Dynamic Programming

How to match up sequences and have the matches make sense

and be quantitative

Question is

• How does a specific sequence compare to one other specific sequence?– Is it similar?– If so, at what level?

• Can’t compare every base to every other base--to complex

You are in the driver’s seat

• What is the most important?– Exact nucleotide match?– One-for-one (no gaps)?– Length

Mathematical model

• Derive equation for each position, based on your value system

• Methodically go through each base for each sequence and calculate the value

• At the end, find the optimal path

Starting point: three possible scenarios for each position in

sequences X and Y• At a given position, the bases (Xm and Yn)

are identical in X and Y• At a given position, the base (Xm) in X is

aligned with a gap in Y (and Yn appeared earlier)

• At a given position, the base in Y is aligned with a gap in X (and Xm appeared earlier)

Assign a value to each situation

• Identical: +5• Mismatch: -2• Insertion or deletion: -6

(Could have others; could choose different values)

http://www.acm.org/crossroads/xrds13-1/dna.html

Alpha-glucosidase in plants:

Enzymes sharing WIDMNE signature sequence

alpha-glucosidase (all groups)alpha-xylosidase (plant, bacteria, archaea)Sucrase/Isomaltase (animal)

Related sequences with broad substrate specificity

0.1

Tp GAA

Bh BAB0442

Bt Aglu-III

Ss xylS

Lp XylQTm

AAD3539

Aa GlcA

Sc CAB8890

Ce AAA8317

Lv GAA

Hs S/I-C

Hs S/I-N

Cj GAAI

Cj GAAII

Hs GAA

Hv Aglu

At Aglu-1

Bv AgluSo Aglu

Pp BAB3946

St MAL2

AtXYL1

TmXYL

MjAglu Pt Aglu

Sp Aglu

Anig aglA

An AgdA

Ca GAM1

Soc GAM1

An agdB

Fungi

Protista

Bacteria

Plantae

Animalia

Archaea

Plant -amylases are located in different cellular compartments

Plastids (chloroplasts, amyloplasts)CytosolApoplast (cell wall space)

What is the function of the non-plastid forms?

dodder

adzuki bean

morning glory

rice 2Abarley A

barley B

rice 3B

maize

rice 3E

rice XP_472377

cassava

apple 9

apple 8

potato plantain

rice NP_916641

kiwifruit

apple 10

Clade ISecreted

421-445 aa

Clade IICytosolic

407-414 aaClade IIIPlastidic

877-906 aa

Arabidopsis AMY1

Arabidopsis AMY2

Arabidopsis AMY3

Homologous sequences (homologues)Share a common ancestor

ParalogsHomologues derived by gene duplicationFunctions may varyLook for differences

OrthologsHomologues derived by speciationCommon functionLook for similarities

Use alignments to look for:

• Structures important for common functions (orthologs)

• Structures important for unique functions (paralogs)

• Unusual structures

N C

AtAMY1

AMY1 has a three amino acid deletion

3

Red: NHDTGST Blue: VAEIW

Barley -amylase

Active site residues

Variation in the active site loop among plant and bacterial -amylases

AtAMY1