mice are sufficient to account for the genetic diversity of MHC genes found in this and other vertebrates. These MHC disassortative mating preferences are completely consistent with the conventional view that pathogen-driven MHC heterozygote advantage operates on MHC genes. This is because such matings preferentially produce MHC-heterozygours progeny, which could enjoy enhanced disease resistance. However, such matings could also function to avoid genome-wide inbreeding. To discriminate between these two hypotheses we measured the fitness consequences of both experimentally manipulated levels of inbreeding and MHC homozygosity and heterozygosity in semi-natural populations of wild-derived house mice. We were able to measure a fitness decline associated with inbreeding, but were unable to detect fitness declines associated with MHC homozygosity. These data suggest that inbreeding avoidance may be the most important function of MHC-based mating preferences and therefore the fundamental selective force diversifying MHC genes in species with such mating patterns. Although controversial, this conclusion is consistent with the majority of the data from the inbreeding and immunological literature.

Animals↗
PubMed1994

Cooperative display and relatedness among males in a lek-mating bird.

Long-tailed manakins mate in leks and cooperate in multiyear male-male partnerships. An alpha male is responsible for virtually all mating, whereas a beta male assists in the courtship displays. Such altruism by the beta male poses a problem for evolutionary theory because most theoretical treatments and empirical examples of cooperative behavior involve kin selection or reciprocity. Here it is shown that alpha and beta partners are not relatives and that reciprocity is not involved. Instead, direct, though long-delayed benefits to beta males are demonstrated, which include rare copulations, ascension to alpha status, and female lek fidelity. These benefits maintain this unusual form of male-male cooperation.

Alleles↗
PubMed1993

Evolution of MHC genetic diversity: a tale of incest, pestilence and sexual preference.

Evidence from the house mouse (Mus) suggests that the extreme diversity of genes of the major histocompatibility complex (MHC) results from three different forms of selection involving infectious disease (pestilence), inbreeding (incest) and MHC-based mating (sexual) preferences. MHC-based disassortative mating preferences are presumed to have evolved because they reduce homozygosity throughout the genome, and particularly within loci linked to the MHC. Progeny derived from such disassortative matings would enjoy increased fitness because of both reduced levels of inbreeding depression and increased resistance to infectious disease arising from their increased MHC heterozygosity.

Animals↗
PubMed1992

Communal nesting patterns in mice implicate MHC genes in kin recognition.

House mice (Mus musculus domesticus) form communal nests and appear to nurse each other's pups indiscriminately. Communal nesting probably functions to reduce infanticide, but it also makes females vulnerable to exploitation if nursing partners fail to provide their fair share of care. Kinship theory predicts that females will preferentially form communal nests with relatives to minimize exploitation and further increase inclusive fitness. Here we provide evidence from seminatural populations that females prefer communal nesting partners that share allelic forms of major histocompatibility complex genes. Such behaviour would lead to the selection of close relatives as communal nesting partners. Although criteria for the demonstration of kin recognition are currently embroiled in controversy, this is the first vertebrate study to meet Grafen's restrictive requirements: discrimination is based on genetic similarity at highly polymorphic loci, incidental correlations due to relatedness are experimentally controlled, and strong reasons exist for expecting the assayed behaviour to be kin-selected.

Animals↗
PubMed1991

Mating patterns in seminatural populations of mice influenced by MHC genotype.

Because of the central role of major histocompatibility complex (MHC) genes in immune recognition, it is often assumed that parasite-driven selection maintains the unprecendented genetic diversity of these genes. But associations between MHC genotype and specific infectious diseases have been difficult to identify with a few exceptions such as Marek's disease and malaria. Alternatively, MHC-related reproductive mechanisms such as selective abortion and mating preferences could be responsible for the diversity. To determine both the nature and strength of selection operating on MHC genes by we have studied components of selection in seminatural populations of mice (Mus musculus domesticus). Here we assess MHC-related patterns of reproduction and early (preweaning) mortality by analysing 1,139 progeny born in nine populations, and 662 progeny from laboratory matings. Reproductive mechanisms, primarily mating preferences, result in 27% fewer MHC-homozygous offspring than expected from random mating. MHC genotype had no detectable influence on neonatal (preweaning) mortality. These mating preferences are strong enough to account for most of the MHC genetic diversity found in natural populations of Mus.

Animals↗