molecular clocks

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Molecular Molecular clocksclocks

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Molecular clock?• The molecular clock hypothesis

was put forward by Zuckerkandl and Pauling in 1962.

• They noted that rates of amino acid replacements in animal hemoglobins were proportional to time of divergence—as judged from the fossil record.

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Molecular clocks?• Zuckerkandl and Pauling, therefore,

proposed that for any given protein, the rate of molecular evolution is approximately constant over time in all lineages.

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The molecular clock hypothesis

If proteins evolve at constant rates, then the number of substitutions between two sequences may be used to estimate divergence times.

This is analogous to the dating of geological times by radioactive decay.

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Example:

The rate of nonsynonymous substitution for -globin is

0.56 10–9 nonsynonymous substitutions per nonsynonymous site per year.

Rat and human -globins differ by 0.093 nonsynonymous substitutions per nonsynonymous site.

If the universal molecular-clock hypothesis is correct, then human and rat diverged from a common ancestor

0.093/2 0.56 10 –9 = 83 million years ago.

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Allan C. Wilson Morris Goodman

11The “The “sacrament”sacrament” of the straight line of the straight line

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Q: How to draw a straight line?A1: Have no more than two observation points.

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Q: How to draw a straight line?A2: With more than two observation points, use a very thick line.

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Q: How to draw a straight line?A3: With more than two observation points, deny the accuracy of the measurements on one or both axes.

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Relative Rate TestsRelative Rate Tests

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Sarich & Wilson’s Sarich & Wilson’s TestTest

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KAB = KOA + KOB

KAC = KOA + KOC

KBC = KOB + KOC

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KOA = (KAC + KAB – KBC)/2KOB = (KAB + KBC – KAC)/2KOC = (KAC + KBC – KAB)/2

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If the molecular clock hypothesis is correct, thenKAC – KBC = 0

21Not significantly different from 0

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No such difference is seen at No such difference is seen at nonsnonsyynonnonyymousmous sites, indicating that sites, indicating that mutational differences, rather than mutational differences, rather than selectional differences, are involved.selectional differences, are involved.

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The results of the relative rate test depend on knowledge of true tree.

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Tests involving Tests involving duplicated genesduplicated genes

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KA1B1=KAA1

+KOA +KOB+KBB1

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KA2B2=KAA2

+KOA +KOB+KBB2

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If A1 evolves at the same rate as A2, and B1 evolves at the same rate as B2, then KA1B1

−KA2B2=0

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34A = adult; E = embryonic; F = fetal

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Relative rate tests have Relative rate tests have shown that there is shown that there is nono universal molecular universal molecular clock.clock.

However, sufficiently accurate However, sufficiently accurate local clocks may exist.local clocks may exist.

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fastslow

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Mutation rate per site per year versus genome size(Gago S, Elena SF, Flores R, Sanjuán R. Extremely high mutation rate of a hammerhead viroid. 2009. Science 323:1308.)

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The ranking of organisms started with the Aristotelian Scala Naturae…

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… … and was used by and was used by Linnaeus in his Linnaeus in his

Systema Naturae.Systema Naturae.

Primates (humans and monkeys)Primates (humans and monkeys)

Secundates (mammals)Secundates (mammals)

Tertiates (all others)Tertiates (all others)

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In the literature one often encounters the adjective “primitiveprimitive” attached to the name of an organism. For example, sponges are defined as “primitiveprimitive.”

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Humans, on the other hand, are always referred to as “advancedadvanced.”

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44Advanced Primitive

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Causes of variation in substitution rates among evolutionary lineagesThe factors most commonly invoked to explain the differences in the rate of substitution among lineages are:

(1) replication-dependent factors, i.e.,

mutation.mutation. (2) replication-independent factors, i.e.,

selection.selection.

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Generation Time

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Rates of evolution tend to Rates of evolution tend to correlate with generation correlate with generation times.times.

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Metabolic rate = amounts of O2

consumed per weight unit per time unit.

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micemice whaleswhales

metabolic-rate effectmetabolic-rate effect

sharkssharksnewtsnewts

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Rates of evolution tend to Rates of evolution tend to correlate with metabolic correlate with metabolic rates.rates.

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Generation times tend to Generation times tend to correlate with metabolic correlate with metabolic rates.rates.

The big ones are the slow The big ones are the slow ones. ones.

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Animals

Plants

HIGHLOW

Organelles: Mutation RatesOrganelles: Mutation Rates

nucleusnucleus mitochondriamitochondria

HIGHLOWnucleusnucleusmitochondriamitochondria chloroplastchloroplast

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Evolution of RNA viruses:Evolution of RNA viruses:RNA VIRUSES evolve at rates that are about 106 times faster than those of DNA organisms. Therefore, significant numbers of nucleotide substitutions accumulate over short time periods, and differences in nucleotide sequences between strains isolated at relatively short time intervals are detectable. This property allows for a novel approach to estimating evolutionary rates.

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Model tree for RNA viruses: l1 and l2 = numbers of substitutions on the branches leading to isolates 1 and 2, respectively. Sequence 1, which was isolated at t1, was collected t years earlier than sequence 2, which was isolated at t2. r = rate of substitution per site per year

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l2 – l1 = rt2 – rt1 = rtl2 – l1 = d23 – d13

r =d23−d13

t

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Example:

Two strains of the HIV1 virus, denoted as 1 and 2 were isolated from a two-year-old child on 3 October 1984 and 15 January 1985, respectively. The child was presumed to have been infected once perinatally by her mother by a single strain of HIV1.

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03 Dec. 198415 Jan. 1985

Reference

t = 3.4 months (0.28 year)

d13 = 0.0655

d23 = 0.0675

a = 7.1 10–3 substitutions/site/year

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Tempo of Evolution:Tempo of Evolution:

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Punctuated equilibrium (Punk eek)Niles Eldredge & Steven J. Gould (1972).

Punctuated equilibrium: An alternative to phyletic gradualism. pp. 82-115. In: T. J. M. Schopf (ed.) Models in Paleobiology, Freeman, Cooper & Co., San Francisco.

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“... it is probable that the periods, during which each [species] underwent modification, though many and long as measured by years, have been short in comparison with the periods during which each remained in an unchanged condition.”

Charles Darwin, from the final 6th edition (1872) of On the Origin of Species

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change

time

Phyletic gradualism

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change

time

Punctuated equilibria associated with speciation events

stasisrevolution

speciation

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time

Punctuated equilibria disassociated from speciation events

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A phylogenetic treefor the growth-hormone

gene in mammals

During most mammalian evolution, growth-hormones evolved quite slowly (~0.3 10–9 replacements per site per year). There are, however, two rate increases: a 40-fold increase prior to primateprimate divergence, and a 20-fold increase prior to ruminantruminant divergence.

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Possible explanations for the increased rates in ruminants and primates:

(1) an increase inan increase in mutation ratemutation rate(2) positive selectionpositive selection(3) relaxation of purifying relaxation of purifying selection selection

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Rates of amino-acid replacement (×109±stndrderror)ndthertioofnonsynonym ous(KA)tosynonymous(KS)

substitutioningrowth-hormonegenesduringmm mlin

evolution

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Rteofmi no-cid

Phse replcem ent KA/KS_________________________________________________________

Slowphse 0.3±0.1 0.03Rum inntrpidphse 5.6±1.4 0.30Prim terpidphse 10.8±1.3 0.49

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Mindell, Sykes & Graur Test

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IS THERE A RELATIONSHIP IS THERE A RELATIONSHIP BETWEEN BETWEEN MOLECULARMOLECULAR RATES OF EVOLUTION & RATES OF EVOLUTION & MORPHOLOGICALMORPHOLOGICAL RATES RATES

OF EVOLUTION?OF EVOLUTION?

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A living fossil: Limulus polyphemus (Atlantic horseshoe crab)

fossil (500 mya) extant

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Blue shark (Prionace glauca) Alligator (Alligator mississippiensis)

Molecularly fast-evolving lineages

Living fossils

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Molecularly slow-evolving lineages

Yellow mud turtle (Kinosternon flavescens)

Living fossils

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IS THERE A RELATIONSHIP IS THERE A RELATIONSHIP BETWEEN BETWEEN MOLECULARMOLECULAR RATES OF EVOLUTION & RATES OF EVOLUTION & MORPHOLOGICALMORPHOLOGICAL RATES RATES

OF EVOLUTION?OF EVOLUTION?

NO!NO!

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Some scientists have even Some scientists have even suggested that the lack of suggested that the lack of relationship between the two relationship between the two levels of description is so levels of description is so total as to deserve to be total as to deserve to be called:called:

““The Big Divorce”The Big Divorce”