Global constraints within the developmental program of the Drosophila wing.

Vasyl Alba,Richard W Carthew,Madhav Mani,James E Carthew

doi:10.7554/elife.66750

Abstract

Organismal development is a complex process, involving a vast number of molecular constituents interacting on multiple spatio-temporal scales in the formation of intricate body structures. Despite this complexity, development is remarkably reproducible and displays tolerance to both genetic and environmental perturbations. This robustness implies the existence of hidden simplicities in developmental programs. Here, using the Drosophila wing as a model system, we develop a new quantitative strategy that enables a robust description of biologically salient phenotypic variation. Analyzing natural phenotypic variation across a highly outbred population and variation generated by weak perturbations in genetic and environmental conditions, we observe a highly constrained set of wing phenotypes. Remarkably, the phenotypic variants can be described by a single integrated mode that corresponds to a non-intuitive combination of structural variations across the wing. This work demonstrates the presence of constraints that funnel environmental inputs and genetic variation into phenotypes stretched along a single axis in morphological space. Our results provide quantitative insights into the nature of robustness in complex forms while yet accommodating the potential for evolutionary variations. Methodologically, we introduce a general strategy for finding such invariances in other developmental contexts.

Highlights

One of the most salient features of organismal development is its reproducibility and tolerance to environmentalIt has been noted that there is an apparent paradox related to robustness [2,3,4,5,6]
Using the Drosophila wing as a model system, we develop a new quantitative strategy that enables a robust description of biologically salient phenotypic variation
Analyzing natural phenotypic variation across a highly outbred population, and variation generated by weak perturbations in genetic and environmental conditions, we observe a highly constrained set of wing phenotypes

Summary

Introduction

It has been noted that there is an apparent paradox related to robustness [2,3,4,5,6]. We find that the outcomes of wing development can be statistically described by a one-dimensional linear manifold in morphological space that corresponds to a non-intuitive combination of structural variations across the wing This dominant mode is systematically excited by variants generated by very weak mutations in signaling pathway genes as well as by thermal and dietary environmental perturbations. Our work provides direct empirical evidence for the presence of global constraints within the developmental program of the wing, funneling environmental inputs and genetic variation into phenotypes stretched along a single axis in morphological space. While the developmental outcomes are globally constrained, there exists the potential for morphological variation along the unconstrained direction This provides a dissolution of the apparent conflict between robustness and evolvability. This general strategy used to study the wing formulates an approach for finding such constraints in a broader class of developmental processes

Results

A Dominant Mode of Natural Phenotypic Variation

Methods