Download Molecular Evolution Molecular differences accumulate linearly

Our mt genome can easily be aligned with those of other primates.
At most nucleotide positions (“sites”), everyone has the same nucleotide state.
But some sites are variable.
At these variable sites, some patterns are more common than others.
Here are the first 180 bp of the ~16.5 bp alignment for some famous hominoids.
Molecular Evolution
Alan R. Rogers
January 15, 2016
modern
Neander.
chimp
gorilla
GTTTATGTAGCTTACCTCCTCAAAGCAATACACTGAAAATGTTTAGACGGGCTCACATCA
GTTTATGTAGCTTACCTCCTCAAAGCAATACACTGAAAATGTTTAGACGGGCTCACATCA
GTTTATGTAGCTTACCCCCTCAAAGCAATACACTGAAAATGTTTCGACGGGTTTACATCA
GTTTATGTAGCTTACCTCCCCAAAGCAATACACTGAAAATGTTTCGACGGGCTCACATCA
**************** ** ************************ ****** * ******
modern
Neander.
chimp
gorilla
CCCCATAAACAAATAGGTTTGGTCCTAGCCTTTCTATTAGCTCTTAGTAAGATTACACAT
CCCCATAAACAAATAGGTTTGGTCCTAGCCTTTCTATTAGCTCTTAGTAAGATTACACAT
CCCCATAAACAAACAGGTTTGGTCCTAGCCTTTCTATTAGCTCTTAGTAAGATTACACAT
CCCCATAAACAAATAGGTTTGGTCCTAGCCTTTCTATTAACTCTTAGTAGGATTACACAT
************* ************************* ********* **********
modern
Neander.
chimp
gorilla
GCAAGCATCCCCGTTCCAGTGAGTTCACCCTCTAAATCACCACGATCAAAAGGAACAAGC
GCAAGCATCCCCATTCCAGTGAGTTCACCCTCTAAATCACCACGATCAAAAGGGACAAGC
GCAAGCATCCCCGCCCC-GTGAGT-CACCCTCTAAATCGCCATGATCAAAAGGAACAAGT
GCAAGCATCCCCGCCCCAGTGAGT-CACCCTCTAAATCACCACGATCAAAAGGAACAAGC
************
** ****** ************* *** ********** *****
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Molecular differences accumulate linearly
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Different proteins evolve at different rates
Amino Acid Substitutions per 100 Sites
Cyt C
Why linear?
●
Fibrinopeptides
Globins
80
60
Why do the slopes
differ?
40
●
20
●
●
●
●
●
●
100
200
300
400
500
Divergence Time (my)
600
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The neutral theory of molecular evolution
ADH in D.
melanogaster
Codon (above)
specifies an amino
acid (below).
Superscripts:
variant nucleotides.
Pos. 578: lysine →
threonine.
I
Most mutations are deleterious and are removed by selection.
I
Some are selectively neutral and may drift to fixation (i.e.
until they are 100% of the population)
I
Very rarely, advantageous mutations arise.
The neutral theory holds that case 2 predominates.
Implications
Why so many
3rd-position
changes?
I
Selection acts as a brake on molecular evolution.
I
Rate of molecular evolution approximately constant.
Why so few amino
acid differences?
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Why neutral evolution is linear
We expect evolution to be fast where selective constraint
is weak.
In a population of size N and mutation rate u, there are 2Nu new
mutations each generation.
A fraction 1/2N of these drifts to fixation.
Resulting rate: 2Nu ×
1
2N
Where is constraint weak?
= u.
Where is it strong?
Constant mutation rate ⇒ const rate of molecular evolution.
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The genetic code (DNA version)
First
Position
A
G
T
C
A
Phe
Phe
Leu
Leu
Leu
Leu
Leu
Leu
Ile
Ile
Ile
Met
Val
Val
Val
Val
Second Position
G
T
C
Ser
Tyr
Cys
Ser
Tyr
Cys
Ser Stop Stop
Ser Stop
Trp
Pro
His
Arg
Pro
His
Arg
Pro
Gln
Arg
Pro
Gln
Arg
Thr
Asn
Ser
Thr
Asn
Ser
Thr
Lys
Arg
Thr
Lys
Arg
Ala
Asp
Gly
Ala
Asp
Gly
Ala
Glu
Gly
Ala
Glu
Gly
ADH in D.
melanogaster
Third
Position
A
G
T
C
A
G
T
C
A
G
T
C
A
G
T
C
Codon (above)
specifies an amino
acid (below).
(adenine)
(guanine)
(thymine)
(cytosine)
Superscripts:
variant nucleotides.
Few 1st-position
changes are
synonymous.
Pos. 578: lysine →
threonine.
Weaker constraint
in 2nd position.
3rd position varies
most.
Weakest in
3rd-position.
Supports neutral
theory.
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Pig and human insulin genes
ADH sequence in 2 species
Line 1: DNA sequence in D.
melanogaster
Line 2: Nucleotides that differ in
D. erectus
Line 3: Amino acids that differ in
D. erectus
24 synonymous differences; 10
amino acid differences
I
Left portion (exon) is functional—codes for protein
I
Right portion (intron) isn’t.
I
Vertical lines show idential nucleotides in human and pig.
I
There are more differences in intron than in exon.
I
Nonfunctional DNA evolves faster.
Most species differences are
neutral.
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Pseudogenes evolve faster than functional genes
Synonymous versus nonsynonymous clocks
Within each protein,
synonymous (S) sites
evolve faster than
non-synonymous (N) sites.
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Morphological evolution doesn’t predict molecular
evolution
Molecular (transversion) differences in mtDNA
Frogs and opossums have changed little in many millions of years.
Yet their proteins and DNA evolve as fast as those of other
animals.
Bovid
Gibbon
Orang.
Goril.
Chimp.
Human
“The serological differences in albumins found among frogs are far
larger than morphological analysis would lead us to expect. Frogs
that are anatomically, and presumably physiologically, similar
enough to merit taxonomic distinction only at the species level
often exhibit differences in their albumins larger than those usually
seen between mammals placed in distinct families or suborders. By
contrast, the clock hypothesis appears to predict rather well.”
Mouse Bovid Gibbon Orang. Goril. Chimp.
91
83
69
90
65
18
85
71
19
15
86
71
18
16
5
89
70
19
15
4
3
(Hasegawa, Kishino, & Yano 1985)
(Wallace, Maxson, and Wilson, 1971)
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The molecular clock: a numerical example
Other topics
I
Human-Orang difference is 15 nucleotides in (say) 14 my, a
rate of r = 1.07 per my.
I
Human-Chimp difference is 4 nucleotides.
I
Estimating dates from molecular data.
I
Solve rt = 4 to get t = 3.7 my, an estimate of the
chimp-human separation time.
I
Caveats: saturation, purifying selection, metabolic rate,
generation time, calibration
This estimate is too low, because we failed to correct for multiple
mutations per nucleotide site in the orang-human comparison.
Nonetheless, it illustrates the logic.
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Summary
1. Molecular differences accumulate at roughly constant rate.
2. Evolution is fastest where selective constraint is weak.
3. Supports idea that most molecular evolution is neutral.
4. Does not imply that neutral evolution at level of organism.
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