Research on Mitochondrial Genomes Lectures for 4Y03

1
Research on Mitochondrial GenomesLectures for
4Y03

• Paul Higgs
• Dept. of Physics, McMaster University, Hamilton,
  Ontario.

Supported by Canada Research Chairs and BBSRC
2

1. Building a database for mitochondrial genomes.
2. Large scale - gene order evolution.
3. Medium scale sequence evolution. Molecular
   phylogenetics.
4. Small scale mutation and selection. Variation
   in base and amino acid frequencies. Codon usage.
5. Genetic code evolution

People 1. Wenli Jia, Bin Tang, Daniel Jameson
2. Howsun Jow, Magnus Rattray, Cendrine Hudelot,
Vivek Gowri-Shankar, Xiaoguang Yang 3. Wei Xu,
Daniel Jameson 4. Daniel Urbina, Wenli Jia. 5.
Supratim Sengupta
3
Mitochondria are organelles inside eukaryotic
cells. They are the site of oxidative
phosphorylation and ATP synthesis. They contain
their own genome distinct from the DNA in the
nucleus.
Typical animal mitochondrial genomes are short
and circular (16,000 bases). They usually
contain 2 rRNAs 22 tRNAs 13 proteins
4
LOCUS NC_001922 16646 bp
DNA circular VRT 20-SEP-2002 DEFINITION
Alligator mississippiensis mitochondrion,
complete genome. ACCESSION NC_001922 VERSION
NC_001922.1 GI5835540 KEYWORDS . SOURCE
mitochondrion Alligator mississippiensis
(American alligator) ORGANISM Alligator
mississippiensis Eukaryota Metazoa
Chordata Craniata Vertebrata Euteleostomi
Archosauria Crocodylidae Alligatorinae
Alligator. REFERENCE 1 (bases 1 to 16646)
AUTHORS Janke,A. and Arnason,U. TITLE The
complete mitochondrial genome of Alligator
mississippiensis and the separation
between recent archosauria (birds and
crocodiles) JOURNAL Mol. Biol. Evol. 14 (12),
1266-1272 (1997) MEDLINE 98066357 PUBMED
9402737 FEATURES Location/Qualifiers
source 1..16646
/organism"Alligator mississippiensis"
/organelle"mitochondrion"
/mol_type"genomic DNA"
/db_xref"taxon8496"
/tissue_type"liver"
/dev_stage"adult" rRNA 1..976
/product"12S ribosomal RNA"
tRNA 977..1044
/product"tRNA-Val"
/anticodon(pos1009..1011,aaVal) rRNA
1046..2635
/product"16S ribosomal RNA" tRNA
2636..2710
/product"tRNA-Leu"
/note"codons recognized UUR"
/anticodon(pos2672..2674,aaLeu) gene
2711..3676
/gene"ND1" CDS 2711..3676
/gene"ND1"
An example of a GenBank file Complete
mitochondrial genome of the Alligator
1 caacagactt agtcctggtc ttttcattag
ctagtactca acttatacat gcaagcatcc 61
gcgaaccagt gagaacaccc tacaagtctg acagacgaat
ggagccggca tcaggcacat 121 caaccgatag
cccaaaacgc ctagcccagc cacaccccca agggtctcag
cagtgattaa 181 ccttaaacca taagcgaaag
cttgatttag ttagagtaga tatagaggcg gtcaactctc
241 gtgccagcaa ccgcggttag acgaaaacct caagttaatt
gacaaacggc gtaaattgtg 301 gctagaactc
tatctccccc attagtgcag atacggtatc acagtagtga
taaacttcat 361 cacaccgcaa acatcaacac
aaaactggcc ctaatctcaa agatgtactc gattccacga
421 aagctgagaa acaaactggg attagatacc ccactatgct
cagcccttaa cattggtgta 481 gtacacaaca
gactaccctc gccagagaat tacgagcccc gcttaaaact
caaaggactt 541 gacggcactt taaacccccc
tagaggagcc tgtcctataa tcgacagtac acgttacacc
601 cgaccacctt tagcctactc agtctgtata ccgccgtcgc
aagcccgtcc catttgaggg 661 aaacaaaacg
cgcgcaacag ctcaaccgag ctaacacgtc aggtcaaggt
gcagccaaca 721 aggtggaaga gatgggctac
attttctcaa catgtagaaa tattcaacgg agagccctat
781 gaaatacagg actgtcaaag ccggatttag cagtaaactg
ggaaagaata cctagttgaa 841 gtcggtaacg
aagtgcgtac acaccgcccg tcaccctcct cgaacccaac
aaaatgccca 901 aacaacaggc acaatgttgg
gcaagatggg gaaagtcgta acaaggtaag cgtaccggaa
961 ggtgcacttg gaacatcaaa atgtagctta aatttaaagc
attcagttta cacctgaaaa 1021 agtcccacca
tcggaccatt ttgaaaccca tatctagccc tacctccttt
caacatgctt
5
OGRe ( Organellar Genome Retrieval) is a
relational database.
available at http//ogre.mcmaster.ca More than
800 complete animal mitochondrial
genomes. Efficient means of storage and retrieval
of information. Uses PostgreSQL Schema defines
relationships between different types of
information.
6
The OGRe front page
http//ogre.mcmaster.ca Sequence information for
OGRe is taken from GenBank. We aim to keep up to
date with publicly available animal mitochondrial
genomes.
7
Species may be selected individually from an
alphabetical list
Or taxa may be selected from a hierarchy. Here
the Arthropods have been expanded and the
Myriapods and Crustaceans have been selected
8
Large Scale Evolution of Gene Order in Whole
Genomes
On the ogre web site, a visual comparison can be
made of any two selected species. Colour is used
to indicate conserved blocks of genes.
Alligator and Bird genomes differ by interchange
of two tRNA genes (red and yellow)
and by translocation of the two genes in the
blue block.
9
Genome reshuffling mechanisms Inversions
C
-C -B
B
A D
A
D
10
Example of an inversion
Example of a translocation
11
The T and F genes are duplicated in Cordylus
warreni. If the first T and the second P were
deleted, the relative position of T and P would
change.
12
Sometimes things go crazy .
Drosophila and Thrips are both insects yet there
are 30 breakpoints for only 37 genes i.e. almost
nothing in common.
13
OGRe contains gene orders as strings. This allows
searching and comparison. 231 unique gene orders
have been found in 858 species. The standard
vertebrate order is shared by 398 species
(including humans). There are many other species
with unique gene orders. Some species conserve
gene order over 100s of millions of years. Others
get scrambled in a few million. Still to do (new
project) - estimate relative rates of
different rearrangement processes - predict most
likely ancestral gene orders - use gene order
evidence in phylogenetics
14
Medium Scale Sequence Alignments and
Phylogenetics Part of sequence alignment of
Mitochondrial Small Sub-Unit rRNA Full gene is
length 950 11 Primate species with mouse as
outgroup
15
69 Mammals with complete motochondrial
genomes. Used two models simulatneously Total
of 3571 sites 1637 single sites 967
pairs Hudelot et al. 2003
16
Afrotheria / Laurasiatheria
Striking examples of convergent evolution
17
Arthropod phylogenetics Very difficult due to
strong variation in rates of evolution between
species. tRNA tree branch lengths optimized on
fixed consensus topology Long branch species are
problematic if tree is not fixed.
Images coutesy of University of Nebraska, Dept.of
Entomology. http//entomology.unl.edu/images/
18
protein tree branch lengths optimized on fixed
consensus topology
Same species are on long branches in proteins as
in RNAs
Images coutesy of University of Nebraska, Dept.of
Entomology. http//entomology.unl.edu/images/
19
Relative rate test for sequence evolution -
Templeton
Three aligned sequences with 0 known to be the
outgroup. Test whether rates of evolution in
branch 1 and branch 2 are equal. m1 number of
sites where 0 and 2 are the same and 1 is
different. m2 number of sites where 0 and 1 are
the same and 2 is different.
0 1 2
Calculate
Should follow a chi squared distribution with one
degree of freedom. Many pairs of related species
found to have different rates in the
mitochondrial sequences.
20
Gene Order sometimes gives evidence of
phylogenetic relationships
The gene order of the ancestral arthropod is
thought to be the same as that of the horseshoe
crab Limulus. Image courtesy of Marine Biology
Lab, Woods Hole. www.mbl.edu/animals/Limulus
The same translocation of tRNA-Leu is found in
insects and crustaceans but not myriapods and
chelicerates. Strong argument for the group
Pancrustacea ( insects plus crustaceans)
Limulus and the fruit fly, Drosophila, differ by
a single translocation of a tRNA-Leu gene (shown
in yellow and marked by an arrow).
21
Moderately rearranged
Completely scrambled
22
Very High
High
Species ranked according to breakpoint distance
from ancestor.
Medium
Low
23
R 0.99
R 0.59
R 0.53
R 0.69
24
Highly rearranged genomes have highly divergent
sequences. Rates of sequence evolution and genome
rearrangement are correlated. Both are very
non-clocklike.
There are many species where only tRNAs have
changed position. Species with highly reshuffled
tRNAs have high rates of sequence evolution in
both tRNAs and proteins.
25
Relative rate of genome rearrangement (Xu et al
2006)
Three gene orders with 0 known to be the
outgroup. Test whether rates of rearrangement in
branch 1 and branch 2 are equal. n1 number of
gene couples in 0 and 2 but not in 1 i.e. New
breakpoint in 1 n2 number of gene couples in 0
and 1 but not in 2 i.e. New breakpoint in 2
0 1 2
Calculate
Should follow a chi squared distribution with one
degree of freedom. We took pairs where there was
a significant difference in rearrangement rates
(?n2 was large) and showed that there was a
significant difference in substitution rates too
(?m2 was large).
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Good Guys
Bad Guys
Gene order is sometimes a strong phylogenetic
marker but the Bad Guys are problematic in gene
order analysis as well as phylogenetics. Why
does the evolutionary rate speed up in these
isolated groups of species? Why to tRNA genes
move more frequently? What are the relative rates
of inversion and translocation?
Credits Daniel Jameson/ Bin Tang Database
design and management Daniel Urbina Base and
Amino Acid Frequencies Wei Xu Gene Order
Analysis and Arthropod Phylogenies
27
Small Scale Evolution Variation in Frequencies
of Bases and Amino Acids
The two strands of DNA are complementary. Freq of
A on one strand Freq of T on the other Freq of
C on one strand Freq of G on the other
If the two strands are subject to the same
mutational processes then the freq of any base
should be equal (statistically) on both
strands. This means that A T and C G on any
one strand. In this case base frequencies can be
described by a single variable GC content.
BUT mitochondrial genomes have an asymmetrical
replication process. The two strands are not
equivalent. The frequencies of bases on the two
strands are not equal. On any one strand the
frequencies of the four bases may vary
independently.
28
Mitochondrial genome replication
Figure from Faith Pollock (2003) Genetics
Rank genes in order of increasing time spent
single stranded COI lt COII lt ATP8 lt ATP6 lt COIII
lt ND3 lt ND4L lt ND4 lt ND1 lt ND5 ltND2 lt Cytb ND6 is
on the other strand
29
The Genetic Code maps the 64 DNA codons to the 20
amino acids. (This version applies to Vertebrate
Mitochondria)
SECOND POSITION SECOND POSITION SECOND POSITION SECOND POSITION
T C A G THIRD POSITION
F I R S T P O S I T I O N T TTT F 1 TTC F TCT S TCC S 6 TCA S TCG S TAT Y 10 TAC Y TGT C 17 TGC C T C A G
F I R S T P O S I T I O N T TTA L 2 TTG L TCT S TCC S 6 TCA S TCG S TAA Stop TAG Stop TGA W 18 TGG W T C A G
F I R S T P O S I T I O N C CTT L CTC L CTA L CTG L CCT P CCC P 7 CCA P CCG P CAT H 11 CAC H CGT R CGC R 19 CGA R CGG R T C A G
F I R S T P O S I T I O N C CTT L CTC L CTA L CTG L CCT P CCC P 7 CCA P CCG P CAA Q 12 CAG Q CGT R CGC R 19 CGA R CGG R T C A G
F I R S T P O S I T I O N A ATT I 3 ATC I ACT T ACC T 8 ACA T ACG T AAT N 13 AAC N AGT S 20 AGC S T C A G
F I R S T P O S I T I O N A ATA M 4 ATG M ACT T ACC T 8 ACA T ACG T AAA K 14 AAG K AGA Stop AGG Stop T C A G
F I R S T P O S I T I O N G GTT V GTC V 5 GTA V GTG V GCT A GCC A 9 GCA A GCG A GAT D 15 GAC D GGT G GGC G 21GGA GGGG G T C A G
F I R S T P O S I T I O N G GTT V GTC V 5 GTA V GTG V GCT A GCC A 9 GCA A GCG A GAA E 16 GAG E GGT G GGC G 21GGA GGGG G T C A G
4-codon families where the third position is
synonymous
30
Base frequencies at FFD sites in each gene
(averaged over mammals)
Deamination C to U and A to G on the heavy strand
31
Base frequencies at FFD sites are controlled by
mutation. Base frequencies at 1st and 2nd
positions are influenced by mutation and selection
Model fitting (Data from Fish) assume a
fraction of fixed sites and a fraction of neutral
sites. Selection at 1st position is weaker than
at 2nd
32
Mutation pressure is sufficient to cause change
in amino acid frequencies.
Second Position Second Position Second Position Second Position
T C A G Third Pos.
F i r s t P o s i t i o n T F 1 F S S 6 S S Y 10 Y C 17 C T C A G
F i r s t P o s i t i o n T L L L 2 L L L S S 6 S S Stop Stop W 18 W T C A G
F i r s t P o s i t i o n C L L L 2 L L L P P 7 P P H 11 H R R 19 R R T C A G
F i r s t P o s i t i o n C L L L 2 L L L P P 7 P P Q 12 Q R R 19 R R T C A G
F i r s t P o s i t i o n A I 3 I T T 8 T T N 13 N S 20 S T C A G
F i r s t P o s i t i o n A M 4 M T T 8 T T K 14 K Stop Stop T C A G
F i r s t P o s i t i o n G V V 5 V V A A 9 A A D 15 D G G 21GG T C A G
F i r s t P o s i t i o n G V V 5 V V A A 9 A A E 16 E G G 21GG T C A G
33
Slopes of the amino acid freq v base freq show
the response of the amino acid to mutational
pressure. Black fish White mammals Amino
acids in the first two columns of the code have
larger slopes.
34
Physical Properties of Amino Acids
Vol. Bulk. Polarity pI Hyd.1 Hyd.2 Surface Area Fract. Area
Ala A 67 11.50 0.00 6.00 1.8 1.6 113 0.74
Arg R 148 14.28 52.00 10.76 -4.5 -12.3 241 0.64
Asn N 96 12.28 3.38 5.41 -3.5 -4.8 158 0.63
Asp D 91 11.68 49.70 2.77 -3.5 -9.2 151 0.62
Cys C 86 13.46 1.48 5.05 2.5 2.0 140 0.91
Gln Q 114 14.45 3.53 5.65 -3.5 -4.1 189 0.62
Glu E 109 13.57 49.90 3.22 -3.5 -8.2 183 0.62
Gly G 48 3.40 0.00 5.97 -0.4 1.0 85 0.72
His H 118 13.69 51.60 7.59 -3.2 -3.0 194 0.78
Each Amino Acid is a point in 8-d space. dij
Euclidean distance between a.a. i and j in 8-d
space.
35
Principal Component Analysis Projects the 8-d
space into the two most important dimensions.
Big
Small
Hydrophobic
Hydrophilic
36
Responsiveness measures how much an amino acid
frequency varies in response to mutational
pressure Root mean square of 8 slopes for
each amino acid (i.e. 4 bases x 2 data sets)
Proximity measures how similar the neighbouring
amino acids are in the genetic code Mean of
1/d for accessible amino acids e.g. Prox
(T)
37
Responsiveness and Proximity are highly
correlated. R 0.87 (p lt 10-6)
An amino acid frequency responds to mutational
pressure more easily if there are neighbouring
amino acids with similar physical properties.
Urbina et al. (2006) J.
Mol. Evol.
38
(No Transcript)
39
Frequency ratios
Codon bias seems to be a dinucleotide mutational
effect in mitochondria, rather than an effect of
translational selection. CpG effect....
(increased rate of C to U mutations in CG
dinucleotides. Expect high UG and CA) DNA binding
proteins....
40
Changes in tRNA content of genomes from bacteria
to mitochondria
Only one type of tRNA remains for each codon
family in human mitochondria. Still need 2 tRNAs
for Leu and Ser. Therefore 22 in total.
denotes intracellular parasite or endosymbiont.
Small size genomes in bacteria also have reduced
numbers of tRNAs.
41
Evolution of the Genetic CodeBefore and After
the LUCA

1. The genetic code evolved to its canonical form
   before the Last Universal Common Ancestor of
   Archaea, Bacteria and Eukaryotes - gt3 billion
   years ago. It appears to be highly optimized. How
   did it get to be this way?
2. Numerous small changes have occurred to the
   canonical code since then. What is the mechanism
   of codon reassignment?

42
Codon Reassignment The Genetic code is variable
in mitochondria (and also some cases of other
types of genomes)
Second Position Second Position Second Position Second Position
U C A G Third Pos.
F i r s t P o s i t i o n U F F L L S S S S Y Y Stop Stop C C Stop W U C A G
F i r s t P o s i t i o n C L L L L P P P P H H Q Q R R R R U C A G
F i r s t P o s i t i o n A I I I M T T T T N N K K S S R R U C A G
F i r s t P o s i t i o n G V V V V A A A A D D E E G G GG U C A G
UGA Stop to Trp AUA Ile to Met CUN Leu to Thr CGN
Arg to unassigned AGR Arg to Ser to Stop/Gly
etc.....
But how can this happen? It should be
disadvantageous.
43
Example 1 AUA was reassigned from Ile to Met
during the early evolution of the mitochondrial
genome.
Before Codon Anticodon Notes
Ile Ile Ile Met AUU AUC AUA AUG GAU k2CAU CAU G in the wobble position of the tRNA-Ile can pair with U and C in the third codon position Bacteria and some protist mitochondria possess another tRNA-Ile with a modified base that translates AUA only. The tRNA-Met translates AUG only.
After Codon Anticodon Notes
Ile Ile Met Met AUU AUC AUA AUG GAU UAU or f5CAU In animal mitochondria the k2CAU tRNA has been deleted. There is a gain of function of the tRNA-Met by a mutation or a base modification
44
Example 2 UGA was reassigned from Stop to Trp
many times (12 times in mitochondria).
Before Codon Anticodon Notes
Stop Trp UGA UGG RF CCA Release Factor recognizes UGA codon. Normal tRNA-Trp translates only UGG codons.
After Codon Anticodon Notes
Trp Trp UGA UGG UCA In animal mitochondria (and elsewhere) there is a gain of function of the tRNA-Trp via mutation or base modification so that it translates both UGG and UGA.
45
The GAIN-LOSS framework (Sengupta Higgs,
Genetics 2005) LOSS deletion or loss of
function of a tRNA or RF GAIN gain of a new
tRNA or a gain of function of an existing one.
Mutations in coding sequences
46
Four possible mechanisms of codon reassignment.
1. Codon Disappearance - The codon disappears.
The order of the gain and loss is irrelevant. For
the other three mechanisms the codon does not
disappear. 2. Ambiguous Intermediate The gain
happens before the loss. There is a period when
the gain is fixed in the population and
translation is ambiguous. 3. Unassigned Codon
The loss happens before the gain. There is a
period when the loss is fixed in the population
and the codon is unassigned. 4. Compensatory
Change The gain and loss are fixed in the
population simultaneously (although they do not
arise at the same time). There is no intermediate
period between the old and the new codes. - cf.
theory of compensatory substitutions in RNA
helices. Sengupta Higgs (2005) showed that all
four mechanisms work in a population genetics
simulation
47
Summary of Codon Reassignments in Mitochondria
Codon reassignment No. of times Can this be explained by GC?AU mutation pressure? Change in No. of tRNAs Is mispairing important? Mechanism
UAG Stop ? Leu 2 G ? A at 3rd pos. 1 No CD
UAG Stop ? Ala 1 G ? A at 3rd pos. 1 No CD
UGA Stop ? Trp 12 G ? A at 2nd pos. 0 Possibly. CA at 3rd pos. CD
CUN Leu ? Thr 1 C ? U at 1st pos. 0 No CD
CGN Arg ? Unass 5 C ? A at 1st pos. -1 No CD
AUA Ile ? Met or Unassigned 3 / 5 No -1 Yes. GA at 3rd pos. UC
AAA Lys ? Asn 2 No 0 Yes. GA at 3rd pos. AI
AAA Lys ? Unass 1 No 0 Possibly. GA at 3rd pos. UC or AI
AGR Arg ? Ser 1 No -1 Yes. GA at 3rd pos. UC
AGR Ser ? Stop 1 No 0 No AI(b)
AGR Ser ? Gly 1 No 1 No AI(b)
UUA Leu ? Stop 1 No 0 No UC or AI
UCA Ser ? Stop 1 No 0 No UC or AI
CD mechanism explains disappearance of stop
codons because they are rare initially. Only a
few examples of CD for sense codons. UC and AI
are important for sense codons.
48
Three examples in yeasts (Mutation pressure GC to
AU)
CUN is rare (replaced by UUR) CUN Leu to Thr
Second Position Second Position Second Position Second Position
U C A G Third Pos.
F i r s t P o s i t i o n U F F L L S S S S Y Y Stop Stop C C Stop W U C A G
F i r s t P o s i t i o n C L L L L P P P P H H Q Q R R R R U C A G
F i r s t P o s i t i o n A I I I M T T T T N N K K S S R R U C A G
F i r s t P o s i t i o n G V V V V A A A A D D E E G G GG U C A G
CGN is rare (replaced by AGR) CGN Arg codons
become unassigned.
AUA and AUU common and AUC is rare Nevertheless
AUA is reassigned to Met. Codon does not disappear
49
Leu and Arg codons in yeasts Codon Disappearance
causes reassignments
LeuCUN Leu UUR Arg CGN Arg AGR
S 53 192 7 33
Y. 44 618 0 75
C 3 279 12 29
C 132 397 47 26
C 66 547 39 45
P 25 714 18 67
K 0 286 0 48
C 11 294 1 45
S 33 333 7 49
S 19 274 0 40
S 22 300 0 46
CUN Thr. Unusual tRNA-Thr present instead
of tRNA-Leu CGN unassigned. tRNA-Arg is
deleted
50
AUA Ile to Met in Yeasts
codon anticodon AUU Ile GUA AUC Ile AUA
Ile K2CAU AUG Met CAU
51
Reassignments in Metazoa
Loss of tRNA-Ile(CAU) but AUA remains Ile Loss of
tRNA-Arg(UCU) and AGR Arg -gt Ser
Loss of many tRNAs import from cytoplasm
AUA Ile -gt Met
AGR Ser -gt Stop
AGR Ser -gt Gly
AAA Lys -gt Asn
AAA Lys -gt unassigned
52
AGR in Metazoa One loss of tRNA-Arg with
several responses.
Second Position Second Position Second Position Second Position
U C A G Third Pos.
F i r s t P o s i t i o n U F F L L S S S S Y Y Stop Stop C C Stop W U C A G
F i r s t P o s i t i o n C L L L L P P P P H H Q Q R R R R U C A G
F i r s t P o s i t i o n A I I I M T T T T N N K K S S R R U C A G
F i r s t P o s i t i o n G V V V V A A A A D D E E G G GG U C A G
codon anticodon AGU Ser GUA AGC Ser AGA
Arg UCU AGG Arg

• AGR can become
• Ser/Unass (e.g Arthropods)
• Stop (e.g. Vertebrates)
• Gly (e.g. Urochordates)

53
Evolution of the canonical code - Before the LUCA
The canonical code seems to be optimized to
reduce the effects of translational and
mutational errors. Neighbouring codons code for
similar amino acids.
C
LI
F
W
M
Y
V
PT
A
HQ
SG
NK
R
E
D
Woeses polar requirement scale Measure
difference between amino acid properties by how
far apart they are on this scale.
54
Cost function g(a,b) for replacing amino acid a
by amino acid b e.g. difference in Polar
Requirement
rij rate of mistaking codon i for codon j
1 for single position mistakes, 0 otherwise E
measure of error associated with a code Generate
random codes by permuting the 20 amino acids in
the code table E is smaller for the canonical
code than for almost all random codes.
55
Principal Component Analysis Projects the 8-d
space into the two most important dimensions.
Big
Small
Hydrophobic
Hydrophilic
56
Modified codes show that the Canonical code could
have changed as it evolved not completely a
frozen accident. Possibility of competition
between organisms with different codes natural
selection. Early codes had lt20 amino acids (???).
Gradual increase in complexity. Increased
repertoire of amino acids gives more protein
functions.
Order of addition Astrobiology - which amino
acids were common on early Earth?
57
Prebiotic synthesis of amino acids

• Amino acids are found in
• Meteorites
• Atmospheric chemistry experiments (Miller-Urey)
• Hydrothermal synthesis
• Icy dust grains in space
• Rank amino acids in order of decreasing frequency
  in 12 observations. Derive mean ranking.
• G A D E V S I L P T (found non-biologically -
  early amino acids)
• K R H F Q N Y W C M (not found non-biologically
  late amino acids)

58
Early and Late amino acids are determined by
thermodynamics
59
Positions of early and late amino acids.... What
does this mean?
Second Position Second Position Second Position Second Position
U C A G Third Pos.
F i r s t P o s i t i o n U F F L L S S S S Y Y Stop Stop C C Stop W U C A G
F i r s t P o s i t i o n C L L L L P P P P H H Q Q R R R R U C A G
F i r s t P o s i t i o n A I I I M T T T T N N K K S S R R U C A G
F i r s t P o s i t i o n G V V V V A A A A D D E E G G GG U C A G
F F
Maybe only 2nd position was relevant
initially. Late amino acids took over codons
previously assigned to amino acids with similar
properties.
M
60
Other points Column structure suggests that
translational errors were more important than
mutational errors (tRNA structure/RNA
world) Precursor-product pairs tend to be
neighbours (but doubts over statistical
significance). Maybe late amino acids took over
codons previously assigned to their biochemical
precursors. Direct chemical interactions between
RNA motifs and amino acids (stereochemical
theory). In vitro selection experiments suggest
binding sites of aptamers preferentially contain
codon and anticodon sequences.