Download Molecular Evolution

Chapter 23 - Molecular evolution:
Types of questions:
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How do genomes, DNA, and protein sequences evolve?
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Dynamics and mode of change
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Rates of change
How are genes and organisms evolutionarily related?
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Phylogenetic systematics/building trees & networks
How do species emerge?
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Species concepts (allopatric/parapatric/sympatric)
Different time scales:
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Short-term: ‘population genetics’ tends to focus on genetic changes
between generations and within species or between very closely
related species.
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Microevolution
Long-term: ‘molecular systematics’ tends to focus on genetic
changes over many generations; departures from Hardy-Weinberg
equilibrium can become significant, leading to speciation.
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Macroevolution
http://www.talkorigins.org/faqs/macroevolution.html
Some basics:
Homology = refers to a structure, behavior, or other character of two
taxa that is derived from the same or equivalent feature of a
common ancestor.
Some basics:
Homology also applies to nucleotide sequences:
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Excellent example of positional vs. character homology
GTACCT
G-ATCT
1.
Four of six nucleotide positions have undergone no change.
2.
A substitution has occurred at position 4.
3.
Insertion/deletion has occurred in one sequence at position 2.
Sequence alignment:
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Rapid sequence divergence or divergence over many generations
can leave little in common between two sequences and make
alignment difficult or impossible.
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Indels ~ may be impossible to distinguish between an insertion in
one sequence and a deletion in another sequence.
example: mtDNA 12S rRNA in six different genera
CCACCT-GT---TTCAAAA-CTCAGGCCTT
TCACCTAGC---TCCAAA--C-TAGGCCTT
CTGCCT-AC---TTCCC---C-CAGGCCTT
TCGCCT-AC---T-CAA---C-CAGGCTTT
TCGCCT-ACATTTTCCC---C-CAGGCTTT
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Many alignment methods exist; all use algorithms that seek to
maximize the number of possible matching nucleotides or amino
acids and minimize the number of indels.
© Kathlyn Bailey
Models of nucleotide substitution:
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Jukes-Cantor (1969)
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Alignment of sequences with many differences underestimates the
actual number of substitutions.
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PC(t) = 1/4 + (3/4)e-4t
 = rate of substitution
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# substitutions/site =
K =-3/4ln(1-4/3p)
p = % difference (raw count)
Fig. 25.1
Saturation of DNA Sequences
Uncorrected genetic distance
Transversions
Transitions
Corrected genetic distance
http://www.ccg.unam.mx/~vinuesa/images/Ti_tv_saturation_plot.png
Lots of DNA substitution models to choose from:
Rates of nucleotide substitution between sequences:
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Rate = r = K/(2T)
*2T because substitutions accumulate simultaneously and
independently in both sequences (two lineages).
taxon 1
taxon 2
Rates of nucleotide substitution---factors affecting different rates:
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Different genes
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Coding regions vs. non-coding regions
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Codon positions
3rd pos.  synonymous substitution
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Synonymous rates ~5X > non-synonymous
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Substitution ≠ mutation
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Substitution implies that the mutation has passed through the
filter of selection.
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Synonymous substitutions are better approximations for the
background mutation rate
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Non-synonymous substitution ≠ mutation rate (more
influenced by purifying selection).
Nucleotide substitution rates differ within the gene in predictable ways:
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Most substitutions in 3’-flanking regions are tolerated.
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Rates: 3’ regions > introns > exons
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5’ regions < 3’ regions due to the presence of promoters and other
regulatory elements.
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Leader and trailer regions < 5’ regions; important for mRNA
processing and translation.
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Highest rates of substitution occur in non-functional:
pseudogenes & microsatellites
Wikipedia: Human pseudogene
Rates of evolution are different in mtDNA and chloroplasts:
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Organelle genomes (mtDNA, cpDNA) are distinct from nuclear
genomes and show increased rates of substitution.
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~10X greater than nuclear genes
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Possible explanations:
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Lack proofreading
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Different DNA repair mechanisms
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Higher levels of oxidative mutagens related to oxidative
phophorylation.
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Lower selective pressure; most cells contain several dozen if
not thousands of mitochondria.
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Maternally inherited; smaller effective population size;
increased effects of genetic drift and selective sweeps on
mtDNA/cpDNA variants that are beneficial.
Molecular clocks (fig. 25.3):
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Zuckerkandl and Pauling (1969): recognized that genes with similar
functions generally show uniform rates over long periods of time.
Biological causes of fast/slow molecular substitution rates:
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Substitution rates are expected to be related to germ line
replication (or generation time).
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Metabolic rate also is thought to be an important factor (correlates
with body size and generation time).
example: rodents are small, have a high metabolic rate, and have
short generation time/rodent rates are ~2x humans and apes.
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In addition to variation between and among genes, rates vary
widely among taxonomic groups.
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Other sources of variation:
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DNA repair mechanisms/efficiency
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Exposure to mutagens
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Opportunities to adapt to new environments, may lead to
bursts of rapid evolution.
Molecular clocks (cont.):
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Recognizing that “clocks” tick differently in different genes, these
can be used to estimate divergence time and compare rates among
lineages.
Relative rate test (Sarich and Wilson 1973):
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Measure # substitutions between two taxa and an outgroup taxon
that shares a common ancestor.
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doutgroup-1 > dooutgroup-2
taxon 1
outgroup
taxon 2
http://news.ucsc.edu/2014/12/crocodile-genomes.html
Three types of selection that occur on DNA sequences
Directional (positive) selection – natural selection favors one particular
genotypic variant or phenotype over others in one particular environment,
causing the allele frequency to shift.
Purifying (background) selection – removal of deleterious alleles (e.g.,
elimination of most non-synonymous substitutions)
Balancing (diversifying) selection – multiple alleles are selected for in the
gene pool and maintained at frequencies above the mutation rate
(Overdominance favoring the heterozygote is a type of balancing selection.
Diversifying selection in genes like MHC is the most extreme example).
Balancing/diversifying
Purifying/background
Positive/directional
http://en.wikipedia.org/wiki/Directional_selection
Michael Bamshad & Stephen P. Wooding - Nature Reviews Genetics 4, 99-111 (February 2003)
Example of directional/positive selection
Examples of balancing selection:
Light and dark-colored moths in the same population in England
Examples of balancing selection:
Major histocompatibility complex (MHC)
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Genes are important in immune response and are under selective pressure
to diversify (diversifying selection).
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~90% of humans receive different MHC genes from each parent.
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Sample of 200 humans will have 15-30 different alleles.
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Important mechanism for outcrossing in humans.
Humans select mates on the basis of their MHC compatibility.
http://www.genepartner.com/index.php/science
A common type of purifying/background selection is codon usage bias:
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Some synonymous codons are favored over others. In yeast Leu
codons: 6 possible codons/80% are UUG
Possible explanations:
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All involve selection.
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Some tRNAs may be more abundant or efficient; bonding energy
may differ due to differences in base pairs.
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Codon usage bias permits smaller # of tRNAs (e.g., Wobble effect).
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This type of selection is expected to be more intense for genes
expressed at higher levels/organisms with short generation times.
http://2014.igem.org/Team:Oxford/codon_optimisation
How to build trees - phylogenetic systematics-concepts/definitions:
Taxon
Monophyletic group of organisms recognizable by a set of shared
characters and sufficiently distinct from other such groups to be ranked
in a taxonomic category.
Category
Hierarchical level to which taxa are assigned in a classification (e.g.,
kingdom, phylum, class, order, etc.).
e.g., King (Kingdom) Phillip (Phylum) came (Class) over (Order) for
(Family) good (Genus) steak (Species).
How to build trees - phylogenetic systematics-concepts/definitions:
Monophyly
Descent from a common ancestor; every true taxon is monophyletic.
If we build a good phylogeny, our groupings are monophyletic.
Polyphyly
Descent from more than one ancestral lineage.
If we build a poor phylogeny, polyphyletic groupings will be created and
the phylogeny will need to be revised.
Wikipedia: Warm-blooded animals are polyphyletic
Phylogenetic Systematics-Important Definitions
Homology is good for building trees!
Shared similarity derived from common ancestry.
Homoplasy is bad for building trees!
Similarity derived from:
Convergence
Parallelism
Reversal
What causes Homoplasy?
Convergence
Independent acquisition of a similar character by two or more taxa
whose common ancestor lacked that character; generally refers to more
distantly related lineages. Ancestral lineages possessed different
character states.
Parallelism
Independent acquisition of the same or similar characters by more
closely related lineages (i.e., similar to convergence). Ancestral lineages
possessed the same character state.
Reversal
Reappearance of an ancestral character as the result of the loss of a
derived character.
Simplest phylogenetic trees:
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Branching patterns (trees) depict genealogical relationships
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Useful for molecular/non-molecular data
The 3-taxon example:
Fig. 25.5
The # possible phylogenetic trees grow by a factorial:
# of possible rooted trees
= (2n -3)!/(2n-2(n-2))!
# of possible unrooted trees
= (2n -5)!/(2n-3(n-3))!
# taxa
# rooted trees
3
3
4
15
5
105
6
945
7
10,395
8
135,135
9
2,027,025
10
34,459,425
For n = 20 there are 8.87 x 1023 possible trees.
Finding the “best” tree:
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Long tradition of using characters (morphological and molecular).
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Ernst Haeckel (1866)
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1950-1960s
Phenetics – computer algorithms
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Willi Hennig (1966)
Cladistics
Willi Hennig’s cladistic characters:
Synapomorphy: shared derived homologous characters
inferred to have been present in the nearest common ancestor
of two or more taxa, but not in earlier ancestors outside this
group (phylogenetically informative).
Symplesiomorphy: shared ancestral homologous characters
inferred to have been present in the nearest common ancestor
of two or more taxa, and in earlier ancestors outside this group
(phylogenetically non-informative).
Autapomorphy: unique derived character present in only one
of two sister groups (phylogenetically non-informative).
Synapomorphy
Synapomorphy
or
Symplesiomorphy
Autapomorphy
Tree reconstruction methods:
Genetic distance:
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Create a matrix of genetic distances describing genetic distances between all
pairs of taxa.
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Select the tree that minimizes total genetic distance (distances can be
weight or unweighted and may or may not conform to molecular clock).
Parsimony:
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Minimize number of steps required to evolve shared derived homologous
characters (synapomorphies) on the tree (characters may be weighted or
unweighted).
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Shortest tree is the best tree by principle of parsimony; i.e., the explanation
that requires the fewest assumptions is preferred to other more complex
explanations.
Maximum likelihood/Bayesian methods:
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Similar character based approaches but use ‘statistical’ methods such as
maximum likelihood and attempts to model DNA evolution as we know it
(assuming different frequencies of nucleotides, substitution rates, etc.).
Pairwise genetic distance matrix and a tree:
http://www.funpecrp.com.br/gmr/year2006/vol3-5/gmr0187_full_text.htm
How to count character changes using principle of parsimony:
taxon 1
taxon 2
outgroup
taxon 1
Most parsimonious
outgroup
Less parsimonious
taxon 2
Fig. 25.7, All possible trees depicting
nucleotide substitutions at six sites.
Fig. 25.8, Tree of life based
on 16s rRNA sequences
Fig. 25.2, mtDNA network showing lineage relationships in pocket gophers.
Problems with tree reconstruction methods (cont.):
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One or more (perhaps many) trees may best describe the data.
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Equally parsimonious/likely trees may not be consistent (character
support can be assed in different ways; e.g., bootstrap resampling).
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Gene trees and species trees: a gene tree does not necessarily
reflect the species tree.
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Common ancestor or two gene lineages
can predate species split:
ancestral polymorphism.
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Trees derived from different genes
or linkage groups may conflict and/or
or show very different patterns.
A
B
C
B
or
C
A
Peters, McCracken, et al. (unpubl. data)
Hybridization
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Gene flow between species or populations also may obscure the true
species tree and give you a different tree:
A
B
C
A
or
C
B
The other big problem:
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Recombination complicates phylogenetic inference by erasing
information and flattening the tree.
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But remember, different species don’t usually recombine!
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Problem for microevolution but not macroevolution.
Speciation and species concepts: Allopatric model
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If populations become subdivided, allele frequencies naturally
change over time and and populations diverge.
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Allele frequency differentiation measured using Wright’s Fst.
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If or when populations reunite, they may fail to mate or produce
inviable offspring  allopatric speciation.
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Or they might introgress and hybridize; the degree of speciation
depends on pre- and post-zygotic barriers.
Biological Species Concept
Systematics and the Origin of Species
Ernst Mayr (1942)
Allopatric Model
Peripatric Model
vicariance
Vicariance results in
subdivision and through
time leads to two
reproductively isolated
species clades evolving on
different trajectories .
Migration event followed by
peripheral isolation (founding
population persists; new
daughter species buds off).
Allopatric
Peripatric
Parapatric
Sympatric
Speciation: Sympatric/Allochronic models
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In some cases, speciation may be driven in the absence of
allopatry or peripheral isolation.
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Speciation and reproductive isolation can correlate with ecological
preferences (sympatric) or timing instead of space (allochronic or
heteropatric speciation).
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Examples of sympatric speciation are thought to be driven primarily
by adaptation as opposed to vicariance associated with geography.
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Several good examples of sympatric speciation documented:
Threespine stickleback
(Gasterosteus aculeatus)
http://fish.dnr.cornell.edu/nyfish/Gasterosteidae/sticklebackpic.html
Sticklebacks inhabit lakes and
streams in recently deglaciated
habitats, evolved from marine
ancestors.
Types of barriers to gene flow:
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Spatial, temporal, and ecological isolation
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Post-zygotic barriers
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Hybrid sterility/inviability
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Haldane’s rule: sterility and inviability occurs more often in
the heterogametic sex (e.g., because deleterious alleles are
exposed on the Y chromosome).
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Hybrid breakdown: inviability occurs some generations later.
Pre-zygotic barriers
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Behavioral incompatibility
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Mechanical isolation (genitalia do not fit together)
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Gametic isolation (gametes fail to fuse)
Reinforcement
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Pre-zygotic barriers evolve to reinforce post-zygotic barriers
Concluding remarks:
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No sharp division between phylogenetic systematics and population
genetics.
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Same forces that give rise to micro-evolutionary patterns we
observe are responsible for macro-evolutionary patterns that play
out over many generations.
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It’s all a continuum.
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Successful integrated analysis requires basic knowledge of
population genetics and phylogenetics.
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The toolkits that molecular evolutionists use are applicable to all
kinds of biomedical studies.
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Take my class next semester if you want to learn more.