Transcript Evolution of Amino Acid Frequencies in Proteins

Evolution of Amino Acid
Frequencies in Proteins
Inferred Order of Introduction of Amino
Acids into the Genetic Code
Extant Genetic Code
From: http://www.millerandlevine.com/Code-Table-Rect.html
What Did this Table First Look Like?
Is not a “frozen accident”
There must have been earlier version
I.e., this code must have evolved
Hypothesis
Earliest proteins evolved
under an older version of
the genetic code
Current homologues to
those proteins can be
used to reconstruct these
proteins
Ancestral Sequence:
S P K A N E
Modern Descendents:
S
T
S
S
P
P
P
P
R
K
K
R
V
A
V
A
N
Q
N
N
D
E
E
E
What Might Show The Evolution?
Difference in amino acid composition between
ANCESTRAL and DESCENDENT proteins
We must find the earliest proteins from their modern
descendents
We must construct the ancestral sequences from their
modern descendents
Finding the Earliest Proteins
bcd
acd
Eubacteria
acdf
E. coli
Last
Universal
Ancestor
cdhij
Archaea
Eukaryotes
acde
bcdg
cdhijkl
cdhijmn
H. pylori
A. pyrnix
A. thaliana
S. cerivisae
cdhijmpq
H. sapiens
Reconstructed
cd
Finding the Earliest Proteins
Get protein families found in all branches of life
– BLAST genomes vs. genomes
– Find universal hits, i.e., proteins c and d
Yeast
Arabadopsis
Human
E. Coli
Alanyl-tRNA synthetase
Glycine hydroxymethyl
transferase
Seryl-tRNA synthetase
Transcription antiterminator
Chaperonin GroEL
RecA/RadA recombinase
…
Reconstructing the Earliest Proteins
Align all hits using
CLUSTALW 1.74
Infer ancestral
sequences using
families of proteins.
Modern Descendents:
S
T
S
S
P
P
P
P
R
K
K
R
V
A
V
A
N
Q
N
N
D
E
E
E
Ancestral Sequence?
S P K ? N E
Estimate Ancestral Composition
P(i|conserved) =
P(i)*P(conserved|i)/P(conserved)
Get ancestral composition by rearranging
equation and estimating terms
P(i) = ancestral composition =
P(i|conserved)*P(conserved)/P(conserved|i)
Count Descendant Composition
Obtain amino acid frequencies in families
Compare with estimated ancestral composition
Alanine:
Alanine:
Cysteine:
Cysteine:
Aspartate:
Aspartate:
Glutamate:
Glutamate:
Phenylalanine:
Phenylalanine:
Glycine:
Glycine:
Histidine:
Histidine:
Look for Significant Differences
Changes imply changes in genetic code
Relative changes also imply the sequence of
changes
Alanine:
Alanine:
Cysteine:
Cysteine:
Aspartate:
Aspartate:
Glutamate:
Glutamate:
Phenylalanine:
Phenylalanine:
Glycine:
Glycine:
Histidine:
Histidine:
Conclusion
Structure promoting amino acids increased
significantly over time
– Phenylalanine, tryptophan, tyrosine, and cysteine
Early proteins may not have been enzymes
Significant changes in protein function over time