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Distant Homology BLASTP Searches.

Donard S Dwyer1

  • 1Departments of Psychiatry and Behavioral Medicine and Pharmacology, Toxicology and Neuroscience, LSU Health Shreveport, Shreveport, LA, USA. donard.dwyer@lsuhs.edu.

Methods in Molecular Biology (Clifton, N.J.)
|November 1, 2025
PubMed
Summary

Relaxed BLASTP searches identified functional neuropeptide counterparts in C. elegans. This method reveals evolutionary links between conserved peptides like kisspeptin and amylin (islet amyloid polypeptide) and their ancient ancestors.

Keywords:
Basic local alignment search tool (BLAST)Evolutionary conservationNeuropeptidesRFamideSequence homology

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Area of Science:

  • Evolutionary biology
  • Comparative genomics
  • Neuropeptide research

Background:

  • Neuropeptides are conserved across species, offering insights into common functions.
  • Standard BLASTP often misses homologous neuropeptides in distantly related species like C. elegans.

Purpose of the Study:

  • To identify functional counterparts of kisspeptin and amylin (islet amyloid polypeptide - IAPP) in C. elegans.
  • To demonstrate the utility of relaxed BLASTP settings for distant homology detection.

Main Methods:

  • Utilized BLASTP with relaxed parameters (e.g., increased E-value) to broaden homology searches.
  • Validated potential homologs by cross-referencing with neuropeptides from other species.
  • Analyzed sequence convergence to confirm candidate functional counterparts.

Main Results:

  • Identified strong candidates for functional counterparts of kisspeptin and IAPP in C. elegans.
  • Discovered a hybrid neuropeptide (FLP-12) suggesting ancestral gene duplication and divergence.
  • Demonstrated that relaxed BLASTP is effective for finding evolutionarily distant neuropeptide relatives.

Conclusions:

  • Relaxed BLASTP is a powerful tool for identifying distant neuropeptide homologs.
  • This approach aids in characterizing evolutionary relationships and ancient common ancestors of neuropeptides.
  • Findings contribute to understanding neuropeptide evolution and conserved biological functions.