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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.

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Dynamic programming

Dynamic Programming

How to match up sequences and have the matches make sense and be quantitative


Question is
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
You are in the driver’s seat

  • What is the most important?

    • Exact nucleotide match?

    • One-for-one (no gaps)?

    • Length


Mathematical model
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
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
Assign a value to each situation in sequences X and Y

  • Identical: +5

  • Mismatch: -2

  • Insertion or deletion: -6

    (Could have others; could choose different values)



  • Alpha-glucosidase in plants: in sequences X and Y

  • Enzymes sharing WIDMNE signature

  • sequence

    • alpha-glucosidase (all groups)

    • alpha-xylosidase (plant, bacteria, archaea)

    • Sucrase/Isomaltase (animal)

  • Related sequences with broad substrate

  • specificity


Mj in sequences X and Y

Aglu

Plantae

Fungi

At

XYL1

Pt Aglu

Tm

XYL

Sp Aglu

St MAL2

Anig aglA

Pp BAB3946

An AgdA

So Aglu

Ca GAM1

Bv Aglu

Soc GAM1

At Aglu-1

An agdB

Hv Aglu

Protista

Tp GAA

Hs GAA

Cj GAAII

Cj GAAI

Archaea

Ss xylS

Hs S/I-N

Hs S/I-C

Bt Aglu-III

Lv GAA

Ce AAA8317

Bh BAB0442

Aa GlcA

Lp XylQ

Sc

CAB8890

Tm

AAD3539

Animalia

Bacteria

0.1


  • Plant in sequences X and Y-amylases are located in different cellular compartments

    • Plastids (chloroplasts, amyloplasts)

    • Cytosol

    • Apoplast (cell wall space)

  • What is the function of the non-plastid forms?


Arabidopsis in sequences X and YAMY1

Clade I

Secreted

421-445 aa

rice 2A

barley A

barley B

morning glory

rice 3B

dodder

maize

adzuki bean

rice 3E

rice XP_472377

Arabidopsis AMY2

apple 10

cassava

apple 9

kiwifruit

apple 8

potato

plantain

Clade II

Cytosolic

407-414 aa

Clade III

Plastidic

877-906 aa

Arabidopsis AMY3

rice NP_916641


Homologous sequences in sequences X and Y (homologues)

Share a common ancestor

Paralogs

Homologues derived by gene duplication

Functions may vary

Look for differences

Orthologs

Homologues derived by speciation

Common function

Look for similarities


  • Use alignments to look for: in sequences X and Y

    • Structures important for common

      • functions (orthologs)

    • Structures important for unique

      • functions (paralogs)

    • Unusual structures


N in sequences X and Y

C

AMY1 has a three amino acid deletion

AtAMY1

3


Barley in sequences X and Y-amylase

Red: NHDTGST

Blue: VAEIW

Active site residues


Variation in the active site loop among plant and bacterial in sequences X and Y-amylases

AtAMY1


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