Evolution of vertebrates may inform disease prevention

Researchers at the University of St Andrews used long-molecule DNA sequencing in a sea squirt, a lamprey and a frog and found increased isoform diversity in certain signalling-output genes at the invertebrate–vertebrate transition, a result reported in BMC Biology.

New research from the University of St Andrews used long-molecule DNA sequencing in a sea squirt, a lamprey and a frog to examine genes that act at the outputs of major intercellular signalling pathways. These output proteins guide cell responses during embryo and organ development and are frequent targets in disease-causing mutations and pharmaceutical work. The team found that a small set of signalling-output genes produced a higher number of distinct protein isoforms in the lamprey and frog than in the sea squirt. The pattern of increased isoform diversity appears to have arisen at the invertebrate–vertebrate transition and is reported as likely relevant to the origin and diversification of vertebrates. Key findings: - Researchers generated new long-read sequencing data from a sea squirt, a lamprey and a frog. - Long-molecule sequencing allowed distinction of different transcripts from individual genes in these animals for the first time. - Signalling-output genes showed greater isoform diversity in the lamprey and frog compared with the invertebrate sea squirt. - The affected proteins sit at the ends of major signalling pathways and control final cellular responses during development. - The results are reported in the journal BMC Biology in a paper titled "Long read sequencing reveals increased isoform diversity in key transcription factor effectors of intercellular signalling at the invertebrate vertebrate transition." Summary: These findings identify a distinct change in how a small set of signalling-output genes produce protein variants at the origin of vertebrates, which helps explain aspects of increased developmental complexity. The authors note the work could be relevant for understanding how these pathways are involved in disease; how that connection might be explored is undetermined at this time.