LF263 Evolution L13-14
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LF263 Evolution L13-14 - Marcador
LF263 Evolution L13-14 - Detalles
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| Finding key genes | Differential gene expression of differently looking animals at the *same* stage, same cells. Gene expression list – verify by RNA ISH Verify gene function by misexpression or knockdown Assay: 1.How do genes found thus regulate each other? RNA ISH 2. Can we recover ancient morphologies or morphologies of related Species by changing gene expression during this same ontogenetic stage |
| Calmodulin Signalling pathways | Activated by Ca2+, activate CaMKII and CaN. CaN activated NFAT (TF). CALM activates CaMIV and CREB (TF) |
| Calmodulin CaM | Earlier: Levels and extent of Calmodulin expression in the upper beak correlates with upper beak shape/size across the Darwin finches. The more in the mesenchyme, the more pointed the beak! |
| BMP4 | Early BMP4 expression Correlates with deep and wide beak. Signalling pathway: Canonical (smads) and non-canonical (Ras Raf etc) |
| Premaxilla | Variation in expression of genes TGFbeta signalling (for depth and length not width). Wnt pathway (beta catenin). In upper beak Correlates with beak shape Differences. |
| Epistatic relationships during beak development. | Alk5 and DKK3 (for depth and length but not width) upregulates CaM, BMP4 does not. BMP4 overexpression downregulates Itself. Differential effects on bone and cartilage |
| FGF8 | To make the rostrum in Paleognathous and Neognathae |
| FGF inhibition | Affects the premaxilla and the palatine bone |
| Human Genome Project | Only 1.5% is protein coding Highly conserved non-protein coding elements Regulatory evolution is faster than protein coding gene evolution 15% of CNEs from 120-90 Mya evolved from transposons. Most of the euchromatic genome is transcribed at a low level |
| Long haplotypes at high frequency satisfy: | Derived alleles Differentiation between the three main human populations Alleles with known biological effects |
| SNPs freq shows the basis for Tibetan adaptation to altitude | EPAS1 is a transcription factor associated with hypoxia – linked to high erythrocyte count Han and Tibetan populations estimated to have diverged 2750 years ago (Fst = 0.026, fairly low differentiation) Fastest selective sweep identified to date |
| Four major loci have been identified | Microcephalin (MCPH) – brain development ASPM – brain development FOXP2 – speech development HAR1 – brain development |
| Microcephalin phylogeny | The phylogeny of microcephalin haplotypes is unusual ‘lopsided’ suggestive of introgression recently (~40,000 years ago) – matches up conveniently with modern human contact with Neanderthals Did we get our brains from Neanderthals? possible |
| ASPM | Abnormal spindle-like microcephaly associated. Very high frequency of one haplotype Big problem – no phenotype is associated with haplogroup D, - if there is selection we don’t know what it was for. Dangerous inferences: scientifically and sociologically |
| FOXP2 | Transcription factor forkhead box 2 Mutations at FOXP2 are associated with speech disorders in humans Two significant amino acid changes occur in humans, and virtually no variation in humans The derived gene also occurred in Neanderthals |
| Human accelerated regions (HARs) | Previous examples focused on amino acid changes A study scanned entire genome for phylogenetic branch lengths longer in humans compared to chimpanzee, rat and mouse 49 HARs identified, 96% were non-coding RNAs, 24% were adjacent to neurodevelopmental genes HAR1 most significant, involved in cortical development: 18 substitutions occurred where 0.27 expected |
| Gene duplication episodes in humans | Identified inparalogs humans vs mouse using Inparanoid. Compared potential human inparalogs with chimp sequences phylogenetic analysis for each hum/chimp set and removed all molecular clock violations and only retained topologies |
| The Neanderthal Genome | Allows us to see what is specifically ‘human’ rather than hominin Genome obtained from 3 bones from Vindija Suggests a divergence between humans and Neanderthal’s of 825, 000 years Only 78 derived nucleotides fixed in human lineage but ancestral in Neandertals. |
| Detection of selective sweeps | Identification of older blocks of genome that tend to be derived in human and ancestral in Neanderthal THADA strongest signal |