Of Necks, Trunks and Tails: Axial Skeletal Diversity among Vertebrates

The axial skeleton of all vertebrates is composed of individual units known as vertebrae. Each vertebra has individual anatomical attributes, yet they can be classified in five different groups, namely cervical, thoracic, lumbar, sacral and caudal, according to shared characteristics and their association with specific body areas. Variations in vertebral number, size, morphological features and their distribution amongst the different regions of the vertebral column are a major source of the anatomical diversity observed among vertebrates. In this review I will discuss the impact of those variations on the anatomy of different vertebrate species and provide insights into the genetic origin of some remarkable morphological traits that often serve to classify phylogenetic branches or individual species, like the long trunks of snakes or the long necks of giraffes.

Discovery of benthol A and its challenging stereochemical assignment: opening up a new window for skeletal diversity of super-carbon-chain compounds

Super-carbon-chain compounds (SCCCs) are marine organic molecules featuring long polyol carbon chains with numerous stereocenters. Polyol-polyene compounds (PPCs) and ladder-frame polyethers (LFPs) are two major families. It is highly challenging...

Divergent synthesis of complex diterpenes through a hybrid oxidative approach

Polycyclic diterpenes exhibit many important biological activities, but de novo synthetic access to these molecules is highly challenging because of their structural complexity. Semisynthetic access has also been limited by the lack of chemical tools for scaffold modifications. We report a chemoenzymatic platform to access highly oxidized diterpenes by a hybrid oxidative approach that strategically combines chemical and enzymatic oxidation methods. This approach allows for selective oxidations of previously inaccessible sites on the parent carbocycles and enables abiotic skeletal rearrangements to additional underlying architectures. We synthesized a total of nine complex natural products with rich oxygenation patterns and skeletal diversity in 10 steps or less from ent-steviol.

Skeletal diversity in Pt- and Au-catalyzed annulations of allenedienes: dissecting unconventional mechanistic pathways

Unprecedented Pt- and Au-catalyzed divergent annulations of allenedienes are uncovered, together with mechanistic studies that reveal unanticipated pathways wherein homo-hyperconjugative interactions play a key role.

Palladium-catalysed cyclisation of vinylethylene carbonates and anhydrides: a new approach to diverse medium-sized bislactones

An unprecedented palladium-catalysed regioselective [5 + n] cyclisation (n = 5, 6, and 7) of vinylethylene carbonates and various anhydrides was presented. This protocol could offer a broad spectrum of medium-sized bislactones with skeletal diversity.

Facial shape and allometry quantitative trait locus intervals in the Diversity Outbred mouse are enriched for known skeletal and facial development genes

The biology of how faces are built and come to differ from one another is complex. Discovering the genes that contribute to differences in facial morphology is one key to untangling this complexity, with important implications for medicine and evolutionary biology. This study maps quantitative trait loci (QTL) for skeletal facial shape using Diversity Outbred (DO) mice. The DO is a randomly outcrossed population with high heterozygosity that captures the allelic diversity of eight inbred mouse lines from three subspecies. The study uses a sample of 1147 DO animals (the largest sample yet employed for a shape QTL study in mouse), each characterized by 22 three-dimensional landmarks, 56,885 autosomal and X-chromosome markers, and sex and age classifiers. We identified 37 facial shape QTL across 20 shape principal components (PCs) using a mixed effects regression that accounts for kinship among observations. The QTL include some previously identified intervals as well as new regions that expand the list of potential targets for future experimental study. Three QTL characterized shape associations with size (allometry). Median support interval size was 3.5 Mb. Narrowing additional analysis to QTL for the five largest magnitude shape PCs, we found significant overrepresentation of genes with known roles in growth, skeletal development, and sensory organ development. For most intervals, one or more of these genes lies within 0.25 Mb of the QTL’s peak. QTL effect sizes were small, with none explaining more than 0.5% of facial shape variation. Thus, our results are consistent with a model of facial diversity that is influenced by key genes in skeletal and facial development and, simultaneously, is highly polygenic.Author SummaryThe mammalian face is a complex structure serving many functions. We studied the genetic basis for facial skeletal diversity in a large sample of mice from an experimental population designed for the study of complex traits. We quantified the contribution of genetic variation to variation in three-dimensional facial shape across more than 55,000 genetic markers spread throughout the mouse genome. We found 37 genetic regions which are very likely to contribute to differences in facial shape. We then conducted a more detailed analysis of the genetic regions associated with the most variable aspects of facial shape. For these regions, a disproportionately large number of genes are known to be important to growth and to skeletal and facial development. The magnitude of these genetic contributions to differences in facial shape are consistently small. Our results therefore support the notion that facial skeletal diversity is influenced by many genes of small effect, but that some of these small effects may be related to genes that are fundamental to skeletal and facial development.