Genetics Notes Part 2

Why do the positions and distances of genes in a genetic map sometimes differ from the positions and distances of the same genes on a physical map?

Rates of crossing over vary somewhat from one part of the chromosome to another

Non-random mating

Remember, we assumed: - A large population of diploid, sexually-reproducing individuals - Non-overlapping generations, Mendelian formation of gametes, and random mating - No mutations, no migration and no natural selection Different types of non-random mating ...

Migration

Remember, we assumed: - A large population of diploid, sexually-reproducing individuals - Non-overlapping generations, Mendelian formation of gametes, and random mating - No mutations, no migration and no natural selection Migration occurs when individuals leave one population and either get absorbed in another population or establish a new population - Migration leads to flow of alleles between populations - Migration (or gene flow) has two consequences: Prevents populations from becoming genetically dissimilar and Increases genetic variation within populations - There may be a strong founder effect when new populations are established - Both the proportion of migrants and the difference in allele frequencies determine how quick allele frequency changes in the receiving population

Mutations

Remember, we assumed: - A large population of diploid, sexually-reproducing individuals - Non-overlapping generations, Mendelian formation of gametes, and random mating - No mutations, no migration and no natural selection Mutations may change the existing alleles to other ones Mutations between existing alleles Forward mutations — 𝑅 → 𝑅′ Reverse mutations — 𝑅′ → 𝑅 Mutations generating novel alleles

Assortative mating

mating choice is based on a particular set of traits Positive assortative mating — similar traits favoured Negative assortative mating — similar traits disfavoured

Non-assortative mating

mating choice is based on relatedness of individuals Inbreeding — mating of related individuals Outcrossing — mating of non-related individuals

Substitutions of single nucleotides

may lead to (a) missense, (b) nonsense, and (c) silent mutations, as well as different phenotypic effects

To study the genome sequence of an extinct species of cave bear, scientists extracted DNA from 40,000-year-old bones of a cave bear to isolate, identify, and sequence the cave-bear DNA. Which approach should be used when their objective was to sequence the genome of the species?

metagenomics This technique allows the identification and genetic analysis of species that cannot be grown in the laboratory and have never been studied by traditional microbiological methods

Convergent Evolution

occurs when similar environmental pressures and natural selection produce similar (analogous) adaptations in organisms from different evolutionary lineages

If two species are similar in terms of morphology, but the molecular data (DNA sequences) show that they are not closely related, then probably their morphological similarity arises from

possession of analogous structures.

What two methods are combined when performing a mutagenesis screen?

random inducement of mutations and mapping with molecular markers

Map-based approaches to whole-genome sequencing

rely on detailed genetic and physical maps to align sequenced fragments

Which is NOT a component used in a sequencing reaction? DNA polymerase ddNTPs dNTPs restriction enzymes

restriction enzymes

Bat 1K

sequence 1000 bat genomes

Shotgun sequencing

sequences a whole genome by breaking the genome into short sequences, sequencing them, and assembling the sequenced contigs on the basis of overlap

Which of these is considered the fourth step in RNA sequencing?

sequencing the cDNA

All of these are methods to study patterns of gene expression EXCEPT microarrays. shotgun sequencing. RNA sequencing. reporter sequence.

shotgun sequencing

Modulators of Ageing

telomeres, mitochondria, blood transcriptome, microbiome, autophagy, inmate immunity

All of these are considered functional genomics projects EXCEPT

the Human Genome Project. This goal of this project was to sequence the entire human genome, and did not focus of the function of any genes.

Genome

the complete instructions for making an organism, consisting of all the genetic material in that organism's chromosomes

taxonomy

the ordered division and naming of organisms

Haplotype

the specific set of SNPs and other genetic variants observed on a chromosome

tautomers

Purines and pyrimidines occur in different forms: i.e., tautomers

shared derived character

is an evolutionary novelty unique to a particular clade - A character can be both ancestral and derived, depending on the context - synapomorph

Ace2

Type of receptor used by SARS CoV 2 to get into cells

genotypic fréquence A guinea pig exhibits three alleles for fur color, A1, A2, and A3, with an allelic frequency of 0.45, 0.37, and 0.18, respectively. What would be the genotypic frequency for A2A3? Round to the nearest hundredth

2pr???? .13

triploid

3 sets of chromosomes - Examples: Parthenogenetic plants, weevils, etc - haploid = one, Examples: Gametophytic stage of mosses, bacteria, etc

Inbreeding

***second important factor for population genetics of small and isolated populations - occurs when individuals mate with their relatives - more likely to occur in small populations - inbreeding increases the degree of homozygosity within the population - inbreeding coefficient measured as F = 1-(Hobs/Hexp) - inbreeding and heterozygosity are thus negatively correlated - as the inbreeding coefficient goes up, heterozygosity goes down - sib-mating for instance F = 0.25 - in a diploid species inbreeding increases the likelihood that an individual will have two alleles that are identical by decent at any given locus - therefore has the effect of increasing homozygosity at all loci - deleterious recessive alleles may then lead to population decline and can culminate in extinction

Australian Lungfish

- 1/5 extant representations of the ancient and once speciose air-breathing Dipnoan lineage - the only remaining austrailian representative of this group and is the most morphologically primative of the extant Dipnoans - now restricted to the SE corner of QLD, naturally occurs in Burnett and Mary Rivers - legally protected, but potentially threatened as its range coincides with some areas that are extensively utilized for agriculture - eg. If irrigation purposes alter the water flow there is the potential for loss of genetic variation by habitat fragmentation. - Spatial isolation of these saltwater intolerant fish in separate catchments might suggest the presence of at least 2 evolutionary significant units. - Minimal genetic differentiation at allozymes and mtDNA loci among populations but deviations from HWE - Surprising given the geographical separation of river catchments - Low genetic variation and lack of sub-division suggests severe population reductions in the recent past, probably through Pleistocene aridity

Signatures of selection in telomere maintenance genes?

- 225 Telomere Maintenance Genes - Mined 52 mammalian genomes and 12 bat genomes - Mechanism of telomere maintenance not yet clear - DNA repair or ALT?

How to read a phylogenetic tree?

- A phylogenetic tree represents a hypothesis about evolutionary relationships • Each branch point represents the divergence of two species • Sister taxa are groups that share an immediate common ancestor - A rooted tree includes a branch to represent the last common ancestor of all taxa in the tree - A basal taxon diverges early in the history of a group and originates near the common ancestor of the group - A polytomy is a branch from which more than two groups emerge

Backbone

- A shared derived character - at branch point which distinguishes vertebrates from invertebrates - A shared ancestral character- -all mammals have backbones, but the presence of a backbone does not distinguish mammals from other vertebrates.

homozygosity

- Alleles may be identical in state or identical by descent

The Molecular Clock Hypothesis

- Amount of genetic difference between sequences is a function of time since separation - Rate of molecular change is constant (enough) to predict times of divergence (within the bounds of particular genes and taxa - The molecular clock does not run as smoothly as neutral theory predicts - Irregularities result from natural selection in which some DNA changes are favored over others - Estimates of evolutionary divergences much older than the fossil record have a high degree of uncertainty - The use of multiple genes may improve estimates

outgroup

- An outgroup is a species or group of species that is closely related to the ingroup, the various species being studied - The outgroup is a group that has diverged before the ingroup - Systematists compare each ingroup species with the outgroup to differentiate between shared derived and shared ancestral characteristics - Characters shared by the outgroup and ingroup are ancestral characters that predate the divergence of both groups from a common ancestor

Do social insects exposed to different environments, and performing different tasks, harbour different gut communities?

- Approached this by: - exposing honey bee colonies to different landscape types - setting up age matched and marked colonies of honey bees - characterising gut microbial communities using amplicon sequencing - significant differences in gut microbial in global comparisons - Core taxa differ in relative abundance between landscape types - Bartonella apis higher in regions distant to OSR - Taxa assigned to the same class (Alphaproteobacetria), higher in OSR - Acetobacteraeae higher in OSR - core honey bee gut bacteria found to be different in bees exposed to different landscapes - What does this mean? - gene functional category found to be enriched in honey bee gut bacteria is carbohydrate metabolism and transport - carbohydrate related function enriched across all bacterial taxa- proteins that show homology to drug resistant efflux pumps - potentially selected upon when bees are exposed to pesticides - B. apis possess gene pathways for the degradation of aromatic compounds, these pathways may facilitate the breakdown of specific pollen components - honey bee workers exposed to different landscape types have different bacterial communities - honey bees performing different behaviours have different bacterial communities

Dom-Recess or Co-Dom Relative allele frequencies

- Assume a population of 𝑵 diploid individuals - For a locus with 3 genotypes, the relative allele frequencies can be computed from the genotype frequencies or the relative genotype frequencies (in part 2): - same basic formula for 6 genotypes, add extra n on top of equation and compute an r as well - could be AA and BB instead of AA and aa Note: 𝑁 = 𝑛RR + 𝑛RS + 𝑛SS and 𝑝 + 𝑞 = 1 - understand equation! diploid = 2 sets of alleles, multiply n by two is two of the same alleles present

X-linked locus Relative allele frequencies

- Assume an population of 𝑵 diploid individuals - For an X-linked locus with 3 genotypes, the relative allele frequencies can be obtained from the genotype frequencies or the relative genotype frequencies: - very similar to above, but 2n on bottom only for female (xx), then add males (xy)

Myotis lucifugus - little brown bat

- Bats represents 25% of all mammalian diversity -Has one of the smallest (mammalian) genome size, therefore represents the lowest amount of DNA required for a functional mammalian genome - This bat's chromosomal structure is very similar to the putative ancestral mammalian chromosomal state - Has the highest metabolic rate of all mammals yet can live for an extremely long time (over 34 years). Perhaps this bat has an unusual way of dealing with cancer-causing free radicals? -Bats may have immunity to certain diseases, therefore if we can understand their genome we can perhaps identify immune system genes that can infer natural immunity?

Cladistics

- Cladistics groups organisms by common descent - A clade is a group of species that includes an ancestral species and all its descendants - Clades can be nested in larger clades, but not all groupings of organisms qualify as clades

Local Clocks?

- Closely related species often share similar properties, likely to have similar rates - For example- murid rodents on average 2-6 times faster than apes and humans - mouse and rat rates are nearly equal

How is conservation genetics done?

- Define populations that are threatened or in danger - form hypotheses about relationships between population and or species and test these hypothesis by examining genetic characteristics of the organisms - Determine the rate at which the exchange of genetic information (gene flow) is occurring - Scientists and managers work together and develop a management strategy

Neutral Variation as an indicator

- Different evolutionary scenarios might be responsible for different amounts of neutral variation in relation to detrimental and adaptive variation - Some positive associations, for example high correlation of microsatellite and MHC loci variation in the desert bighorn sheep - however there are situations where there might be a negative association between neutral and detrimental variation (ie bottlenecks)

Directional mutation pressure

- Directional mutation pressure (DMP) occurs when the rate of mutation from A or T to C or G (𝑢) differs from that in the opposite direction (𝑣), i.e., 𝜇! = 𝑣⁄ 𝑢 + 𝑣 (Sueoka 1988) • 𝜇! is measured by analysing the GC content (Pobs) of protein-coding DNA - DMP varied greatly among mitochondrial cytochrome b genes in animals and plants, ranging from 0.052 ± 0.011 in Apis mellifera (Honey bee) to 0.595 ± 0.025 in Cairina moschata (Muscovy duck). - DMP has had a huge impact on the amino acid composition of the proteins.

Evolutionarily significant units definitions

- ESU = groups of populations with substantial reproductive isolation, which has lead to adaptive differences -ESUs typically characterised by reciprocal monophyly in mtDNA (i.e. If we consider two species, A, and C, to say that they are reciprocally monophyletic means that all of the halplotypes or lineages sampled from species A are more closely related to each other than any haplotype from species C) - MU = managent unit district populations with low levels of gene flow

Honey bees

- Ecologically and economically important pollinator - Experiencing declines in some areas e.g. In Britain numbers have declined by approximately 75% in the past 100 years (Carreck 2008) - Interest in the role of microbes in the health of honey bees and other pollinators is increasing, recent studies have highlighted the possible roles of pathogens for pollinator declines - Microbiota / bacteria can be vertically transmitted from mother to offspring, and can also be acquired environmentally

Effective Population Size

- Effective population size is extremely influential in population genetics in general - Effective population size is often much smaller than the basic number of individuals in a population - three common reasons for this - Uneven sex ratios - Variation in reproductive success - Fluctuating population size

Effects of Gene Flow

- Either dispersal or migration must precede gene flow - Neither mechanism results in gene flow unless individuals reproduce successfully once they have arrived at their new location understanding how individuals, gametes (eg pollen) and genes move between populations is important in conservation biology as it can affect population size, genetic diversity, local adaptation and ultimately speciation

Bee research

- Focus on understanding the evolution and diversification of species - behaviour, sociality, morphology and genetic

Types of mutations — by their phenotype

- Forward mutation — wild type —> mutant type - Reverse mutation — mutant type —> wild type - Synonymous mutation (silent) — codon —> synonymous codon - Nonsynonymous mutation (missense) — amino acid —> another amino acid - Nonsense mutation — sense codon —> nonsense codon (stop codon) - Frameshift mutation — deletion or insertion —> may create a frameshift in mRNA - Neutral mutation — no change in function - Lethal mutation — lethal to the carrier of the mutation - Loss-of-function mutation — effect not lethal but could alter fitness - Gain-of-function mutation — effect not lethal but could alter fitness - Suppressor mutation — hides or suppresses the effect of another mutation

Impact of Migration

- Frequency of bloodgroup B allele as signatures of historic invasions - clinal gradient - The genetic impact of migration depends on the proportion of alleles contributed by migrants and on the difference in frequency between the native population and the immigrants ∆q = m (qm - qo) - qm= migrants, qo = old population (didnt even go over in class)

Gene duplication

- Gene duplication increases the number of genes in the genome, providing more opportunities for evolutionary changes - Repeated gene duplications result in gene families - Like homologous genes, duplicated genes can be traced to a common ancestor

Other types of mutations

- Gene mutations — Duplication, translocation, inversion, deletion, and fusion of genes within chromosomes - Chromosome mutations — Deletion, division, duplication, and fusion of whole chromosomes

genotype frequencies

- Genotype frequencies are computed using the same elementary method irrespective of whether the alleles are codominant, dominant-recessive or silent - Assume a population of 𝑵 diploid individuals. For a single locus with three genotypes, the genotype frequencies are defined as: the number of indicudals of a specific genotype over the N/ number of organisms, both for codominante and recessive

Bats balanced immunity

- Highest diversity of coronaviruses are found in bats - SARS-CoV-2 ancestors found across Asia in Rhinolopus sp - Unconventional Mammalian System for Disease Tolerance - Signature of unique immunity or viral diversity? - BAT1K sequence genomes of potential reservoirsto study how bats can live with coronaviruses

What is the Biomedical Importance of Comparative Genomics?

- Identification of the functional elements in the human genome - including both coding and non- coding - is a key foundation for biomedical research. - One of the most powerful ways to discover these elements is through cross-species comparisons with other mammalian genomes - in effect, deciphering evolution's laboratory notebook containing the results of 100 million years of evolution - Scientists are working to construct a universal tree of all life, which will be refined as new data are collected - "tree of life project"

Division of labour in bees

- Important in the ecological success of social insects - What are the mechanisms underlying division of labour? - Approached this by investigating the task of thermoregulation: - exposed colonies to different temperatures - exposed genetically diverse and non-diverse colonies to different ambient and extreme temperatures - measured effects of temperature during development - conducted comparative study on Asian honey bees in Thailand - Genetic diversity among workers is important for effective division of labour: - genetically different workers (patrilines) have different thresholds for performing the task of fanning - genetically diverse colonies (open mated) are better able to maintain a stable brood nest temperature - Simulations suggested that a large number of patrilines with diverse thresholds results in a more modulated response to changes in the environment

molecular homoplasies

- In distantly related organisms, identical bases in otherwise different sequences may simply be coincidental matches or molecular homoplasies

Binomial Nomenclature

- In the 18th century, Carolus Linnaeus published a system of taxonomy based on resemblances - Two key features of his system remain useful today: two-part names for species and hierarchical classification - The two-part scientific name of a species is called a binomial - The first part of the name is the genus - The second part, called the specific epithet, is unique for each species within the genus - The first letter of the genus is capitalized, and the entire species name is italicized - Both parts together name the species (not the specific epithet alone) - e.g. Homo sapiens

What are mutations?

- Inherited alterations of naturally occurring DNA (not synthetic DNA), which may alter how cells and tissues function, and how each affected individual may behave, survive, and reproduce • Mutations may be spontaneous (tandem repeat expansion) • Mutations may be induced (5-Bromouracil induced)

Insertions and deletions (indels)

- Insertions — introduction of one or several nucleotides at a given site - Deletions — removal of one or several nucleotides at a given site

Suppressor Mutations

- Intragenic suppressor mutations occur in genes containing the mutation being suppressed - Intergenic suppressor mutations occur in genes other than those bearing the original mutations that they suppress - Functional relationship between forward mutations, reverse mutations, and suppressor mutations may be complex - Phenotypic consequences of different mutations are wide-ranging and may impart different levels of fitness to the carrier of these mutations — depending, of course, on external variables

Founder Effect

- It is the loss of genetic variation that a new population may experience when it is established by a small set of individuals - It may lead to a disproportionately high abundance of otherwise rare alleles

Tests of molecular clock

- Likelihood ratio test • identifies deviance from clock but not the deviant sequences - Relative rates tests • compares rates of sister nodes using an outgroup - Tajima test • Number of sites in which character shared by outgroup andonly one of two ingroups should be equal for both ingroups - Branch length test • deviation of distance from root to leaf compared to averagedistance

Hierarchical Classification

- Linnaeus introduced a system for grouping species in increasingly broad categories - The taxonomic groups from broad to narrow are domain, kingdom, phylum, class, order, family, genus, and species - A taxonomic unit at any level of hierarchy is called a taxon - The broader taxa are not comparable between lineages - For example, an order of snails has less genetic diversity than an order of mammals

Yang et al Adaptive Variation

- ML analysis of the lysine gene sequence, that there is significant variation in selective pressure among sites - many aa sites are under strong purifying (negative) selection with the non- synonymous rate close to 0 - while some other sites are under diversifying selection - with the non- synonymous rate elevated to more than three times the synonymous rate - purifying selection operates on conserved sites in all of the Haliotis lineages - variation in selective pressure seem to be due to the presence or absence of diversifying selective pressure - so there is variation, but what caused this variation? - one hypothesis is population size fluctuation - the importance of selection relative to random drift increases with population size. - Favorable alleles that have become fixed, i.e. have undergone a selective sweep, are expected to show low variation at tightly linked markers - e.g. alleles at the G6PDH locus in humans that confer malarial resistance show patterns deviating from the neutral expectation - Significantly reduced variability of microsatellites adjacent to the G6PDH locus

Variations in DHODH associated with Miller Syndrome

- Miller syndrome is a rare genetic disorder (distinctive craniofacial malformations that occur in association with limb abnormalities) - 50% of mutations are found at completely conserved positions in over 46 vertebrates - These sites evolve 40% slower than sites in DHODH associated with non-disease polymorphisms - 10 different mutations in DHODHgene have been shown to beassociated with disease

Molecular clocks

- Molecular clocks help track evolutionary time, Prediction of time from molecular divergence -A molecular clock uses constant rates of evolution in some genes to estimate the absolute time of evolutionary change - To extend molecular phylogenies beyond the fossil record, we must make an assumption about how change occurs over time - ' if DNA accumulates mutations at a constant rate, then you should be able to measure the differences between the DNA from two present-day species and extrapolate back to a time when the DNA was identical - to when one species became two' - Molecular divergence is ROUGHLY correlated with divergence of time -In orthologous genes, nucleotide substitutions are proportional to the time since they last shared a common ancestor - In paralogous genes, nucleotide substitutions are proportional to the time since the genes became duplicated - Molecular clocks are calibrated against branches whose dates are known from the fossil record - Individual genes vary in how clock like they are

Gut microbial community examples

- Nasonia wasps - beneficial gut bacteria instrumental in the speciation process (Brucker et al. 2013) - Bumblebees - specific microbiota protects against the widespread natural parasite Crithidia bombi (Koch and Schmid-Hempel 2011) - Termites - reduced gut microbial diversity in reproductives causes reduced colony growth and colony fitness (Rosengaus et al. 2011)

A Genome Revolution in Biology and Medicine

- New technologies (e.g. next-generation sequencing) can lead to collecting huge storehouses of data, which will be used to change biological research and medicine - 13-year-long Human Genome Project (cost $1 billion), completed in 2003 - January 2014, company Illumina announced the $1,000 human genome - January 2017, company Illumina announced the $100 human genome - Getting data is faster and cheaper than ever!

Bat Telomeres

- No relationship between Telomere length and age in Myotis species - Telomerase is not expressed in Myotis myotis blood or wing transcriptome - Genomic and transcriptomic analyses implicated enhanced DNA repair in the evolution of exceptional longevity in Myotis bats - Implicates ALT as maintenance mechanism

Genetic Drift

- Occurs because reproductive success within a population is variable - therefore not all alleles will be reproduced to the same extent - Each generation a random fraction of the population passes on genes to the next generation - Chance alone can result in changes in allele frequency - effects of drift are most profound in small populations where without selection, drift will drive each allele to either fixation or extinction within a relatively short period. - in larger populations it takes longer for effects to become pronounced - If we draw gametes at random from a population, there will be a lot more variation in the frequency of a particular allele in small populations or samples, than large populations - After a number of generations some alleles go to fixation while others are lost by this random process of sampling - Once the population reaches such a fixation state, it is stuck. Only new mutations or migrants can reintroduce variation

Tandem repeats

- Occurs when when small motifs are repeated, again and again - Tend to grow in length until something happens to the individual - Mutations may involve substitutions, deletions, and insertions of single nucleotides, as well as tandem duplications of small motifs, but may also involve larger blocks of DNA, ranging in size from exons to whole chromosomes

Is Inbreeding only bad?

- Outcrossing reverses the deleterious effects of inbreeding - One assumes deleterious recessives in habitually inbreeding species have mostly been purged by selection - inbreeding increases the homozygosity of recessive deleterious alleles, therefore the associated deleterious traits are more likely to be expressed - these traits will then be selected against, which can lead to the elimination or purging of the deleterious alleles from the population - this process is particularly effective against alleles that are lethal in the homozygous state - purging is unlikely to have much effect on alleles that are mildly deleterious - these alleles may become fixed in a small population following drift - purging cannot get rid of the effects of inbreeding that are associated with heterozygote advantage - thus effectiveness of purging remains debatable!

minION

- Oxford nanopore gene reader that can sequence DNA, very tiny - can easily do in the field, don't need a lab

Sorting Homology from Analogy

- Phenotypic and genetic similarities due to shared ancestry are called homologies - Organisms with similar morphologies or DNA sequences are likely to be more closely related than organisms with different structures or sequences BUT: - When constructing a phylogeny, systematists need to distinguish whether a similarity is the result of homology/analogy - Homology is similarity due to shared ancestry - Analogy is similarity due to convergent evolution - COMBINED FORCES = MOST ACCURATE IMAGE

Applying a Molecular Clock: The Originof HIV

- Phylogenetic analysis shows that HIV is descended from viruses that infect chimpanzees and other primates - When? HIV spread to humans more than once - Comparison of HIV samples shows that the virus evolved in a very clocklike way - strain spread to humans during 1930s discovered by the application of molecular clocks - due to samples of virus in different years

Applying Phylogenies

- Phylogeny provides important information about similar characteristics in closely related species • A phylogeny was used to identify the species of whale from which 'whale meat' originated (PCR in hotel room)

How does genetic diversity become reduced?

- Populations can undergo loss of genetic diversity through changes in migration, selective pressures, geographical isolation and founder effects - All these factors increase the effects of random genetic drift - Gene flow and genetic drift are opposing forces, so that an equilibrium can be established if populations are interconnected - Habitat fragmentation makes populations more susceptible to genetic drift

Why is genetic diversity important?

- Populations with high genetic diversity have a greater chance of adapting to new environmental conditions - If genetic diversity is very low, none of the individuals may have the characteristics needed to cope with new conditions, so they could be suddenly wiped out - Once gene variants are lost, they cannot be recovered

How do random mating and Mendelian principles influence the frequencies of alleles and genotypes? How do segregation of alleles during gamete formation and combination of gametes from males and females shape the gene pool?

- Random mating refers to matings in a population that occur in proportion to their genotypic frequencies. For example, if the genotypic frequencies in a population are MM=0.83, MN=0.16 and NN=0.01 then we would expect that 68.9% (0.83 x 0.83 X 100) of the matings would occur between MM individuals - The law of segregation states that each individual that is a diploid has a pair of alleles (copy) for a particular trait. In essence, the law states that copies of genes separate or segregate so that each gamete receives only one allele (one from mom, one from dad) - unique from both mother and father fosters diversity - Mendel's law of independent assortment states that the alleles of two (or more) different genes get sorted into gametes independently of one another. In other words, the allele a gamete receives for one gene does not influence the allele received for another gene (50/50 one allele over the other)

Protein Variability

- Rate constancy does not hold across different protein types - However.- Each protein does appear to have a characteristic rate of evolution - immune system genes change constantly

Rate Heterogeneity

- Rate of molecular evolution can differ between- nucleotide positions- genes- genomic regions- genomes within species (nuclear vs organelle)- species- over time• - If not considered, introduces bias into time estimates

Red Wolf

- Red wolf was placed into a captive breeding program in 1974, by 1975 it was extinct in the wild - early data suggested that red wolves hybridized with coyotes - Wayne and Jenks found that red wolves have either a gray wolf or a coyote mtDNA, indicating that the red wolf "species" is entirely a hybrid. What should we protect? If the species isn't really a clear entity phylogenetically, does it deserve a conservation/captive breeding effort?

Recombination and sociality

- Social insects have exceptionally high rates of crossing over - Honey bee known to have one of the highest recombination rates in any plant or animal (19-37cM/Mb) - Recombination rate associated with level of sociality in hymenoptera - But evolutionary causes of these extreme recombination rates are unknown - use whole genome resequencing of a social and solitary bee - estimate population-scale recombination rate across regions - analyse factors that control recombination rate in the two bees - Average cross over rate is 24 x higher in the honey bee - Confirms that recombination is extremely elevated in the honey bee - Recombination rate in the leaf-cutter bee is in the range of the majority of plants and animals - But higher selection pressures in honey bees and social insects may be driving the tremendous differences in genome wide recombination rate

Causes of mutations

- Spontaneous replication errors — typically due to Tautomeric shifts, Mispairing due to other structures, Incorporation errors and replication errors, Causes of deletions and insertions (Strand slippage/Unequal crossing over) - Spontaneous chemical changes - Chemically induced mutations - Radiation - Spontaneous replication errors is a variety of occasional errors that arise during replication. The errors cannot be avoided due to the fact that the nucleotides are flexible building block

phenotypes

- Strictly speaking, a phenotype is the outward manifestation of a genotype - Simple, single-gene traits — e.g., ABO, Rh+/Rh-, MN blood groups in humans - Complex, multigene traits — e.g., fur colour, quantitative genetic traits (cattle) BUT epigenetic effects may mask the manifestation of a genotype

Grizzly bears

- Study in 1995 used micosats to look at paternity and reproduction in Arctic Grizzly bears - 12 fathers for 36 of 57 known offspring - unsampled breeding males probably utilised the area as a small part of their home range - females tend to remain within relatively small home ranges and their female offspring establish adjacent or overlapping home ranges - male offspring leave the natal area after weaning and establish much larger home ranges as adults - males may travel hundreds of kilometres. - Evidence that males from a large surrounding area are breeding successfully with females in the study area - Since females tend to be strongly philopatric, male behaviour is the primary mechanism for maintaining genetic diversity - Further studies to measure the relative degree of genetic diversity in more isolated populations

Fine tuned disease prediction

- Subramanian and Kumar (2006): Evolutionary anatomies of positions and types of disease-associated and neutral amino acid mutations in the human genome - 541 genes analyzed in human, mice, chicken, fungus - Disease-Associated Mutations: in conserved regions• non-synonymous SNPs in regions under positive/relaxeds election - Comparative studies can help categorizing SNPs into benign, possibly-damaging, and probably-damaging categories

While constructing a phylogenetic tree

- Systematists can never be sure of finding the best tree in a large data set - for 50 species, there are 3 × 1076 different ways to form a tree. - They narrow possibilities by applying the principles of maximum parsimony and maximum likelihood

Linking Classification and Phylogeny

- Systematists depict evolutionary relationships in branching phylogenetic trees - Linnaean classification and phylogeny can differ from each other - convergent evolution, can look morphologically similar but genetically different

Evaluating Molecular Homologies

- Systematists use computer programs and mathematical tools when analyzing comparable DNA segments from different organisms - To deal with deletions an insertions throughout time, researchers use computer programs to analyze comparable DNA sequences of differing lengths and align them appropriately - It is also important to distinguish homology from analogy in molecular similarities • Mathematical tools help to identify molecular homoplasies, or coincidences • Molecular systematics uses DNA and other molecular data to determine evolutionary relationships

Case study: Olfactory Receptor Genes

- The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes - Largest gene family in the mammalian genome (many duplicated genes) - Approx. 1000 OR genes each 1kb long, intronless - Class I, >51 (currently 51-68), Fish- water borne odours - Class II, 1-50 (currently 1-14) Tetrapods- air borne odours - only one gene expressed in each olfactory nerve, many nerves = can bind all different smells - Study: compared the functional OR gene repertoires from 50 mammalian genomes. - Why?: To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families - Heatmap displaying the relative percentage of functional genes in each OR gene family of different mammalian genomes, mapped onto the consensus phylogenetic tree for mammals - Heatmap of the informative OR gene families partitioned by ecological group - different families have different amounts of functional genes based on ecotype - semi-aquatic = hard to discern cause have both - Loss of past function in evolution of terrestrial-acquatic environment

Phylogenetic bracketing

- The best hypotheses for phylogenetic trees fit the most data: morphological, molecular, and fossil - Phylogenetic bracketing allows us to predict features of an ancestor from features of its descendants - For example, phylogenetic bracketing allows us to infer characteristics of dinosaurs - Birds and crocodiles share several features: four- chambered hearts, nest building, and brooding. These characteristics likely evolved in a common ancestor and were shared by all of its descendants, including dinosaurs - The fossil record supports nest building and brooding in dinosaurs

How do Telomeres contribute to Ageing?

- The cell's machinery cannot replicate right to the end of the chromosome. - Everytime a cell divides telomeres get shorter - Stops cells replicating when too short - Drives ageing - Telomeres do not shorten with age in longest lived bat genera

genotypes

- The set of alleles at a locus (or sets of alleles at loci) in a given individual - Genotypes are combinations of alleles from the same locus, usually in the nuclear genome of a diploid or polyploid individual - Haploid organisms — e.g., bacteria (e.g., R, S, r, •) - Diploid organisms — e.g., humans (e.g., RR, RS, Rr, R•, Rr, S•, r•, ••) - Polyploid organisms — e.g., tetraploid and hexaploidy forms of wheat

Types of Variation

- Three types of genetic variation are important for conservation genetic issues I. Neutral Variation II. Detrimental Variation III. Adaptive Variation - Neutral molecular variation used to predict the amount and significance of detrimental and adaptive variation

Out-group comparison

- To study the relationships among an ingroup of five vertebrates on a cladogram, an animal called the lancelet is a good choice (member of Chordata, that lacks a backbone). - Backbone, shared by all members of the ingroup but not the outgroup, is a useful character for the whole ingroup. - The presence of hinged jaws, absent in lampreys and present in the other ingroup taxa, helps to identify the earliest branch in the vertebrate cladogram, etc..

Simple base substitutions

- Transitions — purine-to-purine or pyrimidine-to-pyrimidine (𝐴 ↔ 𝐺 or 𝐶 ↔ 𝑇) - Transversions — purine-to pyrimidine (𝐴 ↔ 𝐶, 𝐴 ↔ 𝑇, 𝐺 ↔ 𝐶 or 𝐺 ↔ 𝑇) -Mutations are inherited changes that occur in natural DNA. They are essential to all forms of life. Mutations may occur in somatic DNA, in which case they may affect the cell, tissue or individual, or in germline DNA, in which case they may be passed on to the next generation (via the gametes)

Shared Ancestral and Shared Derived Characters

- When inferring evolutionary relationships, it is useful to know in which clade a shared derived character first appeared - The status of a shared derived character versus a shared ancestral character is relative, depending on the level at which the analysis is being performed. - The presence of hair is a good character to use to distinguish the clade of mammals from other vertebrates. Hair is a shared derived character that uniquely identifies mammals.

Cooperation and sociality - honey bees

- Why do honey bee queens mate multiply? - Is there a benefit to genetic diversity within colonies? - Do patrilines vary in their task threshold? - If so does it have a colony level benefit? Hamilton's seminal papers revolutionised our understanding of evolution by explaining this paradox of unsterile bees via kin selection - i.e. where individuals gain fitness by helping their relatives - division of labor of forging and tending to the queen divided by age, ebnvironment and genotype

Bacterial associations

- a low oral dose of a bacterium produces anxiety-like behaviour in mice via the gut - brain pathway - probiotic bacteria influence emotional behaviour in mice - changes in the diet of rodents, which considerably alter the composition of the microbiome, have also been shown to improve memory and learning - in wild red squirrels with elevated stress levels, there is a concomitant reduction in the diversity of the oral microbial community - bacteria in the locust gut produce a key component of the pheromone derived from their faecal pellets that promotes aggregation behaviour in locusts - experimental depletion of a key gut symbiont of stinkbug nymphs results in the occurrence of wandering nymphs, whereas nymphs infected with sufficient amounts of the symbiont rest

Variation in reproductive success

- also decreases the effective population size relative to the actual number of individuals in the population - e.g. in steel head trout populations when the trout population is at high density, females have increased competition for males, spawning and other resources - successful competitors will produce large numbers of offspring, whereas the less successful may fail to reproduce - However in other species variation in reproductive success may have relatively little influence on the effective population size - variation in reproductive success may be highest in clonal species - e.g. in freshwater bryozoans (moss animals) selection during the growing season means that some clones are eliminated whereas others reproduce a lot - therefore the basic number of individuals in the population may be huge by the end of the growing season - BUT because clonal selection is decreasing the proportion of different genotypes throughout the summer, the variation in reproductive success must be substantial - some clones produce no offspring whereas others produce large numbers therefore in extreme cases some populations of bryozoans and other clonal taxa may become dominated by single clone that experiences all of the reproductive success within that population.

Bat and Bird Wings

- bats related closely to horses - Bat and bird wings are homologous as forelimbs, but analogous as functional wings - Analogous structures or molecular sequences that evolved independently are also called homoplasies - Homology can be distinguished from analogy by comparing fossil evidence and the degree of complexity - The more complex two similar structures are, the more likely it is that they are homologous - have the same forelimbs, but derived wings separately

Rate Heterogeneity among lineages

- cause, reason - Repair mechanismse, e.g. RNA viruses have error-prone polymerases - Metabolic rate, More free radicals - Generation time, Copies DNA more frequently - Population size, Affects mutation fixation rate, Genetic drift more likely to fix neutral alleles in small population - Strength of selection changes over time, 1. new role/environment, 2. gene duplication, 3. change in another gene

Specific deleterious variants

- characterization of genes with detrimental effects segregating in endangered species is possible - can map genes affecting fitness related traits - ex. chondrodystrophy in california condors

Dusky Seaside Sparrow

- declined in 1960s, only 6 left in 1980 (all male) - captive breeding program was initiated and captive Scott's seaside sparrow was chosen as the females. - but Dusky and Scott's seaside sparrows were members of different clades on the phylogeny of these sparrows - more detailed phylogenetic knowledge of endangered species would have lead to different management decisions

Evolutionarily significant units

- determine is populations are fixed for different alleles or mtDNA haplotypes - hybrids are a bit more problematic (narrow hybrid zones that have been stable for many years are often adaptive and may be considered ESU) - but invasive species may threaten the genetic integrity of endemic species through hybridization (NZ mallard ducks have hybridizes with native grey ducks and no pure grey duck population) - In cases like this one option may be to eliminate populations of the invasive species and its hybrids, if this unrealistic, the protection of hybrids may be the only way to preserve any of the threatened species' alleles - when populations 'at risk' are identified (eg. at risk of inbreeding depression) management strategies can be drawn up to increase their chances of long-term survival - when migrants are translocated from one population to another they will often introduce new alleles into the recipient population - if this results in a reduction of inbreeding depression it is known as genetic rescue - hybrid vigour can result from the production of relatively fit heterozygous individuals, or, more likely, the masking of deleterious alleles - but if a species is not going to be able to survive in the wild then the only way it can be saved from extinction is through captive breeding

Importance of Accurate Taxonomy

- distinct groups of sphenodon in NZ - many inapropriatate conservation decisions can be made if the status of the taxa is correct

Arabian Oryx

- endangered in 1960, should have low genetic variation - MHC alleles only had 3 versions left, but all very different from each other in genetic history

Bats as an Unconventional Mammalian System for Healthy Ageing

- extended lifespans, Myotis brandtii Lifespan >41 yrs Weight ~7g - very high longevity ration and very small body mass

Dominance

- favourable alleles at a locus are usually dominant and the deleterious alleles have been maintained within the population because they are recessive - increased homozygosity resulting from inbreeding means that deleterious alleles are more likely to occur as homozygotes - when this happens their effect cannot be masked by the dominant favourable allele, which results in inbreeding depression

Australian Living Fossil Ant (macrops)

- female short-winged with low dispersal power - male have bigger wings, can fly longer distances - more dispersal by males - 3 populations (penning, poacher, Lake gilles) S Australia - sites within populations separated by 2-10 km - sample size 20-35 per site with different colonies - mitochondrial dna inherited maternally - lots of diversity between areas in mitochondrial DNA network (females can't migrate between pop easily) - gene flow not strongly reduced in 2-10 km range due to dispersing males - low dispersal of newly mated queens leads to high mtDNA differenciation - Lack of congruence between nuclear and mitochonterdrial markers suggest male biased gene flow

Fluctuating population size

- fluctuations in the actual number of individuals in a population can have a lasting effect on the effective population size - a survey of multiple taxa suggested that fluctuations in population size is the most important driver of reduced effective population size compared with the actual population size - a population crash in one year may have a lasting effect even if the population subsequently recovers - this kind of population crash is called a bottleneck and can result from a number of different factors eg. environmental disasters, over hunting or disease

Uneven sex ratios

- generally reduce the effective population size - evidence for parental manipulation eg. in birds - may be a response to environmental constraints - even if the overall ratio in a population is equal, the ratio of breeding adults may be unequal - e.g. elephant seals there is fierce fighting between males for access to harems - therefore only a handful of dominant males in each population will contribute their genes to the next generation - by comparison the majority of females reproduce therefore the result is an effectively female biased sex ratio

barcoded samples sequenced with Illumina MiSeq

- generate sequencing library of a specific orthologous region

The most important feature that permits a gene to actas a molecular clock is:

- having a reliable average rate of mutation

Does purging really occur?

- in insects there is some evidence that purging is responsible for the relatively low levels of inbreeding that have been found in haplodiploid compared with diploid species - males are haploid - therefore can purge genetic load easily as in these haploid males deleterious recessive alleles cannot be masked Conclude that - - Purging does occur, however, the effect is highly variable - Proposal: deliberately inbreed captive populations to purge their genetic load! - Effect in captive animals not high enough to recommend as a useful management strategy - Many biologists believe that the risks associated with this outweigh the potential benefits - eg. when inbreeding depression was monitored over 10 generations of inbreeding in 3 subspecies of wild mice 1 - showed a reduction in inbreeding depression 2 - showed an increase in inbreeding depression 3 - showed no change - these differences may depend at least partly on whether populations have experience past cases of inbreeding and purging in the wild - therefore it seems that deliberate attempts at purging are a fairly desperate strategy for reducing inbreeding depression

Gene Flow Patterns

- in terns of genetic diversity and conservation - macrops, like many species in AUS are likely to have severe habitat fragmentation because of use of agriculture - populations often exist on small patches of remnant roadsides mallee - which make up a significant proportion of the species remaining habitat - But the status of macrops as an endangered species has been uncertain because of its extremely cryptic lifestyle - now untrue - Genetic data are therefore very helpful to shed new light on the conservation status of the species - appreciable levels of genetic variation exist in all three main populations - Macrops has higher microsat diversity than was found in small and geographically isolated populations of Formica cinerea (ant) in Europe. - the extent of genetic diversity in natural populations of macrops does not show any signs of reduction of genetic variation - effective population sizes in individual habitat patches is greater than 1000 - which indicates that the species still occurs in reasonable numbers. - the occurrences of macrops in small patches does not appear to be a particular threat to the species survival = not endangered

Gut microbial community Bee

- key components in the ecological and evolutionary success of animals - can benefit host by helping to digest food, detoxify harmful molecules, protect against pathogens and parasites, modulate development and immunity - only beginning to understand many of the causes and consequences of changes in the gut bacterial community

Meiotic recombination

- key process that occurs in sexually producing organisms - important effects on evolution and genome organization - results in the shuffling of allele combinations in offspring - breaking up existing allele combinations and creating novel ones

chondrodystrophy in california condors

- last wild one in captivity in 1987 - captive breeding successful and reintroduction efforts began 1999 - However in 2000 it was reported that 5 out of 169 fertile California Condor eggs laid in captivity have exhibited chondrodystrophy, - a lethal form of dwarfism - pedigree records indicate that this chondrodystrophy, like similar conditions in chickens, turkeys and quails, is probably inherited as an autosomal recessive allele - estimates of the frequency of the putative allele were about 9% - high frequency probably due to a founder effect. - genome projects of major importance to provide info about homologous genes - documented examples of inherited disorders in endangered species important to assess consequences for reintroductions to the wild

Haliotis (or abalone)

- marine mollusks, spawn their gametes into seawater where fertilization and embryogenesis occur - many simpatico abalone species overlap in depth donation and reproductive seasonality and yet they maintain themselves as distinct species - in abalone, the lysin protein on the surface of the sperm help to make a hole in the protective surface of the egg so that there is contact between the sperm and the lipid membrane of the egg directly, and there are differences in this protein from species to species - even in closely related species of abalone there are differences in the sequences of their lysin proteins - so sperm are better at fertilizing eggs of their same species - what has been found in the lysin gene is that at some sites there are higher nonsynonymous than synonymous substitution rates, which as we just heard, provides evidence for adaptive evolution - However the exact selective pressure remains elusive

Neutral Variation

- molecular variation thought to be mostly nuetral - small pops are especially prone to genetic drift while selection on allele frequencies may become negligible - Genetic variants are more likely to be effectively neutral in endangered than in common species

We can fight cancer by targeting tumour specificmutations... but which mutations do we want to target

- need to target close to trunk, not branching mutations that keep on growing

Preble's meadow jumping mouse

- occurs on real estate land - but not on threatened list due to genetic study, not different from other jumping mice

Molecular clocks are based on the idea that _____

- on average neutral mutations arise at a constant rate

Genetic Restoration of the Florida Panther

- pops of some endangered species seems to process a high frequency of deleterious genetic variants (ie Florida Panther) - genetic drift has fixed a suite of potentially deleterious traits, such as cowlick on the back and a kinked tail - microsatellite variation is the lowest among other North American puma populations - by introducing Texas cougars the frequency of detrimental traits could be greatly reduce - restoration of genetic fitness by only 20% of initial outside gene flow and 2.5 % every generation - one concern about this approach is that any locally adapted alleles could be swamped by outside gene flow

SARS-CoV-2

- probable pangolin origin

Adaptive Variation

- produces advantage in fitness - insights can come from observed patters of DNA variation, such a substitution rates (syn vs nonsyn) and the patterns of sequence variation within and between species - for instance: levels of variation within and between species should be correlated under neutrality - positive natural selection will alter the ratio of non-synonymous to synonymous substitutions - significantly higher non-synonymous than synonymous rates are evidence for molecular adaptation - using techniques several genes appear to show adaptive variation

Population Bottlenecks

- reduces effective population size and overall genetic diversity - important determinant of population genetic diversity because rare alleles will be lost - because long term demographic data are often not available - have to infer relationships between bottlenecks and genetic variation when studying a genetically depauperate population that has no record = detecting past reduction in pop size is not usually easy - severity depends on size of reduction and speed of recovery - initial loss of alleles is proportional to the reduction in pop size - genetic drift means that diversity will keep decreasing while population size is low - often associated with a drop in expected heterozygosity because fewer alleles typically lead to reduced expectations of heterozygosity under Hardy-Weinberg Equilibrium - if samples are available from 2 or more generations then it can be possible to infer past bottlenecks from the variation in allele frequency between generations

Phylogenies

- show evolutionary relationships • Phylogeny is the evolutionary history of a species or group of species. • This evolutionary history of a group of organisms can be represented in a diagram called a phylogenetic tree. -Systematics uses fossil, molecular, and genetic data to infer evolutionary relationships

Wright-Fisher model

- the amount of drift is inversely proportional to the population size, small populations are prone to random changes

the $1000 genome controversy

- the bottleneck is bioinformatics - sequencing cost drops massively, but informatics cost only drops a little

Illumina sequencing of community amplicons

- useful to reduce genome complexity - characterise bacteria symbionts present - reliable representation of bacteria present in the entire community

Detrimental Variation

- variation that has a negative effect on fitness - often brought into pop by mutation, sometimes increased by genetic drift - Levels of inbreeding depression and genetic load differ according to population structure

Overdominance or heterozygote advantage

- where individuals that are heterozygous at a particular locus have a higher fitness than individuals that are homozygous for either allele e.g. sickle cell anaemia - heterozygotes are resistant to malaria

Yuen et al. Nature Neuroscience

- whole-genome sequences from 5,193 (!!!) individuals, about half of whom have autism - Largest study of its kind: through analysis of mutations specific to people with autism, 18 new genes identified

Overall equations

- with genotypic frequency/relative genotypic frequency (frequency of Aa), you can find allelle frequency (p/q) (frequency of A or frequency of a) - then use punnet square to multiply frequencies to find next generation genotypic frequencies - all equations above

Blindness and Deafness

-In 2009, the WHO estimated that 314 millionpeople worldwide are visually impaired and 45 million are blind - 1 in 1000 newborns are affected and > 50% of individuals >80 yearsof age have hearing impairment - Only 10% of these people know their underlying genetic disorder - Although 50-90% of the causal genes have been identified, the majority of disease causing single-nucleotide polymorphisms (SNPs) and crucial genomic regions that lead to inherited blindness are still not known

Neutral theory

-Neutral theory states that much evolutionary change in genes and proteins has no effect on fitness and is not influenced by natural selection - It states that the rate of molecular change in these genes and proteins should be regular like a clock

If the population of fruit flies has an initial frequency of AdhA/AdhA equal to 0.35, what will be the frequency of AdhA in the next generation when alcohol is present?

.42, p2, 2pq, and q2, p = .35 is given, AB = 2pq, can calc that =genotype types all divided by the most prolific to get frequency, fitness times frequency, then divide by mean fitness?

premises for population genetics

1) Many species display phenotypic differences within and among their populations 2) Many phenotypic differences are inherited, implying genotypic differences within and among in these populations 3) Genotypic differences arise from allelic variation in the gene pools of populations 4) Mutations create new alleles and may increase allelic diversity in these gene pools 5) Natural selection acts at the phenotypic level and may alter the gene pool 6) Other factors may alter the gene pool (e.g., inbreeding, migration, genetic drift) —ergo— We may acquire detailed information about the structures, dynamics, and evolution of populations by studying the gene pools of populations

Which of the following is NOT a shared ancestral character? 1. the ability to swim in dolphins and sharks 2. The production of milk in humans and cats 3.the ability to fly in eagles and pigeons 4.the laying of eggs with shells in snakes and lizards 5. all of the above are synapomorphies

1. ability to swim in dolphins and sharks was not a trait derived from an immediate common ancestor swimming developed independently numerous times probably as a result of convergent evolution or reversal evolution

Bats

1462 species - Only true flying mammal - Unique Immunity to Ebola SARS MERS Marburg Covid- 19? - Use bats as an alternative model system to uncover the molecular pathways that underlie extraordinary ageing and disease tolerance in mammals. = Need Exquisite Genomes (Bat 1K)

Bat 1 K finished phase 1

21 families have been collected and sequenced - Need longitudinal mark recapture field studies + New molecular methods

Scientists believe they have found the Loch Ness monster by analyzing samples of eDNA from the River Ness in Scotland. Among the 15 species of fish and the 3000 types of bacteria identified in the water, an unidentified sequence was also obtained. Unidentified sequence3' TGC CAC CCC GGC ACC GCC CTG TGA TCA CAC CTT ATG GAG AGA CAA 5' Using the same forward and reverse primers to isolate a conserved region of DNA from each species, the scientists compared the unidentified sequence to sequences of the most popular animals the Loch Ness monster was thought to be

3' TGC CAC CCC GGA GGT GCC CTG TGA AGG CAT CTC ATC GAA AGA CAA 5' Lake Sturgen

Earth BioGenome Project

A 'moonshot' for biology that aims to sequence, catalogue, and characterise the genomes of all of Earth's eukaryotic biodiversity over a period of 10 years

Genome-wide association studies

A large-scale analysis of the genomes of many people having a certain phenotype or disease, with the aim of finding genetic markers that correlate with that phenotype or disease.

implications of the Hardy-Weinberg (HW) Law

A population cannot evolve when it is in HW equilibrium - Sexual reproduction alone is not enough to drive evolution — are you surprised? - Other processes—like mutation, migration, genetic drift, or selection—are needed When in HW equilibrium, then this indicates that the population might be like a random-mating model in population genetics • Otherwise, some of the model's assumptions may be violated by the data (e.g., migration, non- random mating, and natural selection might have occurred) A single generation of random mating will restore HW equilibrium • HW equilibrium does not preclude that mutation, selection, migration, and genetic drift might be occurring. Different processes might interact and affect different genotypes differently

autophagy

A process in which lysosomes decompose damaged organelles to reuse their organic monomers

Single-nucleotide polymorphisms

A site in the genome where individual members of a species differ in a single base pair - 90% of human genetic variations result from SNPs and over 4,000,000 SNPs are found in genes - These SNPs are an important source of individual variation however, they can cause a myriad of inherited diseases - One of the grand challenges of molecular biology is to ascertain which SNP is pathogenic and which SNP is benign - bad SNPs removed, good ones stay

in situ hybridization

A technique using nucleic acid hybridization with a labeled probe to detect the location of a specific mRNA in an intact organism.

Monophyletic group

A valid clade is monophyletic, signifying that it consists of the ancestor species and all its descendants

Reverse transcriptase

An enzyme encoded by some certain viruses (retroviruses) that uses RNA as a template for DNA synthesis.

Mutation rate

An important property that informs us about the rate of evolution of different types of mutations - Measured using different metrics (e.g., per replication, per cell division, per gamete, etc) - Different factors affect the mutation rate (The type of mutation, The location of mutation in the genome (e.g., recombinational hotspots and mutational hotspots), The probability of detection of a mutation, The probability of repairing a mutation, Changes in natural selection (Darwinian selection vs. positive selection)) - Genomes evolve at different rates (chloroplasts < nuclear < mitochondrial) - Mutation rates are important properties of genetic data, allowing us to gain a better understanding of how fast different types of genes or gene products have evolved - When studying evolution of species, we often assume that nucleotide substitutions occurred at a steady rate, and then infer the divergence dates of different species

Paraphyletic group

Aparaphyletic grouping consists of an ancestral species and some, but not all, of the descendants

Polyphyletic group

Apolyphyletic grouping consists of various species with different ancestors

The Hardy-Weinberg Law

Assume the standard random-mating model in population genetics: - A large population of a diploid species - Sexual reproduction and random mating - Equal allele frequencies in the two sexes - Non-overlapping generations - No migration, no mutation, and no selection The Hardy-Weinberg Law then predicts that: - Allelic frequencies will remain the same, from generation to generation - Relative genotype frequencies will stabilise after one generation (i.e., the population will be in Hardy-Weinberg equilibrium)

National Apiculture Programme

Better bees in Ireland: identifying stressors and assisting beekeepers - To assist beekeepers in their work and transfer knowledge of the project - To combat beehive invaders and diseases, particularly Varroa - Collect information on colony losses, and investigate reasons for those losses o all major honey bee pathogens o determining pesticide and agrochemical levels in colonies o Investigate adaptation to a changing climate in the main honey bee groups/subspecies in Ireland (measure temp, humidity, foraging behavior) - Results of the national monitoring surveys will be analysed with the colony loss data - These analyses will enable us to determine which stressors or combination of stressors are likely contributing to colony loss in Ireland and more generally

Rhinolophus ferrumequinum

Bristol, England - Sample Size N = 160, Age Range 0-24 MLS: 31yrs Dr. Roger Ransome and Prof. Gareth Jones University of Bristol

Myotis myotis

Brittany, France - sample size 239, Age Range, 0-6+ MLS: 37yrs Bretagne Vivante

Given- a phylogenetic tree- branch lengths- a time estimate forone (or more) node

Can we date other nodes in the tree? • Yes... But ONLY if the rate of molecular change is constant across all branches

What is Conservation Genetics?

Conservation Biology + Genetics = Conservation Genetics - Preserving the information contained in species, if species go extinct they never come back - Assessing the conservation status of species/populations by their genetic characteristics - For instance, continuous homogeneous populations of a species are considered less important than isolated genetically distinct populations

hardy-weinburg in practice

Consider two autosomal loci, each with two alleles, one with 𝑅 and 𝑟, and the other with 𝑆 and 𝑇. Let 𝑝=𝑓 (𝑅) =𝑓 ()𝑆 and 𝑞=1−𝑝: - aka p is the frequency of the R allele, and Q is for r next gen genotypes = 𝑓′𝑅𝑅 =𝑝^2 𝑓′𝑅𝑟 =2𝑝𝑞 𝑓′𝑟𝑟 =𝑝^2 - in punnet square = multiple frequencies to get frequency of next generation genotypes

rough draft of the human genome

Craig Venter (left), president of Celera Genomics, and Francis Collins (right), director of the National Human Genome Research Institute, NIH, announce the completion of a rough draft of the human genome at a press conference in Washington, D.C., on June 26, 2000.

What process actually increases the number of genes in an organism's genome? A parsimony B mutation C cladistics D gene duplication E independent assortment

D gene duplication

dispersal vs migration

Dispersal - generally refers to the movement of individuals or propagules between discrete locations or populations Migration - refers to periodic movement to and from a specific geographic area - often seasonal and along a consistent route

Paralogous genes that have lost the function of coding for any functional gene product are known as "pseudogenes." Which of these is a valid prediction regarding the fate of pseudogenes over evolutionary time? A They will be transformed into orthologous genes. B They will be preserved by natural selection. C They will ultimately regain their original function. D They will be highly conserved. E They will have relatively high mutation rates.

E They will have relatively high mutation rates. - not under selective pressure

In which of these scenarios would you expect the greatest impact of genetic drift on differences in allele frequencies among a group of 10 populations?

Each population starts with a size of 20 and allele frequencies of p = 0.5 and q = 0.5

AGE IMMUNE: Hypothesis

Endogenous Stimulants. Adaptation of Immune System + Removal Cellular Damage + DNA Repair + Restoration to Homeostasis, Limiting "Garb-Aging", Unexpected Longevity, Tolerance of Pathogens

An organism has a genome that consists of 500 million bp, the density of genes varies across the genome, and a large fraction of the genome that consists of repetitive sequences derived from transposable elements. This genome is most likely from which organism? Please choose the correct answer from the following choices, and then select the submit answer button. Answer choices

Eukaryotic genomes vary in size, but they are larger than prokaryotic genomes, vary in their density of genes, and often contain many repetitive sequences

Bats: secret of extended healthspans

Grand Challenge 1: Healthy Ageing Grand Challenge 2: Infectious Disease - Recall that nature—in the guise of certain animals such as birds, bats, and mole-rats—has repeatedly discovered how to deal with damaging free radicals much better than humans can. Other species (like elephants and whales) have developed dramatically better cancer resistance than humans...........At some point, I am confident, the full armamentarium of the biomedical research enterprise will be deployed to study and eventually understand these lessons nature has to teach us about preserving and prolonging health

Myotis bechsteinni

Greifswald, Germany - Sample Size N = 44, Age Range 1-16 MLS: 21yrs Prof. Gerald Kerth University of Greifswald

Pete is working on creating a cDNA library for a new bacterial species that has been discovered. After he completes the process, he notices that the resulting library contains all the genes present from the original, isolated DNA sequence. After evaluating the steps shown, where did he make his first mistake in the process?

He extracted all of the RNA molecules from the cell. Only mRNA should be isolated in order to be copied into cDNA. The production of cDNA is to complement mRNA.

population genetics

How do we describe and analyse genetic material from populations of sexually reproducing, interbreeding individuals (e.g., humans, peas, fish, oysters, etc)? • We use population genetic markers and methods What is population genetics? • It is a scientific discipline that studies the gene pools (i.e., shared set of genes) of sexually-reproducing, interbreeding populations of individuals (i.e., a Mendelian population)

Important factors for population genetics of small and isolated populations

I. Genetic Drift II. Inbreeding III. Gene Flow - effective population size versus actual number of individuals

Which of these correctly puts the steps of map-based approaches to whole-genome sequencing in the correct order? I: A subset of overlapping clones that efficiently cover the entire chromosome are selected and fractured, and the pieces are then cloned. II: Partial digestion of DNA resulting in overlapping fragments that are then cloned in bacteria. III: The large-insert clones to be assembled into a contig. IV: Each of the small-insert clones are sequenced, and overlap in sequences is used to assemble them in the correct order

II, III, I, IV In map-based sequencing, short sequenced fragments are assembled into a whole-genome sequence by first creating detailed genetic and physical maps of the genome, which provide known locations of genetic markers, which are later used to help align the short, sequenced fragments in their correct order

affinity capture

In affinity capture, an antibody to a specific protein is used to capture one protein from a complex mixture of proteins

Phylogenetic Trees with Proportional Branch Lengths

In some trees, the length of a branch can reflect the number of genetic changes that have taken place in a particular DNA sequence in that lineage - In other trees, branch length can represent chronological time, and branching points can be determined from the fossil record

Inbreeding Depression

Inbreeding reduces reproduction and survival in essentially all well studied outbreeding species and to a lesser extent in selfing species - dominance - heterozygote advantage - Outcrossing reverses the deleterious effects of inbreeding

HW Summed Up

Introduced the Hardy-Weinberg Law and saw how it allows us to study populations Initially, we assumed: - A large population of diploid, sexually-reproducing individuals - Non-overlapping generations, Mendelian formation of gametes, and random mating - No mutations, no migration and no natural selection Given these assumptions, the Hardy-Weinberg Law predicts that: - The relative allele frequencies will remain the same across generations - The relative genotype frequencies will reach equilibrium after one generation The implications of the Hardy-Weinberg Law are that: - A population that is in Hardy-Weinberg equilibrium cannot evolve - Sexual reproduction is not enough to drive evolution - Other evolutionary processes are required to drive evolution

What did the HapMap Project accomplish?

It cataloged and mapped SNPs and other human genetic variants that could be used to identify common haplotypes in human populations.

positional cloning

Method that allows for the isolation and identification of a gene by examining the cosegregation of a phenotype with previously mapped genetic markers.

Categories of mutations

Mutations may occur in - Somatic DNA (DNA that does not end up as gametic DNA), Affects some cells (may lead to mosaic tissue), The cause of many non-hereditary diseases (e.g., many types of cancer) - Germline DNA (DNA that ends up as gametic DNA) Will affect all cells (will not lead to mosaic tissue), The cause of hereditary diseases (e.g., dominant cystic renal disease) The cause of ABO, Rh+/Rh-, MN blood groups The cause of novel enzyme functions

Is having a very stable nest temperature important?

Neurological effects? Physical effects? - physical = Fluctuating asymmetry, A measure of developmental stress, not affected based on rearing temp - neurological - effects how bees learn, affected based on rearing temp, esp. short term memory developmental stability is not affected by rearing temperature, but possibly greater learning and memory abilities

Nonstandard base pairing

Nonstandard base pairing might occur due to the flexibility in DNA structure

Migration Equation Notation

Notation 𝑞I allele frequency in population I 𝑞II allele frequency in population II 𝑞I' new allele frequency in population II 𝑚 proportion of migrants Δ𝑞 change in frequency of allele 𝑎 New allele frequency 𝑞I' =𝑞I𝑚+𝑞II(1−𝑚) Change in allele frequency Δ𝑞=𝑞I' −𝑞II Δ𝑞 = 𝑚(𝑞I − 𝑞II)

Mutation Equation Notation

Notation 𝜇 rate of forward mutations 𝜐 rate of reverse mutations Δ𝑞 change in frequency of G^2 (mutated gene) Δ𝑞 = 𝜇𝑝 − 𝜈𝑞 At equilibrium, Δ𝑞 = 0, so 𝑝=𝜐/(𝜇+𝜐) 𝜐/𝜇=𝑝/(1−𝑝)

Natural selection

Occurs when the fitness (𝑊) varies across the genotypes (0 ≤ 𝑊 ≤ 1) - Acts at the phenotypic level, and may change the relative frequencies of genotypes and alleles, from gen to gen ( average fitness equation) - Depending on the fitness values, genetic diversity may be maintained or reduced - Natural selection is often quantified using a selection coefficient (s), which measures the relative intensity of selection against a genotype(𝑠=1− 𝑊) - Different types of fitness scenarios are possible and have different implications

Shared characters are used to construct phylogenetic trees

Once homologous characters have been identified, they can be used to infer a phylogeny

Identify the specified genes as orthologs or paralogs.

Orthologs: -A1 in species 1 and A1 in species 2 -A1 in species 2 and A2 in species 3 -A1 and B1 -all copies of A2 -A1 and B2 Paralogs: -B1 and B2 -A1 and A2 in species 2

Within the same gene pool, .................... genes can diverge from each other.

Paralogous - having an extra copy of a gene permits modifications to the copy without loss of the original gene product. - orthologous genes diverge post speciation

qPCR Assay

Principle: Measure the ratio of telomere sequence (T) relative to a single copy gene (SCG). - long telemore appears after less PCR cycles

Genetic drift

Remember, we assumed:... - Occurs when populations are small and uniting gametes do not reflect the previous generation's gene pool (i.o.w., there is sampling error) - Leads to stochastic changes in allele frequencies across generations - May lead to loss of alleles in a population and, hence, to loss of genetic diversity - May lead to divergence among populations (or sub-populations) - Is linked to founder effects and genetic bottlenecks - The magnitude of genetic drift is inversely proportional to population size

strand slippage

Slipping of the template and newly synthesized strands in replication in which one of the strands loops out from the other and nucleotides are inserted or deleted on the newly synthesized strand. - Insertions and deletions may result from strand slippage - Unequal crossing-over yields insertions and deletions

alleles

Strictly speaking, alleles are physical variants of the same genetic material (i.e., usually a gene) found at the same locus (i.e., position on a chromosome that is occupied by the allele) - Silent alleles (a.k.a. null alleles; here denoted by •) - Expressed alleles (Co-dominant alleles (here denoted by R, S), Dominant-recessive alleles (here denoted by R, r) - Example — A 4-allele locus (S, R, r, •) in a diploid species - homozygotes = SS, RR, rr, ••

Jordan is studying the process of genome editing utilizing the CRISPR-Cas system in a bacterium. She designs a viral marker that can inhibit the transcription of CRISPR RNA in response to a specific strain of viral DNA. If that virus is introduced, which of these statements can Jordan conclude concerning the utility of the CRISPR-Cas system? Please choose the correct answer from the following choices, and then select the submit answer button. Answer choices

The Cas protein will not be able to induce any activity as it cannot bind to form effector molecules. The formation of the complex is dependent on the transcription of CRISPR RNA. If the RNA molecule is not created, the action of the Cas protein would not help as it needs to recognize the foreign DNA through its complementary product. Challenge

Bat Mitochondria

The Free Radical Theory of Ageing - Repair or remove the damage? - Bat Blood- Anti-ageing gene expression? - Bats increase the maintenance of their DNA as they age - Bats show similar expression with age of genes known to extend life span in model organisms

interactome

The set of protein-to-protein interactions that occurs in a cell.

haplotype

The specific set of SNPs and other genetic variants observed on a single chromosome or part of a chromosome is called a haplotype

Miniopterus schreibersii

Tomar, Portugal - sample size 45, Age Range 0-17+ MLS: 22YRS Dr. Hugo Rebelo and Dr. Luisa Rodrigues

inbreeding coefficient

Usually, inbreeding is quantified by an inbreeding coefficient 𝐹 (i.e., the probability that two alleles are identical by descent) 𝐹 = 0 —> the alleles are identical by chance 𝐹 = 1 —> the alleles are identical by descent (equation?) - When inbreeding occurs, proportion of: Homozygotes increases, Heterozygotes decreases - Over generations, inbreeding will change the composition of genotypes:

Linkage disequilibrium

When a pair of alleles from two loci are inherited together in the same gamete more/less often than random chance would expect

The pros and cons of mutations

Without mutations, we would not: Be alive (+) Be part of the extant biodiversity (+) Be able to follow how populations of species change and adapt to chancing circumstances (e.g., pathogens, climate change etc) (+) Be able to uncover how species evolved and adapted to new circumstances (e.g., geological changes, novel habitats and niches, etc) (+) Have to live with a long list of diseases and genetic disorders (-) Have to live with perfectly adapted pathogens and agricultural pests (-)

Wobble base pairing

Wobble base pairing leads to a replicated error

shared ancestral character

a character that originated in an ancestor of the taxon - A character can be both ancestral and derived, depending on the context

Comparative genomics

a field of biological research in which the genomic features of different organisms are compared. - Enables us to understand how our own genome functions and how we evolved

Darwin Tree of Life Project

aims to sequence 70,000 eukaryotes in Britain and Ireland

Fins of fish and flippers of whales are the example of

analogous structures

Molecular phylogenetics

applies a combination of molecular and statistical techniques to infer evolutionary relationships among organisms or genes

Maximum parsimony

assumes that the tree that requires the fewest evolutionary events (appearances of shared derived characters) is the most likely

Which of these is required for mapping restriction sites (restriction mapping)?

calculation of recombination frequencies between restriction sites sequencing the DNA that encompasses restriction sites subcloning overlapping fragments of DNA cut with restriction enzymes ***simultaneously cutting the DNA with two restriction enzymes (a double digest)

Targeted mutagenesis

can be used to produce mutations at specific sites in DNA, allowing genes to be tailored for a particular purpose

microRNAS regulation

can bind to complementary sequences on mRNA molecules either degrading the target mRNA or blocking its translation

A geneticist inserts a DNA fragment into a restriction site within the lacZ gene of a plasmid that also has an ampicillin-resistance gene. The geneticist then transforms lacZ− bacterial cells with the plasmids and plates the bacteria on a medium containing ampicillin. Which cells will have copies of the recombinant plasmid?

cells that grow and are white, because they did not produce β-galactosidase The cells that grow and remain white have a plasmid in which the inserted DNA fragment has disrupted the functional lacZ gene.

A set of overlapping DNA fragments that form a continuous stretch of DNA is a

contig

Covid molecular clock

covid 2 diverged from ancestor RaTG13 40-70 years ago

What is the first step in map-based sequencing?

creating detailed genetic and physical maps

reporter sequence

encoding an easily observed product used to track the expression of a gene of interest

Methods have been developed for isolating and sequencing RNA from single cells (termed single-cell RNA sequencing or scRNA-seq). All of these are examples of this process EXCEPT

examining the expression patterns of genes from primary tumors of women who had breast cancer. This example demonstrates the use of a microarray.

Endogenized viruses

family of viruses within our genome with similarities to present day exogenous retroviruses. HERVs have been inherited by successive generations and it is possible that some have conferred biological benefits

Directional selection

favors one allele over another and leads to fixation of the favored allele

Homologous

genes that are evolutionarily related

maximum likelihood

given certain rules about how DNA changes over time, a tree can be found that reflects the most likely sequence of evolutionary events

Which of these is NOT used in the process of a mutagenesis screen? SNPs radiation heat map transposable elements

heat map

Paralogs

homologous genes arising by duplication of a single gene in the same organism - two same genes in one organism - paralogous genes result from gene duplication, so are found in more than one copy in the genome - They can diverge within the clade that carries them and often evolve new functions

Orthologs

homologous genes in different species that evolved from the same gene in a common ancestor - different genes in dif species in same spot - Orthologous gene found in a single copy in the genome and are homologous between species - They can diverge only after speciation occurs

In bacteria, the CRISPR-Cas system is most like which human system?

immune system

Which of these statements is FALSE concerning the whole genome shotgun sequencing? The small-insert clones are synthesized from the entire genome at one time. The organization of the clones is based on its overlapping sequences. The proposal of the whole-genome shotgun approach was suggested to be quicker in its sequencing than the application of the map-based approach employed by the International Human Genome Sequencing Consortium. The use of shotgun sequencing was initially for the assembly of smaller genomes, such as with bacteria.

third one

With RNA sequencing, this approach provides detailed information about gene expression, including all of these EXCEPT:

to examine the expression of microRNAs (miRNAs) in human cancers

Which components make up the CRISPR-Cas genome editing?

tracrRNA, crRNA, and Cas9

Whole-genome shotgun sequencing

uses sequence overlap to align sequenced fragments.

Dom-Recess or Co-Dom Relative allele frequencies Part 2

𝑝=𝑓 (𝑅) =𝑓 (𝑅𝑅) +(𝑓 𝑅𝑆 +𝑓 𝑅𝑇)/2