--- title: "Annotation, orthologues and comparative genomics" description: "Genome annotation locates features and proposes functions using sequence evidence and other data. Orthologues diverge through speciation; paralogues diverge through duplication. Conservation can suppo" canonical: https://lightmysky.com/learn/science/annotation-orthologues-and-comparative-genomics-mt_eBRge2bLeC source: https://lightmysky.com/learn/science/annotation-orthologues-and-comparative-genomics-mt_eBRge2bLeC.md retrieved: 2026-11-12 --- > **Agent view.** This is the Markdown twin of the page, for tools and assistants. > When to use this site, and the call that answers each job: https://lightmysky.com/agent-instructions.md > API description (OpenAPI 3.1): https://lightmysky.com/openapi.json · Authentication: https://lightmysky.com/auth.md > Pricing: https://lightmysky.com/pricing.md · Catalog: https://lightmysky.com/llms.txt · Full catalog: https://lightmysky.com/llms-full.txt > Every machine-readable file on this domain: https://lightmysky.com/.well-known/ai-catalog.json > Ask for Markdown with `Accept: text/markdown`, a `.md` address, or `?mode=agent`. # Annotation, orthologues and comparative genomics Genome annotation locates features and proposes functions using sequence evidence and other data. Orthologues diverge through speciation; paralogues diverge through duplication. Conservation can support a functional hypothesis, but similarity and ancestry do not establish an exact function. Subject: Science · Area: Genetics & Evolution · Ages 21 to 22 Page: https://lightmysky.com/learn/science/annotation-orthologues-and-comparative-genomics-mt_eBRge2bLeC ## Ready when they can - Distinguishes genes related by speciation from genes related by duplication, and says why the difference matters for function. - Uses conservation across distant species as evidence of function, and states the limits of that argument. - Explains why an annotation transferred by similarity is a hypothesis rather than a result. ## Lesson: Gene relationships and functional hypotheses An assembly is useful before every gene is annotated. Annotation identifies features and attaches biological information. A match to a studied gene can suggest a function. Similarity alone does not confirm that function. Record transferred functions as predictions and test the proposed activity in its biological context. *(drawing: A sequence match suggests what to test. Measuring the proposed activity supplies different evidence.)* Orthologues are homologous genes whose ancestral copies separated through speciation. Paralogues separated through gene duplication. Paralogues can occur in different species when duplication preceded speciation. The ancestral event defines the relationship, not present location. Comparing gene and species trees helps infer these events; uncertain trees can leave the relationship unresolved. Orthology can guide function prediction without guaranteeing the same function. Duplicated copies may retain, divide or change ancestral activities. Orthologues can also differ in activity, expression or regulation. Use ancestry together with experimental evidence and biological context before transferring detailed claims. Less sequence change than a suitable neutral model predicts can suggest purifying selection: harmful changes tend to be removed. This supports functional constraint without identifying an exact function. A low mutation rate can also preserve sequence, so unchanged DNA alone is not proof. Conserved non-coding DNA may regulate expression or have another function. Conservation alone identifies neither a regulatory role nor its target gene. Test a regulatory proposal by changing the region and measuring expression against comparison samples. A structural role is also a function. **Recap.** Speciation defines orthology; duplication defines paralogy. Conservation and similarity support hypotheses, not automatic functional conclusions. *Lesson, questions and flashcards written for this dataset.* ## Practice 8 questions on this page, each with its working shown. ## Needs first - [Sequence alignment and reading a search result](https://lightmysky.com/learn/science/sequence-alignment-and-reading-a-search-result-mt_jNbEMFqgZ5) ## Opens up - [Association Studies and What They Can and Cannot Show](https://lightmysky.com/learn/science/association-studies-and-what-they-can-and-cannot-show-mt_IFFUFX3xrv) - [From a gene list to biology: enrichment tests and their backgrounds](https://lightmysky.com/learn/science/from-a-gene-list-to-biology-enrichment-tests-and-their-backgrounds-mt_M9eHEXq6iA)