BIN-ALI-Alignment
Sequence alignment concepts
(What is an “alignment”?)
Abstract:
This unit discusses the nature of a biological sequence "alignment".
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Prerequisites:
This unit builds on material covered in the following prerequisite units:
Contents
Evaluation
Evaluation: NA
Contents
- Take care of things, and they will take care of you.
- Shunryu Suzuki
Introduction
Sequence alignment is a very large, and important topic.
One of the foundations of bioinformatics is the empirical observation that related sequences conserve structure, and often function. Much of what we know about a protein's physiological function is based on the conservation of that function as the species evolves. Indeed, conservation is a defining aspect of what can rightly be said to be a protein's "function" in the first place. Conservation - or its opposite: variation - is a consequence of selection under constraints: protein sequences change as a consequence of DNA mutations, this changes the protein's structure, this in turn changes functions and that has multiple effects on a species' reproductive fitness. Detrimental variants may be removed. Variation that is tolerated is largely neutral and therefore found only in positions that are neither structurally nor functionally critical. Conservation patterns can thus provide evidence for many different questions: structural conservation among proteins with similar 3D-structures, functional conservation among homologues with comparable roles, or amino acid propensities as predictors for protein engineering and design tasks.
We assess conservation by comparing sequences between related proteins. This is the basis on which we can make inferences from well-studied model organisms for species that have not been studied as deeply. The foundation is to measure protein sequence similarity. If two sequences are much more similar than we could expect from chance, we hypothesize that their similarity comes from shared ancestry plus conservation. The measurement of sequence similarity however requires sequence alignment[1].
A carefully done sequence alignment is a cornerstone for the annotation of the essential properties a gene or protein. It can already tell us a lot about which proteins we expect to have similar functions in different species.
Task:
- Read the introductory notes on what sequence alignments mean.
Self-evaluation
Further reading, links and resources
Notes
- ↑ This is not strictly true in all cases: some algorithms measure similarity through an alignment-free approach, for example by comparing structural features, or domain annotations. These methods are less sensitive, but important when sequences are so highly diverged that no meaningful sequence alignment can be produced.
About ...
Author:
- Boris Steipe <boris.steipe@utoronto.ca>
Created:
- 2017-08-05
Modified:
- 2017-10-20
Version:
- 1.0
Version history:
- 1.0 First live version
- 0.1 First stub
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