Evolution
Wolf - Lecture 0 - Introduction
The process of organismal change and diversification through generational time from shared common ancestry
evolution (change) ≠ natural selection (process) ≠ adaptation (result of natural selection) ≠ speciation
is a trans-generational process
not accidental or random process, but it does not progress towards a goal
macro evolution vs micro evolution
macro evolution ist zwischenartlich und micro evolution ist innerhalb einer Art
macro evolution aus Anagenesis und Cladogenesis
micro evolution can result in complex structure
Anagenesis
Evolutionary change without multiplication of forms. Gradual evolution. Keine Artneubildung. Gradual evolution of a species that continues to exist as an interpreeeding population (chronospecies)
Cladogenesis
evolutionary splitting of a parent species into two distinct species, forming a clade (speciation)
Evidence for Evolution
Hierarchical organization of life
Homology (vertebrate extremities, orthologue genes)
Embryological similarities
Vestigial characters
Convergence
suboptimal design
Geographic distributions
fossil record
LUCA
Last universal common ancestor
Plato
the world is a shadow of underlying essences
Aristoteles
Scala naturae
species fixed, aligned in ladder of life
Kimura
The Neutral Theory of Molecular Evolution: “The great majority of evolutionary changes at the molecular level are caused not by Darwinian selection, but by random drift of selectively neutral or nearly neutral variants”
Ohta
The Nearly Neutral Theory of Molecular Evolution: allows for slightly disadvantageous mutations; Domponents of genetic diversity depend on population size
central dogma
Originally evolution was observed at the phenotypic level. Phenotype is determined by the genotype encoded in the DNA polymer interacting with the cell and the environment. Ultimately genetic variation is the raw material for evolution.
Evolutionary Processes:
mutation (generating variation)
selection (filtering variation)
migration ( moving variation between population)
recombination (shuffling variation within an individual)
genetif drift (modifying variation by stochastic processes)
Wolf - Lecture 1 - Mutation
Germline mutation
A gene change in a body’s reproductive cell (egg / sperm) that becomes incorporated into the DNA of every cell in the body of the offspring.
Germline mutations are passed on from parents to offspring
Somatic mutation
An alteration in DNA that occurrs after conception. They can occurr in any of the cells of the body except the germ cells (egg / sperm) and therefore are not passed on to children. These alteration can (but do not always) cause cancer and other diseases.
Example: Mosaicism
Careful: Somatic variation can also be due to epigenetic change (X-chromosome inactivation)
Mutation
the ultimate source of organismal variation
A process that produces a novel allele different from existing version(s) (or the wild type)
The allele that results from a mutational process
Mutant
organism or cell who has recovered a mutation
often also: whose changed phenotype is attributed to a mutation
Locus
an operational definition of a specific position in the genome and can refer to a single base pair, a stretch of sequence or a specific gene
Allele
Different character states of the locus
Either dominant, co-dominant or recessive
Haploid organisms
have only one copy of each locus and are limited to one allele (1n)
Diploid organisms
inherit one maternal and one paternal copy and can thus carry a total of two alleles at a single locus
Genotype
Combination of alleles
heterozygous individuals have two different alleles (e.g. Aa)
homozygous individuals have two copies of the same allele (e.g. AA, aa)
in diploids (and n-ploids in general) mutations always first appear in a heterzygous state
Haplotype
combination of alleles that are inherited together from a single parent
Haplotypes can have many more alleles than single polymorphic loci
Co-inherited allelic combinations of more than one locus
Diplotype
a specific set of haplotype combinations in a diploid
Polymorphism
Occurence of several allelic states
Homoplasy
describes a feature has been gained or lost independently in seperate lineages over the course of evolution
Mosaicism
two or more populations of cells with different genotypes are present in a single individual
Ploidy
change in the number of whole sets of chromosomes (aneuploidy, e.g. Trisomy-21 in humans) or even all chromosomes of a genome (poly-ploidization in maize)
Zygosity
the degree to which both copies of a chromosome or gene have the same genetic sequence
the degree of similarity of the alleles in an organism
homozygous, heterozygous, hemizygous (if one allele is missing), multizygous (if both alleles are missing)
phenotypic plasticity
component of the phenotype that is not environmentally determined
encoded in the DNA sequence
multigenic / monogenic
Traits can be encoded by many genes (poly / multigenic trait) or by a single gene (monogenic trait)
Gene mutations:
point mutations: mutation of one base into another
synonymous substitutions: do not alter amino acid sequences and are (sometimes) silent mutations; 3rd base pair of a codon usually a synonymous site
non-synonymous substitutions: nucleotide mutation that alters the amino acids sequence of a protein; 1st and 2nd sites usually non-synonymous
silent mutation: do not affect amino acid sequence of a protein
missense mutation: mutations that change a single amino acid
nonsense mutation: mutation resulting in a premature stop codon
frameshift mutations: insertion or deletion of a single base pair or short strech of nucleotides that shifts the tripet’s reading frame. Always results in a drastically different polypeptide product often introducing stop codons. The gene product is usually non-functional
Chromosomal / Structural mutations:
Insertions / Deletions
Duplications (generate paralogs)
Inversions
Translocations (exchange of segments among non-homologous chromosomes)
Fissions and Fussions (one chromosome becomes two or two become one)
Ploidy changes (change in chromosome numbers)
Karyotype changes
infinite sites model
the model makes the simplifying assumptions that (1) there are infinite number of sites where mutations can occur, and that (2) every new mutation occurs at a novel site
under natural conditions and depending on the organism the mutation rate is generally low enough that a locus / site is only affected once by a mutation until it has reached fixation
Measuring mutation rate - methods
Pedigree-based
Experimaental evolution
Comparative genetics (only for selectively neutral sites)
male-biased mutation rate
there are a larger number of cell divisions involved in the male sperm line than in the female germ line, more new mutations are transmitted through sperm than through eggs.
in male heterogametic species (male : XY) this has the consequence that the X-chromosome is exposed to fewer mutations than the autosomes, in female heterogametic species (female : WZ) it has the opposite effect
Null Model
Wolf - Lecture 2 - HWE
infinite population size
no random genetic drift
no selection
no mating preferences
no inbreeding
no mutation
no migration
no recombination
-> impact only of Medelian inheritance
random mating
non-overlapping generations
Deviations (Abweichungen) from HWE
Assortative mating: Individuals may be more likely to mate with individuals from the same / similar genotype
full assortative mating: AA / Aa / aa only mating with themselves
-> Heteozygotes will be depleted
Inbreeding:
same as assortative mating: if these matings are more common than expected under random mating, homozygote genotypes will rise in frequency and heterozygotes will become depleted
-> Inbreeding affects the whole genome, assortative mating only affects those loci that determine the trait relevant for mating preference. Given enough recombination, assortative mating diesn not affect loci elsewhere in the genome.
Population structure: Inadverently pooling individuals from two populations can lead to strong deviations from HWE
Selection: differential fitness (survival, mating success,…) among individuals due to their phenotypes
(Mutation and Genetic Drift)
Hardy-Weinberg-Equilibrium
man geht von einer idealen Population aus (Null Model)
Für diesen Fall ergibt sich für jede beliebige Genotypverteilung der Elterngeneration eine nur von den Allelfrequenzen abhängige Genotypverteilung der ersten Tochtergeneration, die sich in den folgenden Generationen nicht mehr ändert.
genotype frequencies stay constant or if they are totally out of Hardy Weinberg proporition in the first generation they will adhere in the next generation and correspond to those frequencies
Once HWE is reached, also the genotype frequencies do not change any further
at equilibrium, allele frequencies stop changing
Heterozygotes are the most common genotype in the population if the allele frequencies are between 1/3 and 2/3
processes that could potentially change genotype and / or allele frequencies in a population:
mutation
selection
segregation
recombination
genetic drift
migration
Genetic Drift
Wolf - Lecture 3 - Genetic Drift
process of random change of allele frequencies in finite populations
assumption: genetic variants under consideration are neutral and no selection (neutrality assumption = null-model of evolution)
Wright-Fisher Model
used to construct null hypothesis for the change of allele frequencies in populations. These hypothesis are then tested against data
Rejection of the simple Writh-Fisher model is then taken as evidence that something more interesting than “just mutation and drift” acts in the population, e.g. selection
assumes haploid (or diploid) population without sexes, in which each individual reproduces without the need of finding a mate
finite population size
discrete generations
random transmission to the next generation with equal probability
1) Allele frequencies changed within populations
some will not reproduce, some will have multiple offspring -> allele frequencies will fluctuate and eventually one of the two alleles get fixed and the other one lost
trace back: all individuals come from common ancestor
2) Variation in allele frequency increased across populations, mean stays the same
Genetic diversity within population gets lost
the colonies will diverge only very slowly if the population size is large
3) The probability of fixation and the time it takes
in absence of mutation, any allele must eventually be lost or fixed
the average amount of time it will take for a single allele to fix within a population is given by twice the number of alleles within a population. Hence, in a population of haploid individuals it will take 2N, for diploids 4N generations
4) Genetic drift erodes genetic variation
genetic variance within a population decreases
drift is mostly potent in small populations, in large populations it erodes genetic variation only very slowly
-> under simplifying assumptions the model could predict the state of a population in the next generation
Heterozygosity
probability of finding two different alleles at two homologous loci
Homozygosity
probability that alleles at two randomly drawn gene copy are equal
Factors contributing to HFC
Wolf - Lecture 4 - Neutral Theory
Effective population size (Ne)
Ne: reflects the size of an ideal population that experiences genetic drift at the rate of the population in question
Ne is defined by the quantity of interest as e.g. the inbreeding effective size, the coalescent effective size,…
sex ratio differences (Sexual selection); fluctuations in population size; overlapping generations; population structure -> reduce number of individuals contributing to the next generation
the relevant effective population size is often much smaller than the actual number of individuals, or census population size Nc
in an ideal population genetics drift will proceed at a rate given directly by the census population Nc
matters and appropriately describes the effect of genetic drift (such as reduction in heterozygosity, increase in variance in allele frequencies)
Neutral theory of Evolution (Kimura)
most changes at the molecular level resulted from a combination of mutation and genetic drift, without the ection of selection. In his theory selection is appreciated only in the form of strong purifying selection efficiently removing highly deleterious mutations such that they do not contribute to segregating genetic variation. Positively selected mutations play only a minor role. They are assumed to rapidly reach fixation, and hence do not contribute to segregating variation
the model:
most mutations are selectively neutral
some are under strong purifying selection
very few are under string positive selection
Markov Model
a stochastic model that describes changing systems where the next state is only dependent on the current state and is independent of anything in the past
Markov chain: simplest Markov model
In each generation we have a state (which we can observe) and that state changes in the next generation according to a known function specifying the transition probabilities
mutation-drift equilibrium
Genetic drift reduces heterozygosity within a population. Mutation will work against that reduction by increasing genetic variation. Therefore, at some point an equilibrium will be reached where the decrease in H due to drift is balanced by the increase due to mutation
infinite alleles model
assume that every new mutation results in a new allele not present in the population before
then every pair of genes with unequal alleles befor emutation will also have unequal alleels after mutation
every pair with equal alleles before mutation will become heterozygote if either of the genes mutates
-> equilibrium heterozygosity increases with increasing mutation rate and increasing population size
k (neutral rate of substitution)
k = neutral rate of substitution, defined as the number of all mutations that arise in the population times the probability that any of those mutations is fixed
k = 2μt
implies that molecular evolution at a neutral site occurs at an approximately constant rate per unit time -> shows molecular clock -> number of substitutions between two species can be used to infer the time since these species split from their common ancestor
identical by descent
two or more offspring share the same parent
Coalescent theory
Wolf - Lecture 5 - Coalescent Theory
approach describing a stochastical process of random reproduction backwards in time
selectively neutral mutations will not affect reproductive success: the neutral mutational process can be separated from the genealogical process (“state” can be separated from “descent”)
coalescence
that any two gene copies are derived from the same parnetal copy
(gene copies! -> that do not recombine over this time)
in finite population it is 1/N (Wright)
time to the most recenct common ancestor (TMRCA)
the sum of all waiting times Tk until the last two lineages coalesce (k = gene copies)
Time continuous coalescent
for large populations N that in a sample of k the waiting time until the first coalescence event is exponentially distributed with rate: (k over 2)1/N
in a growing population the external branches are long relative to the standard coalescent. As we move further back in time, the coalescence time is accelerated leading to short internal branches
Mutations and phylogeny tree
we expect more mutation on the long branches and fewer on the short branches
the construction of a genealogy is independent of the mutational process (separation of state and descent). Therefore we can simply add mutations onto the genealogy arising from the coalescence process.
Population Structure
we need to consider geographic structure: geographically close individuals are simply more likely to mate with each other
population structure is a disturbance that needs to be considered when we aim to infer selection or demographic processes
Wolf - Lecture 6 - Population Structure
What is a population?
population identity is inferred from morphological characteristics or by borad-scale geographic factors
2 approaches:
PCA
PC1: splits species, axis that explains the greatest possible variance in the data among all possible axes
PC2: splits population in species
Assignment methods
calculate the likelihood for each popualtion for the genotype of the samples individual
e.g.
pop 1 has allele frequencies fA = 1 and fa = 0
pop 2 has allele frequencies fA = 0.5 and fa = 0.5
consider individual with genotype Aa. The probability of it coming from pop 1 is 2*1*0 and from pop 2 is 2*0.5*0.5 = 0.125 thus we would conclude it belongs to pop 2
requires knowledge on population structure and the respective allele frequencies a priori
Natural Selection
Wolf - Lecture 7 - Selection
naturally occuring variation in average reproductive success among phenotypes (e.g. mating success, fertility)
variation in the phenotype, must be correlated to reproductive success
Selection happens irrespective of the nature of variation, but evolution by natural selection can only occur if variation is heritable
Natural selection ≠ evolution
Fitness
≈ reproductive success
survival, ability to attract / control / fertilize
Selection
≈ differential fitness
Selection is due to fitness differences of heritable phenotypes
Types of Selection
1) Directional: Selection causing a consistent directional change in the form of a population through time (e.g. selection for larger body size)
2) Stabilizing: Selection tending to keep the form of a population constant
3) Disruptive: Selection favouring forms that deviate in either direction from the population average
Selection does not necessarily lead to evolution. Evolution will only result if (1) variation in fitness is correlated with variation in the trait of question, (2) selection is directional and disruptive and (3) other forces such as genetic drift do not override the effects of selection -> still there is evidence that selection plays a large role in phenotypic evolution
Artificial selection (domestication)
Individual Selection
selection on phenotypes (or associated genotypes) that affect the fitness of the individual
segregation distortion
when allels manage to get into more than 50% of the offspring
meiotic drive
genes drive meiosis into a biased outcome
if transmission of the selfish genetic element is controlled by female meiosis or genic drive if associated with male gametes (e.g. through sperm competition)
rareness of it suggests that it is difficult for single genes to win out a competition against the organism - and all other genes - in the long run
Adaptation
the end product of natural selection: A trait that enables an individual to leave more progeny is called an adaptation
3 kinds of traits:
traits that are beneficial: true adaptations
traits that are neutral
traits that are deleterious
Crysis (hide)
Mimicry (imitate)
Batesian mimicry
The palatable species is protected by resemblance to unparatable or dangerous species
a form of paratism
Müllerian mimicry
multiple unrelated unpalatable species resemble each other
advantageous for all models; there is thus coevolution to a common phenotype
Nearly neutral theory
claims that molecular differences are mostly due to nearly neutral mutations. Assuming a fixed distribution of selection coefficients (distribution of fitness effects) the proportion of nearly neutral mutations decreases with increasing population size.
As a consequence, the nearly neutral theory predicts a weaker dependence of the heterozygosity than the original neutral theory. This fits better to the observed data. E.g. we observe much less heterozygosity in species with large Ne.
Lewontin’s paradox
There are many examples of species whose Ne values, as indicated by their levels of DNA sequence variability, are several orders of magnitude smaller than the estimated numbers of adult individuals, especially among invertebrates and even more so in microbes.
The fact that levels of DNA sequence variability differ among species far less than would be expected from differences in their population sizes
Role of drift in adaptation: Wright vs. Fisher
concept of adaptive landscape: with peaks and valleys
Scenario Wright:
Adaptation is a multi-step process that follows from the interplay of three basic evolutionary forces: drift, selection, migration.
efficient selection cannot be by (mutation and) selection alone. Solution: Shifting balance theory.
Evolution to a new adaptive peak is a 3 step process:
Drift: Just by chance, one of many medium-sized subpopulations may drift off the historical fitness peak
Individual Selection: natural selection then sweeps this subpopulation to some new and higher optimum
Migration: migrants from the better adapted subpopulation spread the adaptation to the entire population
Scenario Fisher:
Adaptation is a simple hill-climbing process that is driven by selection as the allmighty force. This is the classical adaptationist view.
Shifting Balance does not work: because it needs a subtle balance of evolutionary forces that is unlikely to be widespread
Other solutions to the problem (Fisher?):
multiple fitness peaks only exist if there are non-additive gene effects (epistasis)
the analogy at the walk on the 2D surface max be misleading: for most traits there are not only 2 loci, but many
adaptive landscapes are not rigid objects, but should be thought of as variable as environmental conditions change
Most evolutionists today do not believe that shifting balance is necessary (or likely) for adaptation on the trait level, which are influenced by many genes. At this level, selection is thought to be often stronger and interactions among genes less likely to create local peaks.
Merill - Lecture 1 - Recombination
Specific, fixed position in the genome
alternative character states of the locus (often denotes A, B, a, b, etc.)
Combination of alleles of an individual which determines the phenotype
Phenotype
the physical expression of the genotype
Mendel’s law of segregation
Allele pairs separate (segregate) during gamete formation, then randomly unite at fertilization
Mendel’s law of independent assortment
Alleles at two (or more) different loci are sorted into gametes independently of one another
Mendel’s laws
Law of segregation
Law of independent assortment
Law of dominance
test cross
breeding an individual with a phenotypically recessive individual
if mother heterozygous: YyRr x yyrr = YRyr, Yryr, yRyr, yryr
-> offspring phenotypes in equal frequencies (1:1:1:1)
if mother homozygous: YYRR x yyrr = YyRr -> all offspring are the same
Pleiotropy
different traits are controlled by the same alleles (act like a single trait)
Linkage
if loci influencing different traits are near on the chromosome
In case of linkage on the same chromosome, no recombinant genotypes would be expected
Example: intercross F0: RRYY x rryy -> F1: RrYy
Gametes without linkage: RY Ry rY ry
Gametes with linkage: RY ry
Gene mapping
describes the methods used to identify the locus of a gene and the distances between genes. Gene mapping can also describe the distances between different sites within a gene.
with different phenotypes, proportion of recombinants range between 0 (no recombination) and 1 (full recombination) providing clear evidence for crossing-over in the female germline
today genetic maps do no longer require phenotypic assays -> can be directly constructed from genotypic markers using informative crosses / pedigree data from natural populations or single sperm sequencing
centimorgan (cM)
1cM = 1 recombination in 100 offspring
unit of recombination frequency
multiples of 0.01 (1%)
Recombination
Recombination frequencies differ between species and sexes, but also differ significantly among chromosomes within species
recombination rate tends to be elevated in small chromosomes
Recombination also varies along the genome, often with strongly reduced recombination in regions of dense heterochromatin (e.g. around centromere)
Recombination is a central parameter for many aspects of evolution
Recombination generates phenotypic diversity (e.g. height, not either or but different heights)
In case of linkage one has to wait longer, but eventually recombination will unlink loci and introduce novel combinations
number of gametes generated by recombination: 2^n gametes from n loci
number of genotypes generated by recombination: 2^n-1 (2^n + 1)
Recombination speeds up adaptation:
with recombination favourable mutations at different loci can be combined
if there are two favourable mutations at different loci, they compete and the haplotype with the mutation conferring less of a selective advantage will eventually be lost from the population
in a sexual population with recombination, they combine and so both advantageous mutations survive
With recombination selection will thus act on the locus, without recombination it will act on the entire haplotype
Recombination counters the accumulation of deleterious mutations
individuals free of mutation = individuals with fittest genotype -> will eventually be lost by genetic drift and can never be recovered -> decreasing the fitness of the entire population. Unless there is backmutation or recombination recreating mutation-free haplotypes the expectation in the long run is that the population will go extinct
Hill-Robertson interference
if an advantageous mutation happens to end up in a haplotype with deleterious mutations, it will not reach fixation
Linkage Disequilibrium
correspondence or non-random association of alleles at two or more loci / at different loci within a population
Loci are said to be in linkage disequilibrium when the frequency of association of their different alleles is higher or lower than what would be expected if the loci were independent and associated randomly
depends on multiple factors like local recombination rate, non-random mating, mutation rate, genetic drift, population structure
Linkage Disequilibrium ≠ physical linkage (but physical linkage of loci can lead to linkage disequilibrium) -> contrary to linkage due to a physical connection of neighboring loci on the same chromosome, Linkage Disequilibrium can even occur between loci on different chromosomes
alleles on different chromosomes can be in LD
Quantifying Linkage Disequilibrium
Linkage Disequilibrium can be thought of as a deviation from a null model of Linkage Equilibrium (|D|)
Linkage Equilibrium assumes: no selection, random mating, free recombination, large populations
Linkage Disequilibrium can be thought of as a measure of the excess of coupling (AB/ab) over repulsion (Ab/aB) gametes
D = 0: two alleles segregate independently -> they are in linkage equilibrium
D > 0: there are more coupling gametes than expected by random assortment
D < 0: there are more repulsion gametes than expected
Linkage equilibrium => strongest possible linkage disequilibrium
LD will break down over time
Factors affecting LD:
bottleneck
assortative mating -> increase LD
Change of LD over time - the effect of recombination
c = recombination fraction between 2 loci / describes degree of recombination in the 2 loci / describes the genetic distance between 2 loci on a map / number of recombinations / fraction of recombinant gametes (Ab|aB) produced in heterozygotes (AB|ab)
ranges from not recombination (c=0) to a maximum (c=0.5, two loci recombine freely)
small c = recombination unlikely -> LD maintained
large c = recombination likely -> LD broken down
Merill - Lecture 2 - Linkage Disequilibrium
Quantitative Genetics
Merill - Lecture 3 - Quantitative Genetics
inheritance of quantitative / continuous traits (not like yes / no, black / white, but like height)
Quantitative traits / characters
usually influenced by both (several) genes and the environment: P = G + E
P = Phenotypic value (can be measured)
G = Genotypic value (sum of the effects of all contributing loci)
E = Environmental deviation (introduces variation, Environment e.g. nutrition, climate, maternal effects, measurement error e.g. for behaviour)
in sexual population we can only measure P; it is normally not possible to estimate G and E directly
Clonal family
identical siblings have same genotype
genetic contribution is the same for siblings from the same (clonal) family
Additive effects
effect of each allele is not affected by what other allele is present at the same locus nor by what alleles are present at other loci
Selection differential (S)
If some members of a population breed and others don’t and you compare the mean phenotypic value for the breeders and the whole population, the difference between them is the selection differential (S).
Quantitative Trait locus mapping (QTL) studies vs. Genome wide Association Study (GWAS)
to map (locate) and to estimate the effects of the underlying genetic variants contributing in a phenotypic trait
both use data on molecular markers (usually SNPs) that are either genotyped within families / pedigrees (QTL mapping) or in a random sample of (unrelated) individuals from a population (GWAS)
QTL:
focus on the co-inheritance of a marker with the phenotypic trait under study
quantitative trait locus = region where a marker co-segregates with a causal allele
a genomic region, not a gene
Abschnitt eines Chromosoms , für den in entsprechenden Studien ein Einfluss auf die Ausprägung eines quantitativen phänotypischen Merkmalsdes betreffenden Organismus nachgewiesen wurde (z.B. Körpergröße)
we only determine effect sizes for significant QTL -> a “winner’s curse”
GWAS:
make use of the historical recombination patterns in a population which lead to linkage disequilibrium between molecular markers and causal alleles
-> QTL mapping studies tend to be more powerful but less precise than GWAS
Beavis effect
the estimates of phenotypic variance associated with one of multiple quantitative trait loci, each of which has a small effect on the trait being studied, are typically significantly inflated if the sample size of organisms in the study is too low (e.g. about 100), but that these estimates are fairly accurate if the number of individuals is much greater (e.g. about 1000)
Speciation
Merill - Lecture 4 - Genetics of Speciation
evolution of new species, the fundamental process that generates biodiversity
Biological Species Concept (Ernst Mayr)
Species are groups of interbreeding populations, which are (normally) reproductively isolated from other such groups
says that gene flow persists within species, but hybridisation and gene flow are absent between species (not always the case tho)
Reproductive barriers: What keeps the species apart?
1) pre-zygotic:
occurs before formation of the zygote and often before mating
stop individuals from divergent populations to reproduce
Geographical / Ecological (don’t meet, can’t mate) or Behavioural, Mechanical (do meet, don’t mate / can’t mate)
2) post-zygotic:
mating occurs but either the hybrids fail to develop or develop with significant genetic problems due to incompatibilities or sterility, or the hybrids develop relatively normally but may suffer a fitness deficit because they are intermediate between two parental phenotypes meaning they are not well suited to either parental environment or are not attractive to other individuals
Hybrid inviability, Gametic incompatibility, Hybrid sterility, Ecological mismatch, Mate choice
How do reproductive barriers evolve?
Allopatric speciation (null model of speciation): situations where prolonged physical barriers impede gene flow between populations (don’t meet)
Peripatric speciation: a small part of a larger population becomes isolated
Ecological speciation: the process by which barriers to gene flow evolve between populations as a result of ecologically based divergent selection
Mutation-order speciation: populations adapting to similar selection pressure by fixing different alleles, and this leads to reproductive isolation
Parapatric speciation: divergence across a continuous population
Sympatric speciation: no extrinsic barrier at all
Reinforcement: increase in pre-zygotic isolation in response to selection against unfit hybrids, a.k.a. the Wallace effect
-> now more common to talk about speciation with and without gene flow
one-allele model vs. two-allele model
one-allele model: reproductive isolation strengthened by substituting same alleles
two-allele model: reproductive isolation strengthened by substituting different alleles
-> speciation with gene flow is greatly facilitated under a one-allele process because recombination cannot break down the association between alleles under direct and indirect selection (meaning speciation easier via one-allele processes)
interbreeding in one-allele model: no dissociation of allels
interbreeding in two-allele model: dissociation of alleles
magic traits
traits that contribute to prezygotic isolation, but which evolve under direct selection, i.e. traits under divergent selection that also influence assortative mating
“classical magic traits”: (normally) ecological traits that also act as mating cues
two criteria for trait to qualify as magic trait:
the magic trait, not a correlated trait (controlled by different genes), must be subject to divergent selection
the magic trait, not a correlated trait, must generate non random mating
problem with magic trait scenario: unless mating preferences are very strong, the LD that emerge may not be especially string and is probably easily broken down
one allele affects two or more alleles
die Ausprägung unterschiedlicher phänotypischer Merkmale, die durch ein einzelnes Gen hervorgerufen wird
one extreme of physical linkage
Dobzhansky-Muller 2-Locus Model
explains how incompatibilities emerge in hybrids without affecting parental species
allopatric vs. sympatric
allopatric: no gene flow
sympatric: potential gene flow
In allopatric speciation, groups from an ancestral population evolve into separate species due to a period of geographical separation.
In sympatric speciation, groups from the same ancestral population evolve into separate species without any geographical separation.
cryptic species
closely related species may appear very similar
convergence between species
meaning they look the same
Protein Evolution
protein evolution typically “simpler” than DNA evolution
proteins generally more conserved throughout evolution and easier to align and compare between distantly related species
DNA more complicated: coding an dnon-coding, within coding synonymous and non-synonymous nucleotide sites
Parsch - Lecture 1 - Protein Evolution
Molecular clock
a figurative term for a technique that uses the mutation rate of biomolecules to deduce the time in prehistory when two or more life forms diverged.
The biomolecular data used for such calculations are usually nucleotide sequences for DNA, RNA, or amino acid sequences for proteins.
does not always tick at the same rate
the molecular clock is constant with time, not with generations
many proteins appear to evolve in a clock-licke manner, but many exceptions found, too
Relative Rate test
to test if the molecular clock really is constant
you need protein sequences from two relatively closely related species and one more distantly related species to be used as an outgroup
if the molecular clock holds, K_AC should be equal to K_BC and thus K_AC - K_BC = 0
Dispersion test
to test the molecular clock
A model of rare, neutral mutations being fixed by drift predicts that the number of substitutions occuring over time should follow a Poisson distribution (mean and variance are equal)
Purines
Parsch - Lecture 2 - DNA Evolution
A & G nucleotides
double-ring chemical structure
Pyrimidines
C & T nucleotides
single ring
Transitions
changes between two nucleotides of the same structural class
A <-> G
C <-> T
Transversions
changes between two nucleotides of different structural classes
A <-> C
A <-> T
G <-> C
G <-> T
Non-synonymous changes
change the amino acid
also called replacements
Synonymous changes
do not change the amino acid
Types of sites with a protein-coding sequence
protein coding sequences made up of codons
in most cases, 1st and 2nd codon positions are degenerate, while 3rd positions are 2- or 4-fold degenerate
in general, 4-fold degenerate sites evolve the fastest and non-degenerate sites evolve the slowest
appears that 4-fold degenerate sites are under little or no selective constraint
much stronger constraint on non-degenerate sites, suggesting that changes at these sites are much more likely to have a negative effect on an organism’s fitness
UTR’s and flanking regions also evolve more slowly than pseudogenes and 4-fold degenrate sites, suggesting that they are under at least some selective constraint - probably for gene regulatory elements
Pseudogenes
genes that typically arise through duplication and are no longer functional
expected to be under no selective constraint and accumulate changes according solely to the mutations rate of the organism
Codon Bias
the synonymous codons for a particular amino acid are not used with equal frequency as would be expected at random
certain codons are “preferred” and are used more frequently
explanation 1: selection favors the use of codons that can be translated quickly and efficiently
highly expressed genes show greater levels of codon bias than genes expressed at low levels
explanation 2: bias in mutation
bias towards G or C
Molecular Phylogenetics (or systematics)
Parsch - Lecture 3 - Molecular Phylogenetics 1
The study of evolutionary relationships among organisms or genes / gene trees using moleculare data (typically portein or DNA sequences) and statistical techniques (also: “tree building”)
Species Tree
show the evolutionary relationships among species
Gene Tree
Show evolutionary relationships based on single genes, or groups of homologous genes. Not necessarily the same as species trees
Homologous genes (homologs)
similar sequence due to common ancestry
Orthologous genes (orthologs)
homologs due to speciation
Paralogous genes (paralogs)
homologs due to gene duplication
Phenetics
organisms grouped by overall similarity
all characters considered
allows paraphyletic groups
Cladistics
organisms grouped by evolutionary relationships using shared, derived characters (a.k.a. “synapomorphies”)
Accepts only monophyletic groups (clades)
Bootstrapping
statistical model: can be applied to distance, parsimony, ML methods
sequence data are re-sampled (with replacement) and a new tree is built: repeat multiple times
greater confidence a tree is correct if it appears more often
Rare genomic changes (RGC’s)
insertion / deletion
intron gain / loss
TE insertion
gene duplication
…
Domestication of Dog
Dog most closely related to wolves
Domestication began ≈15.000 years ago (up to 40.000 years ago)
American Dogs were derived from previously domesticated Eurasion dogs and not domesticated independently in America
American Dogs were closer to Eurasian wolves than to American wolves
Asian Origin of domesticated dogs
Parsch - Lecture 4 - Molecular Phylogenetics 2
mtDNA
~500 bp
maternal inheritance
evolves relatively slowly
microsatellite DNA
short tandemply-repeated sequences
evolve faster than mtDNA and is much more variable within species
inherited from both parents
Domestication of Cats
domestic cats have a Near Eastern origin
Domestication probably began ≈9.000 years ago
Neutral Theory of Molecular Evolution
Parsch - Lecture 5 - Testing the Neutral Theory
states that the molecular polymorphism observed in natural populations is due to neutral meutations under mutation-drift equilibrium
Molecular divergence between species is an extension of this process, caused by neutral mutations going to fixation in one or the other species
states that positive selection need not be invoked to explain molecular polymorphism and divergence
does not state that all possible mutations are neutral, only those that are observed. There may be negative (purifying) selection against mutations that have a deleterious effect on an organism’s fitness. This can explain why different proteins evolve at different rates and why silent substitutions occur more frequently than amino acid replacements
Genetic Hitchhiking and Selective Sweeps
Genetic Hitchhiking
neutral theory predictions for polymorphism and divergence depend only on the effective population size and the mutation rate, not recombination rate
Deviation from neutrality can be explained by “Genetic Hitchhiking”
under this model a positively selected mutations goes to fixation, bringing all linked neutral mutations to fixation with it
Selective Sweep:
Since linkage is stronger in regions of reduced recombination, the effect of reduced polymorphism is strongest in these regions: “selective sweeps”
the process through which a new beneficial mutation that increases its frequency and becomes fixed (i.e., reaches a frequency of 1) in the population leads to the reduction or elimination of genetic variation among nucleotide sequences that are near the mutation.
In selective sweep, positive selection causes the new mutation to reach fixation so quickly that linked alleles can "hitchhike" and also become fixed.
because selective sweeps remove variation in a region of a chromosome, they lead to a reduction in the number of haplotypes
Background selection
describes the loss of genetic diversity at a non-deleterious locus due to negative selection against linked deleterious alleles.
It is one form of linked selection, where the maintenance or removal of an allele from a population is dependent upon the alleles in its linkage group.
The name emphasizes the fact that the genetic background, or genomic environment, of a neutral mutation has a significant impact on whether it will be preserved (genetic hitchhiking) or purged (background selection) from a population
Technically very difficult to distinguish between selective sweeps and background selection experimentally
Great Apes
Parsch - Lecture 6 - Human Evolution
Orangutans
Gorillas
Chimpanzees
Bonobos
Humans
3 main trends of adaptive evolution in the hominin lineage
Bipedality: walking upright
Brain enlargement
Social behaviour
When did the hominin lineage split from our closest relatives (chimpanzees & bonobos)?
~5-6 mio years ago
3 main hypothesis for modern human origin
Candelabra model:
modern humans evolved from H. erectus, but did so independently in Europe, Asia and Africa without gene flow
Multiregional model:
modern human evolved from H. erectur, but there was sufficient gene flow (migration)
Out-of-Africa / replacement model:
modern humans evolved in Africa and spread from there, replacing H. erectus or H. neanderthalensis without interbreeding
-> suggests combination of multiregional and out-of-Africa model
mitochondrial DNA (mtDNA)
single, non-recombining, maternally inherited locus
evolves rapidly
small mtDNA genome is easy to work with, amplify,…
mitochondrial Eve
existed ~200.000 years ago
was African
only woman to have a continuous lineage of daughters going down over the generations
was not
the only woman alive
the only woman in her time to have children
special in terms of fitness
common ancestor of the rest of our genes
Picture of migration
Africa (100.000 years ago) -> SE Asia / Australia (40.000-60.000) -> Europe (40.000) -> North America (20.000) -> South America (13.000 years ago)
Y-Adam
common ancestor of the non-recombining part of human Y-chromosome
lived about 50.000-100.000 years ago in Africa
effective population size of humans
12.500
very low relative to current census population size of > 6 billion
Gene flow
natural populations exist more like a set of sub-populations that are connected by gene flow
gene flow = incorporation of alleles from one population into another
e.g. migration / dispersion of pollen
homogenizes the genetic variability among the sub-populations and maintains the total population as a single species
high gene flow: genetic variation in all sub-populations will be similar
low gene flow: greater variation between the sub-populations than within each sub-population -> in extreme this can lead to genetic incompatibility of sub-populations and speciation
Functional Genomics
Parsch - Lecture 7 - Genomics 1
Transcriptomics
Metabolomics
Phenomics
Interactomics
used to describe how 2 different phenotypes arise from the same genotype (e.g. queen vs. worker bees)
C-value
amount of DNA in a single haploid nucleus
How big is 1Gb
1 Gb = 1.000 Mb = 1.000.000 Kb = 1.000.000.000 bp
C-value paradox
The genome size is not strongly correlated to orgnism complexity
Genome sequencing
Standard: Sanger DNA sequencing methods can only read 500-1000 bp per reaction
clone-by-clone: Genome cloned into large-insert vectors (BACs - bacterial artificial chromosome) ≈100kb -> mapped to form a minimal overlapping set -> each clone is broken up and sequenced individually
shotgun: Genome cloned into small-insert vectors (plasmids) ≈2-10kb -> sequenced at random -> raw sequence is then assembled by computer to reconstruct the genome
Gene prediction (?)
de novo / ab initio prediction: use computer programs to identify genes from raw DNA sequence data. Look for long open reading frames (ORFs) that start with ATG and end with stop codon. Can also incorporate splice signals, or codon bias information, etc.
Comparative prediction: Look for sequences sharing significant homology with other, known genes. Can compare different species. If ORFs are conserved between species, they are likely functional
experimental identification: mRNA is isolated from the organism and converted to cDNAs, then sequenced on a large scale
Protein coding sequence
represents only ~2% of the human genome
repetitive DNA
long stretches of the same DNA sequence repeated many times in tandem
enriched at centromers and telomers and referred to as “heterochromatin”
doesn’t clone easily in bacterial vectors and is mostly excluded from genome projects
transposable elements (TEs)
interspersed repetitive DNA
pieces of DNA that can replicate and move within the genome
sometimes called “jumping genes” or “selfish DNA”
make up about 1/2 of the human genome
pseudogenes
genes that are no longer functional
these are often duplicated genes that are not expressed and / or have a disruptive ORF (internal stop codon or frameshift)
Functional Genomics - Trancriptomics
microarrays
attaching many DNA sequences to a small surface
each unique DNA sequence is placed in a “spot” of known location and there may be thousands (or even millions) of spots on a single array
DNA placed on the array may come from cDNA clones, synthesized oligonucleotides or PCR-amplified genomic DNA
cDNA from two different samples labeles with different fluorescent dye, then mixed in equal amounts and hybridized to the microarray
cDNA will anneal to the DNA spot complementary to their sequence
using laser scanner to quantify the fluorescence of the two dyes and thus measure the relative amount of expression of each gene
e.g. genes with higher expression in sample A have stronger red signal
RNA-seq
millions of short cDNA fragments are sequenced from each sample
mRNA is purified from a sample, reverse transcribed into cDNA, then millions of cDNA are sequenced using next-generation sequencing methods
the number of times a cDNA matching a particular gene is sequenced gives an estimate of that gene’s expression level
Parsch - Lecture 8 - Genomics 2
Functional Genomics - Reverse Genetics (Gene knockout)
start with particular target gene sequence and look for the resulting phenotype when this gene is mutated or its expression is knocked-out
opposite to forward genetics: one knows the mutant phenotype and tries to find the responsible gene
a) homologous recombination:
works well in bacteria, yeast, mouse (& other mammals)
A “knockout” DNA sequence (usually plasmid) that shares homologous end sequences with the target gene is constructed in vitro, then introduced into the cell. In some cases, recombination will occur between the plasmid and the chromosomal DNA. This will result in the corresponding segment of chromosomal DNA being replaces by the knockout sequence
b) CRISPR-Cas
uses bacterial endonuclease (Cas9) and a custom guide RNA (gRNA) to delete or replace a specific target in the genome
works well in almost all types of organisms
c) RNA interference (RNAi)
works well in worm, fly, other insects / plants / mammals
dsRNA complementaey to the target gene is introduced into the cell. This dsRNA activates an innate defense pathway that leads to the degradation of the corresponding mRNA -> PTGS (post translational gene silencing)
the gene is still intact in the nucleus, but its expression is prevented because the mRNA is degraded before it can be translated into protein
Conserved Genes
Conservation across diverse species suggests a shared, important function
not conserved genes may be responsible for phenotypic differences between species
Possibilities following Gene duplication
pseudogenization: one copy loses function through mutation and becomes a pseudogene
Maintenance of two redundant copies: selection favors keeping multiple, redundant copies of the same gene. This could happen if having more of the gene’s RNA or portein is beneficial
neofunctionalization: one copy gains new function that is favoured by selection. This would promote diversification of gene functions and increase gene number over time
subfunctionalization: the original gene had two functions, one of which is lost in each of the two copies. Then both copies are retained, but no new function has been gained
Evolutionary bioinformatics
use bioinformatic methods to extract genome sequence data / transcriptomic data… and use them to test evolutionary hypotheses
Effect of recombination rate on dN/dS
if there is frequent positive selection, we expect a positive correlation between a gene’s dN/dS and the recombination rate of the genomic region where it is located
negative (purifying) selection: expect negative correlation -> because there will be more interference between loci when there is low recombination
if most amino acid replacements are neutral: dN/dS should be not correlated with recombination rate
genes with high expression (e.g. house-keeping genes) have a very low rate of protein evolution (dN/dS)
provides an explanation as to why there may be an evolutionary advantage to genetic recombination.
n a population of finite but effective size which is subject to natural selection, varying extents of linkage disequilibria (LD) will occur. These can be caused by genetic drift or by mutation, and they will tend to slow down the process of evolution by natural selection
This is most easily seen by considering the case of disequilibria caused by mutation: Consider a population of individuals whose genome has only two genes, a and b. If an advantageous mutant (A) of gene a arises in a given individual, that individual's genes will through natural selection become more frequent in the population over time. However, if a separate advantageous mutant (B) of gene b arises before A has gone to fixation, and happens to arise in an individual who does not carry A, then individuals carrying B and individuals carrying A will be in competition. If recombination is present, then individuals carrying both A and B (of genotype AB) will eventually arise. Provided there are no negative epistatic effects of carrying both, individuals of genotype AB will have a greater selective advantage than aB or Ab individuals, and AB will hence go to fixation. However, if there is no recombination, AB individuals can only occur if the latter mutation (B) happens to occur in an Ab individual. The chance of this happening depends on the frequency of new mutations, and on the size of the population, but is in general unlikely unless A is already fixed, or nearly fixed. Hence one should expect the time between the A mutation arising and the population becoming fixed for AB to be much longer in the absence of recombination. Hence recombination allows evolution to progress faster. There tends to be a correlation between the rate of recombination and the likelihood of the preferred haplotype (in the above example labeled as AB) goes into fixation in a population.
Recombination and intron length
intron length is negatively correlated with recombination rate
genes in regions of low recombination have much longer introns than genes in regions of higher recombination -> suggest selection favors shorter introns
Evolutionary Developmental Biology (Evo-Devo)
Parsch - Lecture 9 - Evolutionary Developmental Biology (Evo-Devo)
became possible to identify genes that control developmental processes and to study them comparatively among species
homeotic mutations
mutations that change one body part into another / or duplicate a body part (in the wrong place)
e.g. Ultrabithorax or Antennapedia in fly
Hox genes
Drosophila has 8 homeotic genes, located in 2 complexes in the genome (5 tandem genes from Antennapedia complex and 3 from Bithorax complex)
highly conserved
homeobox (DNA, 180bp): encodes homeodomain, highly conserved region
homeodomain (protein, 60aa): protein domain that binds to DNA, indicating that Hox genes encode transcription factors
physical order of Hox-genes: first gene = head, last gene = tail
2R hypothesis
= two rounds oh whole genome dublication in vertebrate evolution: 1 hox -> 2 hox -> 4 hox
In humans and other vertebrates, many of the Hox genes are present in 4 copies located at different clusters on 4 different chromosomes -> hypothesis that the whole genome underwent 2 rounds of duplication during the evolution of vertebrates (2R hypothesis)
eyeless
vertebrate homolog = Pax6
eyeless = Pax6 mutant (heterozygote)
MADS-box genes
homeotic genes that control floral development
Hox-genes like
MADS-box ≈180bp (60aa)
encodes a DNA-binding domain
MADS-box and homeobox do not share sequence homology
cis- and trans-regulation
Can influence expression of a gene
cis:
physically linked to target gene and close by on the same chromosome
changes in cis-acting sequences only directly affect the expression of one gene
trans:
not linked on target gene
may regulate many different genes on many different chromosomes
changes in trans-acting factors may affect the expression of many genes
morphological evolution occurs primarily through changes in cis-regulatory sequences
because changes in proteins and trans-acting factors are likely to have pleiotropic effects
cis-regulatory changes are more independent and can lead to new expression patterns that don’t interfere with other functions of the target gene
pleiotropic effect
a change that is beneficial to one function / process and may be detrimental to another function / process (places strong constraint on evolution)
Sex determination
a) Environmental sex determination: males and females are genetically identical. Sex is determined by environmental conditions (e.g. temperature at which the eggs are reared. turtles: low temp (<27°C) is male, high (>31°C) is female, intermediate / fluctuating temp produce mix of males and females)
b) Haplodiploidy: females develop from fertilized eggs and are diploid, males develop from unfertilized eggs and are haploid (e.g. honeybees)
c) Male heterogamety: sex is determined by sex chromosomes. Females are XX and Males ar XY (heterogamic)
d) Female heterogamety: sex is determined by sex chromosomes. Females are ZW (heterogamic) and males are ZZ (e.g. birds, butterflies)
Parsch - Lecture 10 - Sex Chromosome Evolution
Sex chromosomes
Y contains < 0.1% of genes in the genome
X contains ~16% of the genes in the genome
Gene density on X is similar to that of autosomes
Sex biased genes
sex biased genes: genes with higher expression in one sex than the other
male-biased genes: tend to be under-represented on the X (“demasculinization”)
female-biased genes: tend to be over-represented on the X (“feminization”)
exception in some tissues, e.g. brain shows excess of male-biased genes on the X
2 evolutionary “effects” that are specific to the X chromosome
Fast-X effect: an expected increase in the rate of adaptive evolution on the X chromosome due to the fixation of recessive, beneficial mutations in hemizygous males (e.g. in Drosophila)
Large-X effect: the X is enriched for loci that cause hybrid incompatibilities, such as hybrid male sterility, suggesting that the X plays a disproportionately large role in speciation - at least in the evolution of postzygotic reproductive isolation (e.g. in hybrids of Drosophila)
2 regulatory mechanisms specific to the X chromosome in male Drosophila
a) x chromosome dosage compensation
in male somatic tissues, expression of the single X chromosome in up-regulated approx. 2-fold
this balances expression with autosomal genes and with the 2 copies of the X in females
up-regulation occurs through the specific binding of an RNA / protein complex (Dosage Compensation Complex, DCC) to many locations across the male X chromosome
Dosage compensation does not appear to occur in the male germline
b) Suppression of X expression in the male germline
in the male germline, the expression of the X chromosome is suppressed
also refereed to as meiotic sex chromosome inactivation (MSCI) (in mammals)
occurs in testes, but not in other tissues
the degree of suppression depends on the expression level of the gene (that is, how strongly its regulatory sequences induce expression in testes)
Comparison with mammalian MSCI
Similarities:
Specific to male germline
may lead to an excess of X-to-autosome functional retrogene copies
Differences:
Inactivation is not complete (expression reduced 3-7-fold)
not clear if it is limited to meiosis (tested genes do not show high expression in pre-meiotic cells)
Sex chromosomes, dosage compensation, and X suppression (MSCI) evolved independently in Drosophila and mammals
CCR5
Parsch - Lecture 11 - Positive Selection in Humans
Resistance to HIV (AIDS) in heterozygotes, resistance to smallpox… (Balancing selection?)
Balancing selection
e.g. Beta-globin
Pos: resistance to malaria in heterozygotes
Neg: sickle-cell anemia in homozygotes
Lactase Persistence (LP)
Pos: ability to digest lactose (milk) as an adult -> positive selection
In europeans: single C -> T nucleotide change ~14kb upstream of the lactate gene (LCT) increases expression in adults
LP has involved independently in the European and African populations
Amylase
copy number variation (CNV): genes present in different numbers of copies in different individuals
higher AMY1 gene copy number -> higher starch diets
Inversion on Chromosome 17
inverted region spans 900kb and contains several genes including MAPT (associated with Parkinson’s disease)
most common form in humans = H1
inverted form = H2 and very rare in most populations except in Europe -> suggests that selection has favoured H2 in European populations
H2 probably ancestral form
women with H2 inversion had more children than women with H1
Prion diseases
caused by misfolded proteins (e.g. Creutzfeld-Jakob Disease in humans)
Prion disease calles Kuru thought to be caused by cannibalism
Polymorphism in the human protein PRNP is associated with CJD and Kuru -> Methionine / valine polymorphism at codon 129. Homozygotes are susceptible to the disease, heterozygotes are resistant
FGFR2 mutations in male germline
mutations in the gene FGFR2 cause Apert Syndrome (AS, malformation disease): dominant, almost always affects children of unaffected parents -> must be caused by new mutations
almost always inherited from the father and frequency increases with father’s age
mutation at same C -> G at position 755 and must have higher mutation rate
mutation may cause sperm stem cells to reproduce at a higher rate
appears to be a case of evolutionary conflict, where a mutation that is positively selected in the male germline has a negative effect on organismal fitness
Epistasis
the fitness effects of one locus are not independent of allelic state of other locus
eine Form der Gen-Interaktion: liegt vor, wenn ein Gen die Unterdrückung der phänotypischen Ausprägung eines anderen Gens bewirken kann
Sexual dimorphism
the condition where the sexes of the same animal and/or plant species exhibit different morphological characteristics, particularly characteristics not directly involved in reproduction.
the systematic difference in form between individuals of different sex in the same species. For example, in some species, including many mammals, the male is larger than the female.
Backcrossing
crossing of a hybrid with one of its parents or an individual genetically similar to its parent, to achieve offspring with a genetic identity closer to that of the parent.
Kreuzung von F1 mit Parental Generation, z.B. Kreuzung weiblich mit Vater oder männlich mit Mutter um Reinerbigkeit zu prüfen
Olfactory receptor
chemoreceptors expressed in the cell membranes of olfactory receptor neurons
responsible for the detection of odorants (for example, compounds that have an odor) which give rise to the sense of smell
Activated olfactory receptors trigger nerve impulses which transmit information about odor to the brain
members of the class A rhodopsin-like family of G protein-coupled receptors (GPCRs)
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