Genome Biology: mornging session

Diverse growth tolerance

• Mimulus grows in both serpintine and non-serpintine soils
• focus today: also grows in toxic soils of abandoned mines
  • is this from new mutations developed since?
  • Bradshaw previously argued found tolerant indviduals from distant populations, so must be pre-existing
• focus on copper mines at copperopolis
• tolerant plants can grow roots in presence of copper — genetic basis with tolerance dominant mendilian.
• plants from the mines survive much better in copper mine soils.
• Cu tolerance locus explains most but not all of the variance
• Cu locus fell into a near-centromere region.
• find many examples of tolerance of sweeps occurring between mine and non-mine
• don’t find signal at Tol1 region of sweep
• core haplotype

ANdy Clark – Opssum genomic imprinting

• ~100 imprintd genes, ~20% are neuronal
• why give up diploidy?
• questions
  • how conserved are molecular mechanisms?
  • what are all the genes?
  • how do they get arise?
• examples:
  • H19 methylation difference – promoter silencing (methylated of allele silenced ?)
  • imprinting control region determines binding of CTCF between enhancer and IGF2 locus (methylated allele active ?)
• lot of variation of in which genes are imprinted across species
  • no imprinted genes in platypus, between marisupuls and other mammals
• Experiment
  • reciprical cross
  • RNA-seq and ChIPseq and methylation of extra embryonic tissue and embryonic tissue
  • ID SNPs and annotate expression.

findings

• major imprinted genes still imprinted
• Ube3a is imprinted in human and mouse but not in opossum
• new coding genes have differential methylation but noncoding do not
• methylation appears hemi-methylated by Pyro.
• marsups mostly inactive that paternal X. Small number of escapers — don’t overlap the eutherian mammal genes
• 8 eutherian mammal imprinted genes found imprinted in marsup.
• “collateral damage” expression of genes in introns of other genes affected in allele specific way by one of them acquiring imprinting.

Question

• What fraction of imprinting requirement is expression level,
  • recently acquired genes become lethal

Differences in patterns of recombination

• fly preferentially recombine near centromere, human near telomere, plant, away from centromere.
• birds do not have PRDM9
• compare recombination rates in zebra finch and long-tailed finch (similar to human to chimp divergence)
• zebrafinch and longtailed finch have more typical levels of nucleotide diversity — though many
• identify ‘hotspots’ of recombination
• most of the hotspots are shared between the species – 73% (close to detection level – possible all are shared)
• evidence of GC bias at hotspots
• hotspots appear to be conserved across greater genomic distances — unlike mammals.
• recombination peaks at transcription start sites. (genome acessable areas)
• birds do hybridize more readily — maybe this is related to the lack or recombination.

Di Rienzo – GWAS and ancestry of high altitude adaptation in tibetans

• Tibetas do not have the aclimatized Hb phenotype
• which physiological and genetic adaptations allow them to cope with low O2 (if not more Hb)
• regulators of hypoxia response: EPAS1 and EGLN1
• propose Tibetans are admixture of ancestral low-alt and ancestral high-alt, where sherpa are pure decedents of ancestral HA.
• second round of adaptation occurred after admixture
• cohort of ethnic Tibetans with SNP data (exome or genome?)
• find selective sweep at EP300, regulator of HIF1alpha
• EPAS1 gene also strong hit.
• also SLCO1A2 – invovled in heme turover. Heparin sulfate synthesis gene. and previously known EGLN1
• prominent role for transcriptional regulators
• no GWA association for Hb O2 – many true determinants do not reach genome wide signficance. in-signficant power despite sample size ~1000.
• Hb levels throughout lifespan is not the trait under selection (?)
• adaption in oxygen supply to fetus?
• both pregancies and live birth alleles in tibetians are signficantly enriched in Tibitans.
• Hb and Oxygen saturation linked genes show slight but insignificant increase among Tibitans.
• explanation of tradeoff — high Hb levels at high altitude increase blood viscosity leads to problems with pregancy and with strokes, heart disease etc.

Bachtrog

• Awesome but not tweetable: see protected post

Dowell (Carroll Lab): evolution of snake venom

• generating molecular novelity
  • duplication and new evolution
  • fusing of two ancestral poteins
• how frequently being used in other systems
• system: origin of snake venom
  • co-evolution of predator and prey. / adaptation co-variation
  • within species lots of variation.
• Western diamond-back rattlesnake venom: mostly metalloproteases and serine proteases. Also PLA2 (focus here)
• neurotoxic Pla2 heterodimer
• rattlesnake (Crotlids) phylogeny of non-neurotoxic, neurtoxicity prevelant on multiple branches. PLA2 on multiple scattered branches — likely ancestors had neurotoxic venomn, lost in many modern lineages.
• find other venom PLA2 genes mixed in with the locus of the dominant PLA genes in Mojhave rattlesnakes
• most of the transcription is just these two genes, not the near by PLA2s
• aligned locus to itself (duplication event?) — data supports 3(?) duplication events
• align to python genome, find locus but find only 1 bPla2 gene, not MtxA and B – no duplication event in this common ancestor.
• find orthogs in MtxB and MtxA in diamond back (here these are not the major used PLA2s) highly expressed with a key residue mutated. (Western D.R. not neurotoxic)

conclusions

• neurotoxic behavior is ancesteral and lost

Questions

• why lose? – larger snakes generally less neurotoxic, true in rattlesnakes
  • also correlated in scorpions, especially with strong hands, don’t need strong neurotoxin

Fu – an early modern human with recent Neandertal ancestor (Oase 1)

• 1-4% geneflow from Neandertal to modern human (not present in African humans)
• early modern human genomes, ~36 kya, and ~45 kya samples have neaderthals. Dated mixture ~50K yeears ago
• new ~37 Kyr human from ~Adriadic pennisula
• challenges: lots of microbe DNA, little degraded endogenous DNA, Fresh human DNA contamination.
• solution signature: cytosine deamination, C -> U read as T.
• mtDNS (more copies). 67% contamination, mostly from European. damage fragment much further back on lineage
• in solution capture (to replace shotgun), to get high efficiency recovery of nuclear DNA.
• equally close to pre-agriculture europeans and Asians, further away from modern european human / post-farming
• Oase 1 has 5-11% Neandertal (closer than modern).
  • also has larger contiguous chunks than others
  • estimate only 4 to 5 generations. Must have had admixture multiple times, not just ~50K years ago, also ~30-40K years ago.
  • this individual may be a decendent of both
• modern human Y does not have identified neandertal

Hilary Martin (Donnelly Group, oxford)

• 160 my divergence from other mammmals
• genome published in 2008: 21 autosomes, 10 sex chromosomes. Most scaffolds < 10 kb (error-prone), 20% seq assigned to chrom. No Y (seq female).
• scaffold with long mate apirs, BACs and fosmids. similar scaffold length but fewer errors
• Use GATK and CORTEX to call SNPs in individuals
• population structure (Tasmania clearly isolated on PC1). PC2 see split along NS axis.
• PRDM9 not likely to exist in paltypus.
• still have recombination hotspots (possibly an issue with genome assembly affecting LD estimates)
• some overlaps but a number of divergent hotspots of recombination — most in fact not shared.
• most hotspots not near TSS
• females 5 pairs of Xs, males 5 Xs 5 Ys
• fined evidence of recent combination between X and Y (still polymorophic within the individual river population)
• X onto Y recombination could be due to meiotic recombination or non-allelic homologous recombination mediated by flanking repeats. — transition of autosome to sex chromosome?