Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Developmental Plasticity and Evolution. In: Mary Jane West-Eberhard, Editor, Oxford University Press (2003) Pp. xi+794. Price $50.00 paper.

Joseph Pickrell and colleagues analyze genome-wide association data for 42 human phenotypes or diseases and identify several hundred loci influencing multiple traits. They also find several traits with overlapping genetic architectures as well as pairs of traits showing evidence of a causal relationship.

/pdf/detection-and-interpretation-of-shared-genetic-influences-on-48uvfdagn9.pdf

Detection and interpretation of shared genetic influences on 42 human traits

https://discovery.dundee.ac.uk/ws/files/49830502/CANCER_CELL_D_19_01068R3_Text_final._Hayes_et_al.pdf

Oxidative Stress in Cancer.

The search for the alleles that matter, the quantitative trait nucleotides (QTNs) that underlie heritable variation within populations and divergence among them, is a popular pursuit. But what is the question to which QTNs are the answer? Although their pursuit is often invoked as a means of addressing the molecular basis of phenotypic evolution or of estimating the roles of evolutionary forces, the QTNs that are accessible to experimentalists, QTNs of relatively large effect, may be uninformative about these issues if large-effect variants are unrepresentative of the alleles that matter. Although 20th century evolutionary biology generally viewed large-effect variants as atypical, the field has recently undergone a quiet realignment toward a view of readily discoverable large-effect alleles as the primary molecular substrates for evolution. I argue that neither theory nor data justify this realignment. Models and experimental findings covering broad swaths of evolutionary phenomena suggest that evolution often acts via large numbers of small-effect polygenes, individually undetectable. Moreover, these small-effect variants are different in kind, at the molecular level, from the large-effect alleles accessible to experimentalists. Although discoverable QTNs address some fundamental evolutionary questions, they are essentially misleading about many others.

/pdf/the-qtn-program-and-the-alleles-that-matter-for-evolution-20ux8399mc.pdf

The QTN Program and the Alleles That Matter for Evolution: All That’s Gold Does Not Glitter

Cryptic genetic variation (CGV) is invisible under normal conditions, but it can fuel evolution when circumstances change In theory, CGV can represent a massive cache of adaptive potential or a pool of deleterious alleles that are in need of constant suppression CGV emerges from both neutral and selective processes, and it may inform about how human populations respond to change CGV facilitates adaptation in experimental settings, but does it have an important role in the real world? Here, we review the empirical support for widespread CGV in natural populations, including its potential role in emerging human diseases and the growing evidence of its contribution to evolution

Cryptic genetic variation: evolution's hidden substrate

https://www.cell.com/trends/genetics/pdf/S0168-9525(12)00169-2.pdf

The many faces of pleiotropy

Latitudinal clines are widespread in Drosophila melanogaster, and many have been interpreted as adaptive responses to climatic variation. However, the selective mechanisms generating many such patterns remain unresolved, and there is relatively little information regarding how basic life-history components such as fecundity, life span and mortality rates vary across environmental gradients. Here, it is shown that four life-history traits vary predictably with geographic origin of populations sampled along the latitudinal gradient in the eastern United States. Although such patterns are indicative of selection, they cannot distinguish between the direct action of selection on the traits in question or indirect selection by means of underlying genetic correlations. When independent suites of traits covary with geography, it is therefore critical to separate the widespread effects of population source from variation specifically for the traits under investigation. One trait that is associated with variation in life histories and also varies with latitude is the propensity to express reproductive diapause; diapause expression has been hypothesized as a mechanism by which D. melanogaster adults overwinter, and as such may be subject to strong selection in temperate habitats. In this study, recently derived isofemale lines were used to assess the relative contributions of population source and diapause genotype in generating the observed variance for life histories. It is shown that although life span, fecundity and mortality rates varied predictably with geography, diapause genotype explained the majority of the variance for these traits in the sampled populations. Both heat and cold shock resistance were also observed to vary predictably with latitude for the sampled populations. Cold shock tolerance varied between diapause genotypes and the magnitude of this difference varied with geography, whereas heat shock tolerance was affected solely by geographic origin of the populations. These data suggest that a subset of life-history parameters is significantly influenced by the genetic variance for diapause expression in natural populations, and that the observed variance for longevity and fecundity profiles may reflect indirect action of selection on diapause and other correlated traits.

https://bioone.org/journals/evolution/volume-62/issue-5/j.1558-5646.2008.00351.x/Reproductive-Diapause-and-Life-History-Clines-in-North-American-Populations/10.1111/j.1558-5646.2008.00351.x.pdf

Reproductive Diapause and Life-History Clines in North American Populations of Drosophila melanogaster

Life history traits are critical components of fitness and frequently reflect adaptive responses to environmental pressures. However, few genes that contribute to natural life history variation have been identified. Insulin signalling mediates the determination of life history traits in many organisms, and single gene manipulation in Drosophila melanogaster suggests that individual genes in the pathway have the potential to produce major effects on these quantitative traits. We evaluated allelic variation at two insulin signalling genes, the Insulin-like Receptor (InR) and its substrate, chico, in natural populations of D. melanogaster. We found different patterns of variation: InR shows evidence of positive selection and clines in allele frequency across latitude; chico exhibits neutral patterns of evolution. The clinal patterns at InR are replicated between North America and Australia, showing striking similarity in the distribution of specific alleles and the rate at which allele frequencies change across latitude. Moreover, we identified a polymorphism at InR that appears to be functionally significant and consistent with hypothetical patterns of selection across geography. This polymorphism provides new characterization of genic regions of functionality within InR, and is likely a component in a suite of genes and traits that respond adaptively to climatic variation.

Identification of a candidate adaptive polymorphism for Drosophila life history by parallel independent clines on two continents

The dipteran Drosophila melanogaster can express a form of reproductive quiescence or diapause when exposed to low temperature and shortened photoperiod. Among natural populations in the eastern United States, the frequency of lines that express reproductive diapause in the laboratory varies substantially and predictably with latitudinal origin. The goals of the present study were twofold: (1) to examine the impact of genetic variance for diapause expression on multiple traits associated with organismal fitness; and (2) to evaluate the potential for fitness trade-offs between diapause and nondiapause phenotypes that may result in the observed cline. Even prior to diapause entry or expression, inbred lines that express and do not express reproductive diapause in laboratory assays were constitutively distinct for life span, age-specific mortality rates, fecundity profiles, resistance to cold and starvation stress, lipid content, development time, and egg-to-adult viability. Furthermore, estimates of genetic correlations based on line means revealed significant differentiation for genetic variance/covariance matrices between diapause and nondiapause lines. The data indicate the potential for life-history trade-offs associated with variation for the diapause phenotype. The observed cline in diapause incidence in the eastern United States may be generated by these trade- offs and the associated spatial and/or temporal variation in relative fitness of these two phenotypes in natural popu- lations.

Annalise B. Paaby

Papers

Cryptic genetic variation: evolution's hidden substrate

The many faces of pleiotropy

Reproductive Diapause and Life-History Clines in North American Populations of Drosophila melanogaster

Identification of a candidate adaptive polymorphism for Drosophila life history by parallel independent clines on two continents

Genetic variance for diapause expression and associated life histories in Drosophila melanogaster