Jake Gratten

Historical information can be used, in addition to pedigree, traits and genotypes, to map quantitative trait locus (QTL) in general populations via maximum likelihood estimation of variance components. This analysis is known as linkage disequilibrium (LD) and linkage mapping, because it exploits both linkage in families and LD at the population level. The search for QTL in the wild population of Soay sheep on St. Kilda is a proof of principle. We analysed the data from a previous study and confirmed some of the QTLs reported. The most striking result was the confirmation of a QTL affecting birth weight that had been reported using association tests but not when using linkage-based analyses.

Understanding the maintenance of genetic variation in natural populations is a core aim of evolutionary genetics. Insight can be gained by quantifying selection at the level of the genotype, as opposed to the phenotype. Here, we show that in a natural population of Soay sheep which is polymorphic for coat pattern, recessive genetic variants at the causal gene, agouti signalling protein (ASIP) are associated with reduced lifetime fitness. This was due primarily to a reduction in juvenile survival of uniformly coloured (self-type) sheep, which are homozygous recessive, and occurs despite significantly higher reproductive success in surviving self-type adults. Consistent with their relatively low fitness, we show that the frequency of self-type individuals has declined from 1985 to 2008. Remarkably though, the frequency of the underlying self-allele has increased, because the frequency of heterozygous individuals (who harbour the majority of all self-alleles) has increased. Indeed, the ratio of observed/expected heterozygous individuals has increased during the study, such that there is now a significant excess of heterozygotyes. By employing gene-dropping simulations, we show that microevolutionary trends in the frequency and excess of ASIP heterozygotes are too pronounced to be caused by genetic drift. Studying this polymorphism at the level of phenotype rather than underlying genotype would have failed to detect cryptic fitness differences. We would also have been unable to rule out genetic drift as an evolutionary force driving genetic change. This highlights the importance of resolving the underlying genetic basis of phenotypic variation in explaining evolutionary dynamics.

Over the past decade, long-term studies of vertebrate populations have been the focus of many quantitative genetic studies. As a result, we have a clearer understanding of why some fitness-related traits are heritable and under selection, but are apparently not evolving. An exciting extension of this work is to identify the genes underlying phenotypic variation in natural populations. The advent of next-generation sequencing and high-throughput single nucleotide polymorphism (SNP) genotyping platforms means that mapping studies are set to become widespread in those wild populations for whom appropriate phenotypic data and DNA samples are available. Here, we highlight the progress made in this area and define evolutionary genetic questions that have become tractable with the arrival of these new genomics technologies.