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All Sequence Alignment questions

Question 8 of 20 Fundamentals Concept

What is the difference between orthologs and paralogs?

Short answer

Both are homologs, genes that share a common ancestor. Orthologs separated through a speciation event, so they are the corresponding gene in two species. Paralogs separated through a gene duplication, so they can sit in the same genome and are freer to evolve new functions.

Why

Homology is about shared ancestry, and the two terms describe how that ancestry split. Pearson's introduction to homology searching, following Koonin, defines orthologs as homologous sequences that differ because of speciation and paralogs as homologs produced by gene duplication. Orthologs tend to follow the species tree and are the usual basis for transferring a function from a model organism to humans.

After a duplication, one copy can keep the original role while the other is free to change, so paralogs are more likely to acquire new functions. Pearson gives trypsin and chymotrypsin as paralogous serine proteases that cut at different residues. The distinction matters in practice.

If you pick the mouse gene most similar to a human gene, you usually get the ortholog, but not always. Unequal rates of evolution after a duplication can make a paralog look closer. The labels also depend on the tree: genes duplicated after two species split are both orthologous to the single gene in the other species, which is why one-to-many orthology exists.

A strong answer covers

  • Homologs share ancestry, orthologs and paralogs describe the split
  • Orthologs arise by speciation
  • Paralogs arise by duplication and often diverge in function
  • Function transfer usually relies on orthologs
  • One-to-many orthology follows lineage-specific duplication

Common mistakes

  • Using ortholog to mean any similar gene in another species
  • Assuming the most similar sequence is always the ortholog
  • Treating paralogs as having the same function by default