A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.

The McDonald and Kreitman test (MKT) is one of the most powerful and extensively used tests to detect the signature of natural selection at the molecular level. Here, we present the standard and generalized MKT website, a novel website that allows performing MKTs not only for synonymous and nonsynonymous changes, as the test was initially described, but also for other classes of regions and/or several loci. The website has three different interfaces: (i) the standard MKT, where users can analyze several types of sites in a coding region, (ii) the advanced MKT, where users can compare two closely linked regions in the genome that can be either coding or noncoding, and (iii) the multi-locus MKT, where users can analyze many separate loci in a single multi-locus test. The website has already been used to show that selection efficiency is positively correlated with effective population size in the Drosophila genus and it has been applied to include estimates of selection in DPDB. This website is a timely resource, which will presumably be widely used by researchers in the field and will contribute to enlarge the catalogue of cases of adaptive evolution. It is available at http://mkt.uab.es.

Polymorphic inversions are a type of structural variants that are difficult to analyze owing to their balanced nature and the location of breakpoints within complex repeated regions. So far, only a handful of inversions have been studied in detail in humans and current knowledge about their possible functional effects is still limited. However, inversions have been related to phenotypic changes and adaptation in multiple species. In this review, we summarize the evidences of the functional impact of inversions in the human genome. First, given that inversions have been shown to inhibit recombination in heterokaryotes, chromosomes displaying different orientation are expected to evolve independently and this may lead to distinct gene-expression patterns. Second, inversions have a role as disease-causing mutations both by directly affecting gene structure or regulation in different ways, and by predisposing to other secondary arrangements in the offspring of inversion carriers. Finally, several inversions show signals of being selected during human evolution. These findings illustrate the potential of inversions to have phenotypic consequences also in humans and emphasize the importance of their inclusion in genome-wide association studies.