Function preserves sequences Christophe Roos - MediCel ltd [email protected] Similarity is the result of conservation or converging evolution

Function preserves sequences

Christophe RoosChristophe Roos - - MediCel ltdMediCel [email protected]

Similarity is the result of conservation or converging

evolution – it has its reason of being

Mutations change sequences

Spring 2002Christophe Roos - 3/6 Sequence databases & comparison

The public biological databases

• EMBL or GenBank or DDBJ for DNA– emblnew for daily updates, merges the main DB 4x/year

• SwissProt or PIR for proteins– Trembl, tremblnew, remtrembl

• PDB for structures

• In flat file format, yet quite informative and convertible– Fasta format is a ‘universal’ sequence format: first line starts with ‘>’

followed by free text. Second line has the start of the sequence (50 or 60 characters per line). Use the first line for the name or the Accession Number (AC)


Database homes

• The European database home is in Hinxton, Cambridge, UK: European Bioinformatics Institute - EBI – http://www.ebi.ac.uk– Access through the Sequence Retrieval System, SRS

• The American database home is in Washington DC: National Center for Biotechnology Information – NCBI– http://www.ncbi.nlm.nih.gov– Access through Entrez

• Both centers exchange their data on a daily basis, however there are differences in annotations, consistency, speed and quality.

• There is also a Japanese database provider, DDBJ.


A look at one entry from EMBL

part 1/3



part 2/3



part 3/3

The feature table of the entry contains several linkeditems, such as exon-assembly (mRNA) and codingsequence (CDS).There are also cross-references to other databases


A look at one entry from SwissProt

The eyeless gene: a master regulatory gene in eye formation


The effect of the eyeless gene

The eyeless gene is a master regulatory gene in eye formation• When it is absent, no eyes are formed• When it is present where it should not, it induces eye formation

Normal

Ove

rexp

ress

ed in

ant

enna

e an

d w

ings

Absent



Part 2: the annotations about the function and location



Part 3: The feature table and the amino acid sequence



The eyeless gene is also called PAX6 and can be foundin several species: birds, mammals, reptiles, fish, invertebrates


Sequence comparison

• Function by analogy: If sequences are conserved their function is probably also conserved.

• Functional domains: If some parts of the sequences are more conserved than other parts, there must be an underlying biological reason for it.

• Establishing relationship/differences in function: By quantification of sequence relationships it is possible to estimate function of novel genes

• Establishing relationship between species

- Why?


Sequence comparison – how?

• Compare two sequences of similar length• Compare two sequences of very different length• Compare several sequences• Allow gaps or not?• Scoring: yes-no or good-intermediate-bad• The best or all above a threshold?


Sequence comparison – metrics

• The scoring matrix • The score for a match• The penality for a mismatch• The penality for the insertion of a gap (gap-open)• The penality for elongating a gap (gap-length)• Local or global similarities ?

GA-CGGATTAG

GATCGGAATAG

mismatch

gapmatch

Documents

Function preserves sequences Christophe Roos - MediCel ltd [email protected] Similarity is the result of conservation or converging evolution