Covariation of brain and skull shapes as a model to understand the role of crosstalk in development and evolution.

Covariation among discrete phenotypes can arise due to selection for shared functions, and/or shared genetic and developmental underpinnings. The consequences of such phenotypic integration are far-reaching and can act to either facilitate or limit morphological variation. The vertebrate brain is known to act as an "organizer" of craniofacial development, secreting morphogens that can affect the shape of the growing neurocranium, consistent with roles for pleiotropy in brain-neurocranium covariation. Here, we test this hypothesis in cichlid fishes by first examining the degree of shape integration between the brain and the neurocranium using three-dimensional geometric morphometrics in an F5 hybrid population, and then genetically mapping trait covariation using quantitative trait loci (QTL) analysis. We observe shape associations between the brain and the neurocranium, a pattern that holds even when we assess associations between the brain and constituent parts of the neurocranium: the rostrum and braincase. We also recover robust genetic signals for both hard- and soft-tissue traits and identify a genomic region where QTL for the brain and braincase overlap, implicating a role for pleiotropy in patterning trait covariation. Fine mapping of the overlapping genomic region identifies a candidate gene, notch1a, which is known to be involved in patterning skeletal and neural tissues during development. Taken together, these data offer a genetic hypothesis for brain-neurocranium covariation, as well as a potential mechanism by which behavioral shifts may simultaneously drive rapid change in neuroanatomy and craniofacial morphology.

Weak genetic signal for phenotypic integration implicates developmental processes as major regulators of trait covariation.

Phenotypic integration is an important metric that describes the degree of covariation among traits in a population, and is hypothesized to arise due to selection for shared functional processes. Our ability to identify the genetic and/or developmental underpinnings of integration is marred by temporally overlapping cell-, tissue- and structure-level processes that serve to continually 'overwrite' the structure of covariation among traits through ontogeny. Here, we examine whether traits that are integrated at the phenotypic level also exhibit a shared genetic basis (e.g. pleiotropy). We micro-CT scanned two hard tissue traits, and two soft tissue traits (mandible, pectoral girdle, atrium and ventricle, respectively) from an F5 hybrid population of Lake Malawi cichlids, and used geometric morphometrics to extract 3D shape information from each trait. Given the large degree of asymmetric variation that may reflect developmental instability, we separated symmetric from asymmetric components of shape variation. We then performed quantitative trait loci (QTL) analysis to determine the degree of genetic overlap between shapes. While we found ubiquitous associations among traits at the phenotypic level, except for a handful of notable exceptions, our QTL analysis revealed few overlapping genetic regions. Taken together, this indicates developmental interactions can play a large role in determining the degree of phenotypic integration among traits, and likely obfuscate the genotype to phenotype map, limiting our ability to gain a comprehensive picture of the genetic contributors responsible for phenotypic divergence.