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A Universal Trend of Amino Acid Gain and Loss in Protein Evolution

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Title: A Universal Trend of Amino Acid Gain and Loss in Protein Evolution


1
A Universal Trend of Amino Acid Gain and Loss in
Protein Evolution
Nature 433, 633 - 638
  • I. KING JORDAN, FYODOR A. KONDRASHOV,
    IVAN A. ADZHUBEI, YURI I. WOLF, EUGENE V. KOONIN,
    ALEXEY S. KONDRASHOV SHAMIL SUNYAEV

Song Yang, Journal Club 2005-02-28
2
A Mis-conception
  • It is assumed that the reciprocal flux of amino
    acid substitution are equal
  • Symmetrical substitution matrix are used for
    protein sequence alignment
  • It has never been tested

3
Motivation
  • Author amino acid composition of protein varies
    substantially between taxa ?
  • Theoretically, the composition of amino acid of
    protein should evolve
  • The question is to what extent it evolves?

COSB_2002_12_409-416
4
Methods
  • Directed substitution derived from orthologous
    proteins in triplet of closely related genomes
  • Data set 15 genome sets X 75 substitution pairs
    1,125 pairs

5
Data Set
6
Statistical Analysis
  • The reciprocal fluxes differed by a factor of gt
    1.5 for 575 of 1,125 pairs
  • Among them, 175 pairs are statistical significant
    (Plt0.05)
  • Multiple test Holms procedure (FEW, Family-Wise
    Error-rate)

7
Asymmetrical Substitution
8
Amino Acid Gainers and Losers
  • 5 strong gainers Cys, Met, His, Ser, Phe
  • 4 strong losers Pro, Ala, Glu, Gly
  • 4 weak gainers Asn, Thr, Ile, Val
  • 1 weak losers Lys
  • 6 random evolvers Arg, Gln, Trp, Leu, Tyr, Asp

9
Possible Errors
  • Multiple substitution False identification of
    amino acid transition
  • Conservative correction of multiple substitution
  • Closely related triplet genome set
  • Highly conserved proteins
  • Human nonsynonymous SNPs SNPs located in coding
    regions and resulting in amino acid variation in
    the protein products

10
Human Nonsynonymous SNPs
11
A Universal Trend ?
  • No other more plausible explaination
  • Comparing extant proteins with their
    reconstructed remote ancestors
  • Not GC or purine/pyrimidine content related

12
Extrapolation and Estimation
  • 2 substitute per protein site
  • 0.77 predicted by other method
  • Tendency of unbiased usage of codons
  • Loser-rich and gainer-poor amino acid composition
    of primordial proteins
  • Order by which amino acids were recruit to
    genetic code

13
Inferred Evolutionary Trajectories
14
My Suspicions
  • The amino acid asymmetric substitution could come
    from the difference of the frequencies in genomes
  • The tendency derived from closely related species
    (10 million years) cannot be extrapolated up to
    the last universal common ancestor.
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