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Social, Human and Ecological Genomes - Coggle Diagram

- - - - SEGREGATING SITES (S): no. of polymorphic sites observed in population
      - ALLELIC RICHNESS (A): average number of alleles per locus
      - EXPECTED HETEROZYGOSITY H): equal to the expected proportion of heterozygotes under HWE (for a biallelic site H=2pq)
    - - genetic drift is stronger in smaller populations - larger samples replicate prev. generations allele frequencies more closely --> genetic drift is weaker in larger populations --> examples of drift: founder effect and population bottleneck
      - population bottleneck = only small no. of offspring produced - can inflate the sampling error and thus increase genetic drift --> reduction in overall population size e.g. due to famine
      - founder effect = isolation of a small fraction of the population from a larger group
      - genetic diversity decreases w/distance from africa -> allelic richness in non-africans decreases with distance from ethiopia
        
        linguistic diversity decreases w/distance from africa -> number of phonemes (distinct units of sound that differentiate words) in language correlates positively w/size of its speaker population
      - isolation leads to genetic differentiation -. allele frequencies will diverge through continued mutation, drift and natural selection
        
        genetic distance: can refer to either : 1. evolutionary distance (time since divergence from last common ancestor), 2. observed degree of genetic differentiation between two samples/populations/species // length of line seperating two points is best way to measure
        
        simple measure of distance between individuals = proportion of alleles not shared // if two alleles match tehy are identical-by-state (IBS) - for each locus, we can count the number of alleles that are IBS: 1,0, 2
      - COMPARING POPULATIONS: F2 statistic is a measure of distance between two populations - for each locus, it takes the diff in allele frequencies and squares it - these values are summed across all loci and divided by number of loci considered
        
        Pairwise Distance: can construct trees representing population relationships -> are a bad fit for human populations due to continuous gene flow / genetic distance not easily related to evolutionary history ie mutation rates, population sizes / often constructed using SNPs w/MAF > 1% -> african populations may appear more similiar -> entire genome sequences should be used
      - positive selection increase the alleles frequency in population
  - - - LARGE RUN = RECENT INBREEDING / excess of short runs = past bottleneck
  - - - reconstructing proto-indo european myths and legends
        
        the smith and devil:
        
        slaying the serpant
        
        the horse twins
        
        the otherworld: you must journey across a river, guided by an old man, to reach the realm of the dead
- - - - selection exhausts genetic variation: chromosome w/ an adaptive mutation increases in frequency as its favoured by natural selection -> adaptive mutation is fixed and all variation is eliminated
      - comparing synonymous and non synonymous mutations
        
        can help us identity selection in coding regions of genome -> not all muatations in coding region chnage the DNA-protein translation -> Mutation in the 3rd nucleootide often has no effect but mutation in the first or second changes the protein (thus position reflects mutations under selection) -> seeing more mutations in the 1st, 2nd than 3rd, this suggests selection
      - detecting selection: selection generates unbalanced trees - inidcating differences in diversification rates -> trees carry info about the underlying evolutionary processes - asymmetric trees indicate selection has operated
      - using sequences to detect mutations is biased when trying to understand frequency and effect of mutations -> there is onky on e single copy of a new mutation, if its deleterious (can cause harm), selection will act against it
        
        selection can only act when there is genetic variation
        
        mutation accumulation experiments - to prevent selection from removing deletrious mutations the study organism is kept at a bottleneck (no variation = no selection)
      - distribution of mutational effects - there is bias towards smaller species w/fast generation times and those with smaller genomes e.g. e.coli and other viruses
        
        advantageous mutations are rare - many mutations have no effect and many are lethal
        
        to know the actual effect of a gene:
        
        Quantitative trait loci (QTL) - crosses between individuals creates recombinants - correlate the phenotype to the genotype
        
        genome wide association study: phenotyping and genotyping an entire population - correlate the phenotype to the genotype // not all variation is present in the crosses, limited number of recombination events - areas identified by QTL are often large conatining many genes - low resolution bu t high statistical power
        
        based on variation in whole populations - often requires more genetic markers on gene as individuals arent related - sensitive to population structure if samples form multiple populations used
    - - potentiation: e.coli could ahve had prerequisite mutations - acquistion of ability to grow on citrate more likely in immediate ancestors
      - actualisation: duplication created a fusion between anaerobic citrate transporter and kinase - citrate transporter now expressed in aerobic conditions
      - refinement: initially function was v weak and additional mutations increased the benefit - esp. extra copies of the new gene - increased protein production - increases in fitness
- - - - vaginal birth bacteria: bacteroides, bifidobacteria, lactobacilli, E.coli
      - c-section: increased skin associated microbes, eg staphylococcus spp
    - - breast fed: bifidobacteria (beneficial microbe) - decreases w/age - onset of health conditions as we age ; human milk oligosaccharides support gut colonisation by bifidobacteria - only bacteria that express genes encoding the necessary enzymes to utilise milk oligosaccharides
      - age 1 : weaning - transition from milk to solid food - more new bacteria introduced
  - - - siruption of microbiota leads to pathogrn overgrowth and infection -> antibiotic usage and clostridium difficile infection occurs if: low numbers in healthy adult, antibiotic treatment in hospital patients - increase in C. difficile and severe inflammation - patients more susceptible to cluster infection - after antibiotic usem numbers increase - inflammation of GI tract lining due to toxin production from C.difficile
      - use pf antibiotics can disrupt microbiota -> overgrowth and infection
    - - microbiome of fermented foods eg kimchi, sauerkraut, unpasteurized yoghurt: their microbes are lactic acid bacteria (LAB) - responsible for the taste in food - have their own microbiomes, rich in beneficial microbes
      - probiotics (good bugs) = any bacterium that when administarted in adequate amounts has health promoting effects - lactobacillus and bificobacterium - members of nromal GI flora , probiotic properties / supplements, dairy products eg activia,
        
        probiotic charcteristics: nonpathogenic and nontoxic, human origin, resist gastric acid and bile, attach to epithelial cells, temporarily colonises intestinal tract, adapts to native intestinal flora // uses: IBS, infectious diarrhea
      - FMT: intestinal microbioat transferred from healthy donor to patient to restore stable microbial community for gut - restablishes a balanced microbiota - delivered via colonoscopy
  - - - associated w/high living standard and hygiene levels / linked to lack of breast feeding and a high sucrose, animal fat diet / associated w/antibiotic use
    - - therapeutic manipulations: fecal microbial transplant / probiotics - prevent dysbiosis
        
        probiotic mechanisms in IBD - enhanced barrier integrity: increased mucus secretion and enhanced tight juntions, antimicrobial activity, stimulation of immune response ie increase SIgA, competitive exclusion of bacterial adhesion/translocation, immunomodulatory actions: induce t cells, induce t cell apoptosis, dendritic cell modulation