External length is one of the most conspicuous aspects of mammalian tail morphological diversity. Factors that influence the evolution of tail length diversity have been proposed for particular taxa, including habitat, diet, locomotion and climate. However, no study to date has investigated such factors at a large phylogenetic scale to elucidate what drives tail length evolution in and across mammalian lineages. We use phylogenetic comparative methods to test a priori hypotheses regarding proposed factors influencing tail length, explore possible interactions between factors using evolutionary best-fit models, and map evolutionary patterns of tail length for specific mammalian lineages. Across mammals, substrate use is a significant factor influencing tail length, with arboreal species maintaining selection for longer tails. Non-arboreal species instead exhibit a wider range of tail lengths, secondarily influenced by differences in locomotion, diet and climate. Tail loss events are revealed to occur in the context of both long and short tails and influential factors are clade dependent. Some mammalian groups (e.g. Macaca ; primates) exhibit elevated rates of tail length evolution, indicating that morphological evolution may be accelerated in groups characterized by diverse substrate use, locomotor modes and climate.

Background: Variation in facial shape may arise from the combinatorial or overlapping actions of paralogous genes. Given its many members, and overlapping expression and functions, the EPH receptor family is a compelling candidate source of craniofacial morphological variation. We performed a detailed morphometric analysis of an allelic series of E14.5 Ephb1-3 receptor mutants to determine the effect of each paralogous receptor gene on craniofacial morphology. Results: We found that Ephb1, Ephb2, and Ephb3 genotypes significantly influenced facial shape, but Ephb1 effects were weaker than Ephb2 and Ephb3 effects. Ephb2 À/À and Ephb3 À/À mutations affected similar aspects of facial morphology, but Ephb3 À/À mutants had additional facial shape effects. Craniofacial differences across the allelic series were largely consistent with predicted additive genetic effects. However, we identified a potentially important nonadditive effect where Ephb1 mutants displayed different morphologies depending on the combination of other Ephb paralogs present, where Ephb1 +/À , Ephb1 À/À , and Ephb1 À/À ; Ephb3 À/À mutants exhibited a consistent deviation from their predicted facial shapes. Conclusions: This study provides a detailed assessment of the effects of Ephb receptor gene paralogs on E14.5 mouse facial morphology and demonstrates how the loss of specific receptors contributes to facial dysmorphology.

There are two minor errors in figure 2 of the originally published manuscript. The scale colour bar accompanying the summary tree to signify slope value was flipped so that it was incorrectly labelled. In the corrected figure red represents slope of −4.4, and blue represents slope of 3.3. The labels for two branches in the summary tree representing significant shifts in slope and intercept for Caprinae and Bovinae were also switched. Correct slope and intercept values for all branches are included in the electronic supplementary material, and the errors described here have now been fixed in the figure submitted in this correction. These errors do not change the interpretation or accuracy of results.

EPHRIN‐B1 mutations underlie craniofrontonasal syndrome (CFNS), and signaling interactions between EPHRIN‐B1 ligand and the EPHB1, EPHB2, and EPHB3 receptors are presumed to be critical for normal craniofacial development. However, our understanding of the relative and spatial contribution of each receptor to facial morphogenesis remains incomplete. Here, we expand upon previous work by providing a detailed morphometric analysis of an E14.5 allelic seriesof Ephb1, Ephb2, and Ephb3 null mouse mutants. We assess the impact of individual receptor loss on facial morphology and compare observed facial shapes with those predicted by an additive genetic model. We found that Ephb1, Ephb2, and Ephb3 as well as facial size contribute significantly to facial shape. Predicted Principal Components (PC) scores of facial shape variation suggest a minimal global effect of Ephb1, with moderate effects of Ephb2 and Ephb3 on facial morphology. Observed scores for Ephb2 and Ephb3 homozygous single nulls align closely with predicted additive genetic scores, intermediate between controls and triple homozygous nulls. Compared to controls, triple homozygous nulls have wider orbits, inferiorly displaced nasals, and rostrally placed ear pinnae, suggesting an overall wider but shorter face. Ephb2 and Ephb3 mutants exhibit different facial shape effects, with Ephb2 homozygous nulls having infero‐laterally oriented orbits and less severe shape changes in the rest of the face. Predicted and observed PC scores for Ephb1/Ephb2 double nulls are similar to Ephb2 single nulls, and Ephb2/Ephb3 double nulls are similar to triple homozygous nulls. While facial shape variation across our sample is primarily explained by additive genetic effects, there is also a non‐additive Ephb1 effect that may be influencing facial shape and size. Predicted additive genetic PC scores place Ephb1 homozygous nulls close to controls, and Ephb1/Ephb3 homozygous double nulls close to Ephb3 homozygous nulls. These genotypes instead deviate from additive genetic predictions by having a relatively wider and shorter face, and overall smaller facial size. In sum, we have identified major additive genetic effects of Ephb1, Ephb2, and Ephb3 on facial shape development, as well as a more subtle non‐additive effect of Ephb1. We also describe specific morphologies associated with individual or compound loss of EPHB receptors and find overlapping and distinct facial shape effects of each. More broadly, this work helps identify signaling interactions that may occur between EPHRIN‐B1 and EPHB1, EPHB2, and EPHB3 receptorsand the role each plays during normal craniofacial development and CFNS.