A Comprehensive Analysis of Fibrillar Collagens in Lamprey Suggests a Conserved Role in Vertebrate Musculoskeletal Evolution

Abstract

Vertebrates have distinct tissues which are not present in invertebrate chordates nor other metazoans. The rise of these tissues also coincided with at least one round of whole-genome duplication as well as a suite of lineage-specific segmental duplications. Understanding whether novel genes lead to the origin and diversification of novel cell types, therefore, is of great importance in vertebrate evolution. Here we were particularly interested in the evolution of the vertebrate musculoskeletal system, the muscles and connective tissues that support a diversity of body plans. A major component of the musculoskeletal extracellular matrix (ECM) is fibrillar collagens, a gene family which has been greatly expanded upon in vertebrates. We thus asked whether the repertoire of fibrillar collagens in vertebrates reflects differences in the musculoskeletal system. To test this, we explored the diversity of fibrillar collagens in lamprey, a jawless vertebrate which diverged from jawed vertebrates (gnathostomes) more than five hundred million years ago and has undergone its own gene duplications. Some of the principal components of vertebrate hyaline cartilage are the fibrillar collagens type II and XI, but their presence in cartilage development across all vertebrate taxa has been disputed. We particularly emphasized the characterization of genes in the lamprey hyaline cartilage, testing if its collagen repertoire was similar to that in gnathostomes. Overall, we discovered thirteen fibrillar collagens from all known gene subfamilies in lamprey and were able to identify several lineage-specific duplications. We found that, while the collagen loci have undergone rearrangement, the Clade A genes have remained linked with the hox clusters, a phenomenon also seen in gnathostomes. While the lamprey muscular tissue was largely similar to that seen in gnathostomes, we saw considerable differences in the larval lamprey skeletal tissue, with distinct collagen combinations pertaining to different cartilage types. Our gene expression analyses were unable to identify type II collagen in the sea lamprey hyaline cartilage nor any other fibrillar collagen during chondrogenesis at the stages observed, meaning that sea lamprey likely no longer require these genes during early cartilage development. Our findings suggest that fibrillar collagens were multifunctional across the musculoskeletal system in the last common ancestor of vertebrates and have been largely conserved, but these genes alone cannot explain the origin of novel cell types.

Cranial cartilages: Players in the evolution of the cranium during evolution of the chordates in general and of the vertebrates in particular

“…Mucocartilage, which is now considered homogenous for fibrillar collagens (Root et al, 2022), consists of mucopolysaccharides and mesenchyme and is once considered a unique tissue for larval lampreys (Wright & Youson, 1982). A recent study systematically revealed the evolution of the collagen gene family in vertebrates and showed cyclostome-specific gain or loss of genes (Root et al, 2022). Hence, true cartilage in vertebrates can be considered as consisting of type II collagen fibers and chondrocytes.…”

“…The major differences between the skeletal systems of gnathostomes and cyclostomes are (1) absence of bone in cyclostomes and (2) evolution of new proteins in cyclostomes (lamprin, myxinin, and pharymprin) in addition to collagen fibers (Root et al, 2022). Lamprin is an elastin‐like fiber expressed in annular, trabecular, and piston cartilage but not in branchial and pericardial cartilages (Fernandes & Eyre, 1999; McBurney & Wright, 1996; Robson et al, 2000).…”

“…Lampreys also have characteristic cartilages called mucocartilage in the oral and pharyngeal regions that is derived from the mandibular and hyoid arches (Gaskell, 1908; Johnels, 1948). Mucocartilage, which is now considered homogenous for fibrillar collagens (Root et al, 2022), consists of mucopolysaccharides and mesenchyme and is once considered a unique tissue for larval lampreys (Wright & Youson, 1982). A recent study systematically revealed the evolution of the collagen gene family in vertebrates and showed cyclostome‐specific gain or loss of genes (Root et al, 2022).…”

“…Among the cranial elements, the developmental and evolutionary origins of the cranium has been a major topic in comparative morphology since the 19th century (Huxley, 1858). The cranium is composed of the neurocranium, which encloses the brain and sensory organs, and the viscerocranium, which includes the jaw and pharyngeal skeletons (Romer, 1977). One of the earliest studies on the cranial origin focused on the similarities and differences between the cranium and vertebrae (Goethe, 1790), with the vertebral theory regarding the cranium as a group of vertebrae (Goethe, 1790).…”