Mouse Skull Mean Shape and Shape Robustness Rely on Different Genetic Architectures and Different Loci

The genetic architecture of skull shape has been extensively studied in mice and the results suggest a highly polygenic and additive basis. In contrast few studies have explored the genetic basis of the skull variability. Canalization and developmental stability are the two components of phenotypic robustness. They have been proposed to be emergent properties of the genetic networks underlying the development of the trait itself, but this hypothesis has been rarely tested empirically. Here we use outbred mice to investigate the genetic architecture of canalization of the skull shape by implementing a genome-wide marginal epistatic test on 3D geometric morphometric data. The same data set had been used previously to explore the genetic architecture of the skull mean shape and its developmental stability. Here, we address two questions: (1) Are changes in mean shape and changes in shape variance associated with the same genomic regions? and (2) Do canalization and developmental stability rely on the same loci and genetic architecture and do they involve the same patterns of shape variation? We found that unlike skull mean shape, among-individual shape variance and fluctuating asymmetry (FA) show a total lack of additive effects. They are both associated with complex networks of epistatic interactions involving many genes (protein-coding and regulatory elements). Remarkably, none of the genomic loci affecting mean shape contribute these networks despite their enrichment for genes involved in craniofacial variation and diseases. We also found that the patterns of shape FA and individual variation are largely similar and rely on similar multilocus epistatic genetic networks, suggesting that the processes channeling variation within and among individuals are largely common. However, the loci involved in these two networks are completely different. This in turn underlines the difference in the origin of the variation at these two levels, and points at buffering processes that may be specific to each level

Limited thermal plasticity and geographical divergence in the ovipositor of Drosophila suzukii

Phenotypic plasticity has been repeatedly suggested to facilitate adaptation to new environmental conditions, as in invasions. Here, we investigate this possibility by focusing on the worldwide invasion of Drosophila suzukii: an invasive species that has rapidly colonized all continents over the last decade. This species is characterized by a highly developed ovipositor, allowing females to lay eggs through the skin of ripe fruits. Using a novel approach based on the combined use of scanning electron microscopy and photogrammetry, we quantified the ovipositor size and three-dimensional shape, contrasting invasive and native populations raised at three different developmental temperatures. We found a small but significant effect of temperature and geographical origin on the ovipositor shape, showing the occurrence of both geographical differentiation and plasticity to temperature. The shape reaction norms are in turn strikingly similar among populations, suggesting very little difference in shape plasticity among invasive and native populations, and therefore rejecting the hypothesis of a particular role for the plasticity of the ovipositor in the invasion success. Overall, the ovipositor shape seems to be a fairly robust trait, indicative of stabilizing selection. The large performance spectrum rather than the flexibility of the ovipositor would thus contribute to the success of D. suzukii worldwide invasion.Peer reviewe

A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice

Disentangling directional and fluctuating asymmetry in a genome-wide association study.

8 pagesInternational audienceAlthough directional and fluctuating asymmetry have been frequently assessed independently, they are indeed associated concepts both in theory and in practice. However, they can be difficult to disentangle in genome-wide association studies, where the appropriate shape statistics are not fully developed. Although the usage of Procrustes distances to overcome this problem may be tempting, this does not reliably help to identify the underlying genetic components of directional and fluctuating asymmetries. Here, similarities and differences among different approaches have revealed that the genetic component of the skull asymmetry in this population of mice is mostly associated to fluctuating asymmetry. This is coherent with the previous literature and it adds a note of caution in the study of asymmetry in a genomic context. The results also pointed out at the need of developing a multivariate framework to conduct shape analyses in general and asymmetry tests specifically. The combination of high-dimensional shape data and the vast number of genomic markers makes it challenging but the different statistical errors can hide important biological information

Estimating Phylogenies from Shape and Similar Multidimensional Data: Why It Is Not Reliable

In recent years, there has been controversy whether multidimensional data such as geometric morphometric data or information on gene expression can be used for estimating phylogenies. This study uses simulations of evolution in multidimensional phenotype spaces to address this question and to identify specific factors that are important for answering it. Most of the simulations use phylogenies with four taxa, so that there are just three possible unrooted trees and the effect of different combinations of branch lengths can be studied systematically. In a comparison of methods, squared-change parsimony performed similarly well as maximum likelihood, and both methods outperformed Wagner and Euclidean parsimony, neighbor-joining and UPGMA. Under an evolutionary model of isotropic Brownian motion, phylogeny can be estimated reliably if dimensionality is high, even with relatively unfavorable combinations of branch lengths. By contrast, if there is phenotypic integration such that most variation is concentrated in one or a few dimensions, the reliability of phylogenetic estimates is severely reduced. Evolutionary models with stabilizing selection also produce highly unreliable estimates, which are little better than picking a phylogenetic tree at random. To examine how these results apply to phylogenies with more than four taxa, we conducted further simulations with up to eight taxa, which indicated that the effects of dimensionality and phenotypic integration extend to more than four taxa, and that convergence among internal nodes may produce additional complications specifically for greater numbers of taxa. Overall, the simulations suggest that multidimensional data, under evolutionary models that are plausible for biological data, do not produce reliable estimates of phylogeny.Zip file with Supplementary materialX Online Appendix 1 - Mahalanobis distances.pdf Brief description of the methods and results for the simulations run using Mahalanobis distances. X Online Appendix 2 - Tree topologies Brief description of the methods and results for the simulations using more than four taxa and different topologies. X R Scripts R Scripts used in this paper. Within that folder you can find another README file with a brief description of each script. X Supplementary Figure S1.pdf Results from the simulations exploring the effect of number of taxa on tree distances by using quartet distances. X Tables S1, S2 and S3 Results for the comparison among phylogenetic methods.Online material.zipThe paper contains simulations, for which R scripts are avaiable here

Mouse Skull Mean Shape and Shape Robustness Rely on Different Genetic Architectures and Different Loci

International audienceThe genetic architecture of skull shape has been extensively studied in mice and the results suggest a highly polygenic and additive basis. In contrast few studies have explored the genetic basis of the skull variability. Canalization and developmental stability are the two components of phenotypic robustness. They have been proposed to be emergent properties of the genetic networks underlying the development of the trait itself, but this hypothesis has been rarely tested empirically. Here we use outbred mice to investigate the genetic architecture of canalization of the skull shape by implementing a genome-wide marginal epistatic test on 3D geometric morphometric data. The same data set had been used previously to explore the genetic architecture of the skull mean shape and its developmental stability. Here, we address two questions: (1) Are changes in mean shape and changes in shape variance associated with the same genomic regions? and (2) Do canalization and developmental stability rely on the same loci and genetic architecture and do they involve the same patterns of shape variation? We found that unlike skull mean shape, among-individual shape variance and fluctuating asymmetry (FA) show a total lack of additive effects. They are both associated with complex networks of epistatic interactions involving many genes (protein-coding and regulatory elements). Remarkably, none of the genomic loci affecting mean shape contribute these networks despite their enrichment for genes involved in craniofacial variation and diseases. We also found that the patterns of shape FA and individual variation are largely similar and rely on similar multilocus epistatic genetic networks, suggesting that the processes channeling variation within and among individuals are largely common. However, the loci involved in these two networks are completely different. This in turn underlines the difference in the origin of the variation at these two levels, and points at buffering processes that may be specific to each level

Epistasis regulates the developmental stability of the mouse craniofacial shape.

12 pagesInternational audienceFluctuating asymmetry is a classic concept linked to organismal development. It has traditionally been used as a measure ofdevelopmental instability, which is the inability of an organism to buffer environmental fluctuations during development.Developmental stability has a genetic component that influences the final phenotype of the organism and can lead tocongenital disorders. According to alternative hypotheses, this genetic component might be either the result of additivegenetic effects or a by-product of developmental gene networks. Here we present a genome-wide association study of thegenetic architecture of fluctuating asymmetry of the skull shape in mice. Geometric morphometric methods were applied toquantify fluctuating asymmetry: we estimated fluctuating asymmetry as Mahalanobis distances to the mean asymmetry,correcting first for genetic directional asymmetry. We applied the marginal epistasis test to study epistasis among genomicregions. Results showed no evidence of additive effects but several interacting regions significantly associated withfluctuating asymmetry. Among the candidate genes overlapping these interacting regions we found an over-representation ofgenes involved in craniofacial development. A gene network is likely to be associated with skull developmental stability, andgenes originally described as buffering genes (e.g., Hspa2) might occupy central positions within these networks, whereregulatory elements may also play an important role. Our results constitute an important step in the exploration of themolecular roots of developmental stability and the first empirical evidence about its genetic architecture