Taking Quantitative Genomics into the Wild

A key goal in studies of ecology and evolution is understanding the causes of phenotypic diversity in nature. Most traits of interest, such as those relating to morphology, life-history, immunity and behaviour are quantitative, and phenotypic variation is driven by the cumulative effects of genetic and environmental variation. The field of quantitative genetics aims to quantify the additive genetic component of this trait variance (i.e. the "heritability"), often with the underlying assumption that trait variance is driven by many loci of infinitesimal effects throughout the genome. This approach allows us to understand the evolutionary potential of natural populations and can be extended to examine the genetic covariation with fitness to predict responses to selection. Therefore, quantitative genetic studies are fundamental to understanding evolution in the wild. Over the last two decades, there has been a wealth of studies investigating trait heritabilities and genetic correlations, but these were initially limited to long-term studies of pedigreed populations or common-garden experiments. However, genomic technologies have since allowed quantitative genetic studies in a more diverse range of wild systems and has increased the opportunities for addressing outstanding questions in ecology and evolution. In particular, genomic studies can uncover the genetic basis of fitness-related quantitative traits, allowing a better understanding of their evolutionary dynamics. We organised this special issue to highlight new work and review recent advances at the cutting edge of "Wild Quantitative Genomics". In this Editorial, we will present some history of wild quantitative genetic and genomic studies, before discussing the main themes in the papers published in this special issue and highlighting the future outlook of this dynamic field.Comment: 17 page (plus references) Editorial for a special issue of Proceedings of the Royal Society B: Biological Sciences. Revised submissio

Co-Variation between Seed Dormancy, Growth Rate and Flowering Time Changes with Latitude in Arabidopsis thaliana

Life-history traits controlling the duration and timing of developmental phases in the life cycle jointly determine fitness. Therefore, life-history traits studied in isolation provide an incomplete view on the relevance of life-cycle variation for adaptation. In this study, we examine genetic variation in traits covering the major life history events of the annual species Arabidopsis thaliana: seed dormancy, vegetative growth rate and flowering time. In a sample of 112 genotypes collected throughout the European range of the species, both seed dormancy and flowering time follow a latitudinal gradient independent of the major population structure gradient. This finding confirms previous studies reporting the adaptive evolution of these two traits. Here, however, we further analyze patterns of co-variation among traits. We observe that co-variation between primary dormancy, vegetative growth rate and flowering time also follows a latitudinal cline. At higher latitudes, vegetative growth rate is positively correlated with primary dormancy and negatively with flowering time. In the South, this trend disappears. Patterns of trait co-variation change, presumably because major environmental gradients shift with latitude. This pattern appears unrelated to population structure, suggesting that changes in the coordinated evolution of major life history traits is adaptive. Our data suggest that A. thaliana provides a good model for the evolution of trade-offs and their genetic basis.<br

Linked neutral diversity and divergence as a function of distance from fixed substitutions across the <i>C. grandiflora</i> genome.

<p>A) Diversity at 4-fold degenerate sites, B) Divergence at 4-fold degenerate sites, and C) Diversity/divergence at 4-fold degenerate sites. In all figures, black lines represent measures surrounding fixed replacement substitutions and gray shading represents 95% confidence intervals, from bootstrapping, surrounding silent substitutions.</p

Estimates of negative and positive selection on coding and noncoding sites in <i>C. grandiflora</i>.

<p>A) The proportion of sites found in each bin of purifying selection strength, separated by site type, B) The proportion of divergent sites fixed by positive selection, and C) the rate of adaptive substitution relative to neutral divergence. Error bars represent 95% bootstrap confidence intervals.</p

Linked neutral diversity/divergence surrounding conserved noncoding sequences (CNSs).

<p>A) Diversity/divergence at 4-fold degenerate sites as a function of distance from fixed substitutions in CNSs (black lines) and fixed substitutions in non-conserved intergenic sequence (gray shading, 95% confidence interval). B) Diversity/divergence at 4-fold degenerate sites as a function of distance from CNSs containing fixed substitutions (black line) and CNSs without any fixed substitutions (gray shading, 95% confidence interval).</p

A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia

Diamond Blackfan anemia (DBA) is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Mutations in the gene encoding ribosomal protein S19 (RPS19) have been identified in approximately 25% of DBA families. Most of these mutations disrupt either the translation or stability of the RPS19 protein and are predicted to cause DBA by haploinsufficiency. However, approximately 30% of RPS19 mutations are missense mutations that do not alter the stability of the RPS19 protein and are hypothesized to act by a dominant negative mechanism. To formally test this hypothesis, we generated a transgenic mouse model expressing an RPS19 mutation in which an arginine residue is replaced with a tryptophan residue at codon 62 (RPS19R62W). Constitutive expression of RPS19R62W in developing mice was lethal. Conditional expression of RPS19R62W resulted in growth retardation, a mild anemia with reduced numbers of erythroid progenitors, and significant inhibition of terminal erythroid maturation, similar to DBA. RNA profiling demonstrated more than 700 dysregulated genes belonging to the same pathways that are disrupted in RNA profiles of DBA patient cells. We conclude that RPS19R62W is a dominant negative DBA mutation