Abstract:
Background: Relaxin-3 (RLN3) is a highly conserved protein hormone found in species such as
flies, fish, rodents, and humans. Initially discovered as a neuropeptide, it modulates arousal, stress
response, feeding, metabolism, and memory. It also mediates peripheral actions during pregnancy
and has been found to relax the pelvic ligaments in guinea pigs. Due to its crucial role in human
neuronal process modulation, dysregulation of Relaxin-3 is often associated with mental illnesses,
leading to the emergence of Relaxin-3-based drugs as potential therapeutic agents.
Objectives: To re-examine the evolutionary relationship between vertebrates of different genera
to decipher a conserved domain evolutionary relationship with the reference species Homo
sapiens, using several bioinformatics tools
Methods: This study commenced with a comprehensive literature review, followed by selecting
28 vertebrate species known to possess the Relaxin-3 protein. The amino acid sequences were
retrieved using FASTA and subsequently analysed through BLAST for sequence comparison.
Multiple sequence alignment was conducted using Clustal Omega, followed by constructing a
phylogenetic tree and a conserved domain search to elucidate evolutionary relationships and
functional characteristics.
Results: Phylogenetic tree suggested the close relation of Homo sapiens and Piliocolobus
tephrosceles (primate), Conserved domain sequences confirmed the evolutionary relationship of
Relaxin-3 protein in Piliocolobus tephrosceles to Homo sapiens with 92.957% similarity followed
by Pogona vitticeps (reptile) with 22.535%. Zonotrichia albicolis (Aves) shows more similarity to
Homo sapiens, than Rhincodon typus (Orectolobiformes) and Maylandia zebra (Pisces:
perciformes) with 20.512% in conserved domain sequence analysis. These findings indicate that
Relaxin-3 protein is highly conserved across species, and the protein's evolutionary divergence
reflects the varying degrees of neural complexity among vertebrates.
Conclusions: Cladistics confirmed Relaxin-3’s monophyletic conservation in primates (92.96%
similarity), with divergent but functional retention in reptiles (22.54%) and birds (20.51%).
Phylogeny mirrors vertebrate neural complexity, though deeper divergences require further
resolution.
