Development and Evolution of the Muscles of the Pelvic Fin

Locomotor strategies in terrestrial tetrapods have evolved from the utilisation of sinusoidal contractions of axial musculature, evident in ancestral fish species, to the reliance on powerful and complex limb muscles to provide propulsive force. Within tetrapods, a hindlimb-dominant locomotor strategy predominates, and its evolution is considered critical for the evident success of the tetrapod transition onto land. Here, we determine the developmental mechanisms of pelvic fin muscle formation in living fish species at critical points within the vertebrate phylogeny and reveal a stepwise modification from a primitive to a more derived mode of pelvic fin muscle formation. A distinct process generates pelvic fin muscle in bony fishes that incorporates both primitive and derived characteristics of vertebrate appendicular muscle formation. We propose that the adoption of the fully derived mode of hindlimb muscle formation from this bimodal character state is an evolutionary innovation that was critical to the success of the tetrapod transition

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Emergence in evolution and the causal role of synergy

If reductionism and a search for deterministic, predictive 'laws' of nature represented the dominant research strategy – and world view – of the scientific community during the 20th century, 'emergence' has become a major theme, if not the dominant approach in the 21st century, reflecting a major shift of focus toward the study of complexity and complex systems. However, this important 'climate change' in the scientific enterprise has been accompanied by much confusion and debate about what exactly emergence is. How do you know it when you see it? Or don't see it? What are its defining properties? Is it possible to predict emergence? And is there more to emergence than meets the eye? Beyond these meta-theoretical issues, there is a deep question that is often skirted, or even ignored. How do we explain emergence? Why does emergence emerge? Here, I will briefly recount the history of this important concept and will address some of the many questions that surround it. I will also consider the distinction between reductionist and holistic approaches to the subject, as well as the distinction between epistemological and ontological emergence (that is, the ability to deduce or predict emergence versus the concrete reality of an emergent phenomenon). I will argue that living systems are irreducibly emergent in both senses and that biological evolution has quintessentially been a creative emergent process that is fully consistent with modern (Darwinian) evolutionary theory. Furthermore, as I will explain, novel 'synergies' of various kinds have been responsible for the 'progressive' evolution of more complex living systems over time. e selective advantages associated with emergent, synergistic effects have played a major causal role in the evolutionary process