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BIOL 4160 03 Variation
BIOL 4160
Evolution
Phil Ganter
301 Harned Hall
963-5782
Pollen newly released from the maturing flowers on this spathe
Genetic (and some Phenotypic) Variation
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Types of Gene Variation
Chromosomal and Genomic Variation
Mutation, Variation and Randomness
Recombination and Variation
Hardy-Weinberg
Variation Within Populations
Variation Between Populations
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Types of Gene Variation
Structure of Genetic Material
Gene Structure
Alleles are varieties of Genes found at a particular Locus in the Genome
But the term gene is used loosely by many
concept of gene has expanded and altered well beyond the one-gene, one protein hypothesis
Types of Genes
Protein Coding Genes
Coding Sequence and Exons
Alternative Splicing multiple exons can be combined in various ways to produce multiple proteins from one gene
Exon Shuffling - constructing new genes by combining exons from different loci
Introns (INTRagenic regiON - Walter Gilbert)
present in eukaryotic pre-mRNA (also called hnRNA - heterogeneous nuclear RNA)
Four classes
Self-Splicing Group I and Self-Splicing Group II Introns
both important in organelle genes and Group II important in rRNA (ribosomal RNA) processing, both are spontaneous
splicing, Type II requires guanine nucleoside as catalyst
Spliceosomal Introns and Enzymatically-spliced Introns
Spliceosome is a complex of proteins and RNAs, mechanism related to Group II self-splicing
Enzymatically spliced mechanism not like other splicing mechanisms
Enhancer Region(s) where Transcription Factors (both enhancers and repressors) bind to regulate RNA polymerase binding
can be a long way from rest of gene as intervening DNA can loop and bring enhancer site close to promoter
Promoter Site where RNA polymerase binds to DNA
Poly-Adenylation Addition Site
binds the cleavage complex (that cleaves the RNA) and polyadenylate polymerase (that adds up to 250 or so A's)
Mature mRNA is stabilized by 5'-GTP Cap and the 3' poly-A tail
Non-Coding RNA Genes (only a partial listing)
Ribosomal RNA (rRNA) Genes for RNA]'s found in ribosome
Cleaved from a single RNA molecule and the gene for this large molecule is Tandemly Repeated
Transfer RNA (tRNA) Genes for binding to Amino Acids
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Telomerase RNA - part of complex responsible for building telomeres
RNA Genes for RNAs involved in gene regulation
Antisense RNA (aRNA) Genes that bind to mRNAs
MicroRNA (miRNA) Genes
average only 19-25 bp, in eukaryotic cells only, and are post-transcriptional regulators that bind to complementary
sequences on mRNA
less than 100% complementarity so they can bind to multiple transcripts (gene silencing)
human genome has about 1000 miRNAs
Small Interfering RNA (siRNA) Genes that help regulate protein production in most eukaryotes through the RNA interference
(RNAi) pathway (21-22 bp)
100 % complementarity and so target specific genes
usually act by cleaving mRNA (gene silencing) and may be important immunity genes in organisms without cell-mediated
immunity (plants, non-mammal animals)
Long NC RNA Genes are regulatory but act in multiple ways
Several RNA species that seem to bind to invasive nucleic acids (piRNA against transposon activity is an example)
untranslated small RNA's
Genome Structure
Genomes are still being explored and much data is only preliminary
Bioinformatics is a series of mathematical tools and programs used in the exploration
Annotation is the process of identifying gene sequences
Genome size varies greatly
Prokaryote genomes usually less than 10 Mbp (mega base pairs or 1 million base pairs) but eukaryotic genome sizes can be over 100 billion
base pairs (100 Gbp)
Synteny is the order of the loci on chromosomes (actually means that the same loci should be found on homologous chromosomes)
Synteny is altered when translocations and duplications alter genes
Single Copy sequences
Single copy sequences include both Protein-Coding Genes and Non Protein-Coding Genes (some small amount of repetition may occur here)
Repetitive DNA sequences
rDNA Tandem Repeats (ITS = Internal Transcribed Spacer), multiple copies of tRNA genes
Microsatellites short repeated sequences (microsatellites = simple sequence repeats or SSRs) - 2-8 base pairs, tandem repeats (# of
repeats variable) used to map an allele
Autonomously Replicating Sequences (large diverse group, only some discussed here)
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Transposons
lots of them, some are DNA and some are RNA
Can cause mutations by inserting into a gene or a gene's control regions
Retrotransposons are most common and code for several proteins (including Reverse Transcriptase or RNA-dependent DNA
Polymerase)
LINES (long interspersed nuclear elements) repeated sequences up to 1000 to 5000 bp in length and up to millions of copies
Some have both Reverse Transcriptase and Integrase genes and can replicate like any other transposon and some have lost that
function and no longer replicate themselves
Differ from transposons in that they do not move from place to place in the genome but make copies of themselves and, when the
copies integrate, the genome size increases
Most copies lose functionality, so they do not copy themselves
Evidence for evolution of a balance between LINE expansion and the negative effect of so much unproductive DNA is scarce
There is evidence that some genes resulted from integration of a LINE (or a SINE) into a pre-existing gene, so LINES and
SINES may have a role in producing genes with novel functions
SINES (shorter than LINES) are less than 500 bp long and can occur in millions of copies in some genomes
SINES never code for RTase and so only spread in the genome when other transposons or LINES provide the means to do so
ALU elements most common repeat in humans - contain ALU-1 restriction enzyme site (hence the name) and were mutated from an RNA that
functions in the signal-recognition particle (part of the mechanism for targeting mRNAs to the endoplasmic reticulum)
ALU insertions are implicated in some human diseases
Latent Viruses
It's a continuum from virus' that never integrate and always have protein coats to latent viruses and virus-like sequences that
replicate
Gene families (based on protein families)
A set of related loci formed by local gene duplications
Usually have similar functions (LDH family, Hemoglobin family)
Pseudogenes are genes that have lost function through mutation
may be important in gains of novel functions as the can accumulate mutations while not functional and eventually mutate back to
functionality
many gene families have related pseudogenes (Hemoglobin family)
Mutations
Point / Indel Mutations and Third Codon Degeneracy
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(Transversion, Transitions, Synonymous and Non -Synonymous, Frame Shift, Sequence Termination by creation of Stop Codon)
INDEL (insertion or deletion) mutations often mean loss or alteration of function
Single-Nucleotide Polymorphisms (SNPs) are useful mapping markers and can label individuals
Neutral Mutations have no effect on the fitness of the organism
Synonymous nucleotide substitutions (usually 3rd position of the codon) are neutral because there is no alteration of the phenotype
If a mutation alters a protein, it may do so in such a way as to not alter the protein's function, so this would also be a neutral mutation
Neutrality is probably most common outcome
Deleterious Mutations decrease fitness
Pleiotropic effects - a gene that affects more than one phenotypic trait (eye color mutations of Drosophila exhibit pleiotropy)
Beneficial mutations occur at a low rate but this is expected in Darwin's gradualist view of evolution
Epistasis is when two or more loci interact in their effects on a phenotype
Recombination Mutations
Gene conversion using one allele to alter the other allele so that it is identical to the first (the second has been converted to the first)
happens during crossing-over and is caused by mismatch repair of incorrectly paired DNA strands
Intergenic Recombination - crossing-over of short sequences within a larger gene sequence
Unequal Crossing Over
causes one DNA strand to lose a section and the other to gain a section
the DNA strand that gained can then have a Gene Duplication
Most common where there already is a tandem repeat (misalignment of repeats)
Probably responsible for much of the amplification of LINES and SINES
Transposons and other repeated sequences can cause Rearrangements if paralogous copies align during synapsis
Forward and Back Mutations
These terms are "pre-sequencing" when all gene mutations were detected by changes in phenotype
Forward mutations are more common than back (many things can change an allele but only a very few specific changes will restore it)
Variation in gene structure vs variation in gene expression
variation in both leads to phenotypic variation
Mutation rate (usually point mutations)
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Estimated in lab experiment or by comparison of orthologs in different lineages (usually different species)
Need to reduce the chance that natural selection has altered the rate and measure just the changes caused by random error
Concentrate on pseudogenes, other untranscribed sequences, and four-fold degenerate sites
Key to this is to understand that:
Each substitution produces two alleles at that site
One is very common (wild type) and the other is represented by one copy in the population or species
The chance that mutation will become so common that it replaces the original allele is, if only random chance is involved, equal to the rate at
which mutations arise (more on the when we cover genetic drift)
So, if we count the number of replacements, we can estimate the mutation rate
There is a need to correct for the chance that, at any site that mutated, a second mutation occurred that changed it to another base or restored
the original base
Empirical measurements indicate that mutation rates vary among lineages, loci, and even within loci
Remember that time here is difficult to compare between different organisms
Different generation times mean that, for a given number of years, some lineages will have more opportunities to mutate (which happens when the
genomes are replicated
Only want to consider germ line cells, not somatic cells
That said, the variation in rate (per base pair per replication) is not so large (probably due to similarity to replication process in all organisms)
chance of mutating is about 0.3 x 10-10 to 6 x 10-10 per base pairs per replication
If we assume a rate of 3 x 10-10 for our genome, then each time we replicate it (7 x 109 base pairs in our diploid genome), there is only a 1 in 5 chance
of getting any changes at all
But, from the zygote to the egg or sperm, there is at least 100 replications, and so we can expect at least 20 mutation in each gamete
Mutagens are chemicals that alter the chance of mutations (always increase the chance), which is why we try to restrict releasing some chemicals into our
environment
Chromosomal Variation
Ploidy Changes
Aneuploidy, Polyploidy (Allopolyploidy, Autopolyploidy)
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Inversions
Translocations
Fission and Fusion
Karyotype Variation
Figure 1 - Karyotypes of 36 strains of an asexual yeast, Candida sonorensis, showing the sorts of extreme karyotype variation found with asexual "species."
It is often hard to be sure that a yeast is truly asexual but it is hard to see how synapsis during meiosis could be achieved between some of the strains of
this yeast. There are no known phenotypic differences between the strains listed below. This raises two related questions. First, are we missing important
parts of the phenotype? If not, where did the extra DNA in the larger genomes come from and what does it do?
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Mutation, Variation, and Randomness
Variation is ultimately the outcome of mutation
Mutation is a random process
Thus, mutations do not happen when the will help an organism -there is no "directed mutation"
However, development (and other constraints) may mean that not all conceivable phenotypes are possible
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Recent challenges to this assertion have been shown to be wrong and have reinforced the assumption of randomness in mutations
Mutation rate is not a random effect
Different lineages have different rates of synonymous mutation
Different regions of the genome have different mutation rates
Environmental conditions can alter mutation rate
Although mutations are random, variation is the outcome of many mutations and is predictable!
Natural selection, in cases where there is a single allele or combination of alleles, genetic drift, and inbreeding will work to reduce variation in a population,
which can only be replenished by migration of new alleles or mutation
Problem: When lab populations of animals are subject to artificial selection, the most common response it that the character being selected
changes in the direction encouraged by selection. So, one can reduce the number of facets (individual visual cells) in the eye of a Drosophila by
selecting for this by only allowing flies with the fewest facets to contribute eggs to the next generation. Wim Scharloo did a laboratory
selection experiment with a population of 1000 flies. After several generations of selection during which the character selected changed, change
stopped. Prof. Scharloo then made one change in the experiment. He increased the population size from 1,000 to 10,000. Selection almost
immediately became effective again and the character continued to change. Why did the expansion of the population restart the evolutionary
process?
Mutation and Fitness
Neutral mutations are those that do not affect fitness (no matter why)
Pleiotropy
when the output from a particular locus affects more than one character, the gene's effects are said to be pleiotropic
a mutation's effect must be assessed for all characters affected by that locus as the mutation's effects may differ by character affected
For those mutations that increase or decrease fitness, remember that fitness is not the property of an allele, but the outcome of an allele in a particular
environment (both physical and biological environment)
A mutation that alters coloration of prey is only as important as the risk of being eaten
It is assumed that it is easier to harm a complex machine by randomly changing its parts than to improve it by random change (mutation), so harmful mutations
are expected to be more common than beneficial mutations
Text example of bacterial evolution in which 1 in 150 mutations were beneficial (and the average fitness increase was 3% is surprising for how many
beneficial mutations occurred and for how beneficial they were
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Phenotypic Variation
This is an extensive subject and all we will do here is to point out some basic relationships between genetic variation and phenotypic variation
Phenotypic variation is the degree of differences between the physical characteristics of related organisms
Sources of Phenotypic Variation
Genetic Variation - discussed previously
Environmental Variation - differences among individuals due to the influence of their environment (including their biotic environment)
Usually measured by measuring phenotypic differences when the genotype is held constant
Developmental Noise - the differences in individuals of the same genotype raised under identical environmental conditions
Maternal Effects - these are differences caused by non-genetic influence of the mother on her offspring
Variation among ova (not DNA, but differences in the stocking of the egg with energy and food resources, specific proteins and RNAs
Variation in mother's condition when producing eggs or carrying offspring
Variation in maternal care (this can be due to father as well)
Epigenetic Inheritance - differences in genetic expression of a locus not based on sequence differences among alleles
Liver cells, in culture, undergo mitosis but produce only liver cells - they do not revert to zygote or stem cell status
Genetic imprinting - dealt with in Evo-Devo chapter
Describing Phenotypic Variation - the measure used is Variance (from statistics) in a character, which is a measure of the deviation of individuals from the
mean character value (assumes one can use numbers to measure the character)
At the simplest level, the variance in a trait within a population or species can be divided into two additive portions:
Phenotypic Variation (Vp) = Genetic Variation (VG) + Environmental Variation(VE)
Phenotypic plasticity - a single genotype often can produce more than one phenotype if the environment in which the organism develops changes - this
is the Reaction Norm of that genotype (all possible phenotypes from a single genotype)
In this case (which may be the usual case), then we must alter the partitioning of phenotypic variance:
Phenotypic Variation (Vp) = (VG) + (VE) + Genotype x Environment Interaction (VGxE)
Recombination and Variation
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Parasexual recombination (conjugation, transduction, transformation)
Horizontal versus Vertical Transmission
Recombination at the molecular level
Homologous and Non-homologous
Sexual recombination
combinations of genes are not preserved unless the genes are closely linked (no linkage is ever tight enough to completely prevent recombination)
Recombination can be intergenic
Recombination produces new combinations of genes each generation
To preserve favorable combination of genes, some other process must operate (positive assortative mating is one possibility)
Linkage
Physical linkage means that the loci are close enough on a chromosome that they are likely to be inherited together
If two loci each have two alleles in a population and the proportion of each allele is 0.50, then unlinked genes should be in Linkage Equilibrium
in this case, 25% AB, 25% Ab, 25% aB, and 25% ab,
Linkage Disequilibrium is a significant departure from the proportions expected from linkage equilibrium
In the case above, if Ab is one chromosomal type in the population and aB is the other (and no recombination occurs because the linkage is so
tight) you get 50% Ab, and 50% aB (no recombinant allele parings [AB or ab] are formed)
Linkage disequilibrium, then, is a measure of the inhibition of recombination and indicates some evolutionary process may be affecting the
outcome of recombination (assortative mating, selection, etc.) in addition to simple physical linkage
Hitchhiking - when one allele is changing frequencies due to selection (for or against), neighboring alleles may also change if closely linked
Hardy-Weinberg
Variation is a population-level phenomenon (emergent property of populations) and a necessary condition for evolution
What should we expect to happen over time when variation exists in a population?
Hardy-Weinberg expectations are predictions of future population variation when that variation is not altered by ecological or statistical
processes
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p2 + 2pq + q2
H-W Assumptions - Hardy-Weinberg predicts no change but is only accurate if its 5 assumptions are met. Below we list the assumptions and discuss what
happens when the assumption is violated.
No mutation,
Mutations generate differences between generations and upset H-W prediction
No migration,
If populations differ in their genetic composition (maybe A is 90% of the genes at a locus in one population and only 10% in another population),
migration between the populations can change their genetic composition
Random Mating,
Assortative mating (also called Non-Random Mating)
Positive Assortative Mating - if like mates with like (due to choice or to small population sized not allowing much choice) then intermediates
and heterozygotes are lost - a decrease in genetic variation
Negative Assortative Mating - like mating with unlike will increase the proportion of heterozygous intervals and preserve genetic variation
Inbreeding
has the same effect as positive assortative mating - loss of genetic variation
two related individuals are more likely to have a rare allele, given that one of them does, than two individuals chosen at random from
the entire population, thus rare recessive alleles are more likely to become homozygous in inbred offspring
can (not must, but can) lead to lower viability of inbred individuals or to lower fecundity
Heterosis - condition where the heterozygous individuals show greater fitness (viability, fecundity) than do individuals homozygous for
either of the alleles
Inbreeding Depression - loss of fitness due to inbreeding as more and more recessive, less fit alleles are expressed due to inbreeding
more likely in small populations
often there are physical or behavioral barriers to inbreeding
Large Populations,
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Genetic Drift
loss of genetic variation due to chance events
more likely in small populations than in large
Neighborhoods can enhance the effect of drift
if populations are subdivided into small neighborhoods, then drift will be more important for the entire population
Bottleneck - a sudden low point in populations numbers, followed by expansion of the population
Bottlenecks can reduce genetic variation in a generation through genetic drift, even though population numbers are generally high
If you come along when the population has recovered its large size, you would think that genetic drift was not important in that
population, but a recent bottleneck event might have greatly reduced genetic variation in your study population.
Founder Effect
if new populations are formed by the migration of just a very few individuals, the population can be said to have gone through a
bottleneck at its founding
founder effect can mean that new populations are different from parent populations through chance alone
No Selection
Natural selection is the outcome of fitness differences between individuals
Natural selection requires that there is heritable genetic variation in a population
if some of those genetic variants are more fit (better able to survive and reproduce) than others, the fit genetic variants will leave more
offspring that also have their "fit" genotypes
as time goes on, more of the population are descended from the more fit individuals
An example - Peppered Moth melanic forms favored when trees are darkened, light form when trees are lighter
selective factor is mortality due to bird predation
melanic gene has other effects, but none are strong enough to explain the population changes seen in England
in the US, melanic form has declined even though trees are not becoming lichen covered, so NS by bird predation may not work for all
cases of Industrial Melanism
Prevalence of resistance to herbicides, insecticides, rat poisons, and antibiotics are also examples of natural selection
Natural Selection can enhance, reduce, or maintain variability
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Natural selection can, under the right conditions, favor polymorphism (two or more alleles or phenotypes in a population) can result in a Balanced
Polymorphism if each phenotype has an environment in which it is most fit form
Cepaea snail's (a large land snail) shell banding varies with the background and can hide the snail from bird predation
populations are made up of different forms, each form with an environment in which it is the fittest
natural selection favors more than one phenotype within a single population here
Natural selection can have different effects on a population, which we have divided into three "modes of selection."
Disruptive (Diversifying)
when the extremes are fittest and intermediates are less fit
Can split a population into two phenotypes with few intermediate forms
Stabilizing
when the fittest individuals are the average, then those with more extreme (larger and smaller) phenotypes are less fit and NS will act
to reduce the number of individuals with extreme phenotypes
Directional
when a new, fitter type originates, the population will move from the older type to the newer type over time
Natural Selection produces Adaptations
Adaptations are those characteristics of organisms that allow one organisms to be more fit than another
Populations adapt to environments as natural selection increases the proportion of individuals that have the most fit adaptation
All three modes of selection (disruptive, directional, and stabilizing) will produce adaptation (in the case of disruptive, more than one adaptation).
Variation Within Populations
Are all differences among individuals in a population heritable genetic variation?
Phenotypic Variation (Vp) = Environmental (VE) + Genetic (VG)
Genes may have different effects when in different environments
many genes are expressed differently when temperature differs
expression of many genes depends on genetic environment - what alleles are present at other loci - dominance is a good example of this
effect
Therefore, we must added a term for gene-by-environment interactions (VG+E)
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Phenotypic Variation (Vp) = Environmental (VE) + Genetic (VG) + Interaction (VG+E)
Heritability
Proportion of phenotypic variation that is due to genetic variation
h2 = VG / (VG + VE)
Note that the interaction term is not used and, if significant, makes heritability harder to measure and discuss
Often estimated through the slope of the line describing the relationship between the measure of a character in offspring versus the mean of the
parents (Midparent Mean)
Reaction Norms
A reaction norm is the change in phenotype produced by a single genotype in different environments
This is a way to quantify Gene x Environment interaction
often a scattergram with the phenotypic measure as the y-axis and the different environments (or range if the differences are continuous, like
temperature differences) on the x-axis
each genotype gets its own line and interactions are revealed when lines are not parallel
Variation Between Populations
We have already discussed the geographic relationship among populations (allopatry, peripatry, parapatry - no sympatry for populations of the same
species!!) when discussing speciation
Subspecies = Geographic Race
Clines form between extremes of populations or between parapatric populations
Adaptive Geographic Variation and Gene Flow
1. AGV adapts a local population to its specific, local habitat
2. Gene Flow counteracts AGV by homogenizing gene frequencies in a population or between local populations
Countergradient Variation
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a plant found in both harsh and benign environment grows slowly in harsh environment and quickly in benign environment
experiment - grow seeds from both populations in the benign environment
seeds from population in harsh environment grown faster than seeds from population in the benign environment
Environmental variation causes a gradient in growth rate
Genetic variation produces a counter-gradient in growth rates due to natural selection for faster growing plants in harsh environment
But, since the environmental effect is larger, one observes that plant grown more slowly in harsh environment (difference would be even greater
without the genetic countergradient)
Character Displacement
Variation among populations of a species as a result of some populations being sympatric with a related competitor species (or within populations
in which gene flow is limited by distance and part of the population is sympatric and part is not)
Character is displaced (=altered) by the effect of competition with the related species for resource, not by a change in overall resource
availability
(see book for examples)
F-statistics
Variation among individuals in a species can be subdivided into within-population and between-population components
FST is a measure of the proportion of variation among individuals at a locus due to differences between populations and it ranges from 0 (no difference
in allele frequencies) to 1 (different alleles fixed in each population)
There are several ways to calculate and/or estimate this and we will examine one here based on a locus with two alleles only (in all populations)
To calculate this, it is necessary to know the frequency of the alleles in each population, from which you can calculate the mean (q-bar) and variation in
q (VAR).
This equation will be 0 if there is no variation among populations (numerator = 0) and 1 when that variation is as large as the product of the average
frequencies of the two alleles (1 - q is the frequency of the other allele when only two are present)
Last updated March 1, 2011
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