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SHI Meng

SHI Meng. Abstract.

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SHI Meng

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  1. SHI Meng

  2. Abstract • Changes in gene expression are thought to underlie many of the phenotypic differences between species. However, large-scale analyses of gene expression evolution were until recently prevented by technological limitations. Here we report the sequencing of polyadenylated RNA from six organs across ten species that represent all major mammalian lineages (placentals,marsupials and monotremes) and birds (the evolutionary outgroup),with the goal of understanding the dynamics ofmammalian transcriptome evolution.We show that the rate of gene expression evolution varies among organs, lineages and chromosomes, owing to differences in selective pressures: transcriptome change was slow in nervous tissues and rapid in testes, slower in rodents than in apes and monotremes, and rapid for the X chromosome right after its formation.Although gene expression evolution inmammalswas strongly shaped by purifying selection,we identify numerous potentially selectively driven expression switches, which occurred at different rates across lineages and tissues and which probably contributed to the specific organ biology of various mammals.

  3. Background • Regulatory mutations affecting gene expression probably explain many or even most phenotypic differences between species • RNA-seq protocols now allows for accurate and sensitive assessments of expression levels

  4. Data • RNA-seq data • 3.2 billion Illumina Genome Analyser IIx reads of 76 base pairs • Tissues: • fraction of brain, cerebellum, heart, kidney, liver and testis • Species: • placental mammals: great apes, including humans; rhesus macaque; mouse • marsupials: grey short-tailed opossum • monotremes: platypus • bird: red jungle fowl

  5. Procedure • refined existing Ensembl genome annotations • remapped RNA-seq reads and resolved read mapping ambiguities • comparative analyses of expression levels of protein-coding genes

  6. RNA-seq and genome reannotation • modified boundaries for 31,000–44,500 exons • 20,000–34,500 new exons • 66,000–125,000 new splice junctions • thousands of multi-exonic transcribed loci • lower levels and significantly less conserved

  7. RNA-seq and genome reannotation • 11–30% of the total genomic length is covered by unambiguously mapped RNA-seq reads • 34–61% of amniote genomes are transcribed • ten amniote species: 5,636 1:1 orthologues • six primates: 13,277 1:1 orthologues

  8. Mammalian gene expression phylogenies

  9. Mammalian gene expression phylogenies • Neighbour-joining trees • distance: 1-ρ(Spearman’s correlation coefficient)

  10. Mammalian gene expression phylogenies • Primate expression phylogenies

  11. Rates of expression change in lineages and organs • The branch lengths from the common ancestor of all species to the tips of the tree are remarkably similar • the branches leading to mouse are significantly shorter in several tissues: strong purifying selection • total branch lengths of the trees vary widely among tissues

  12. Gene expression evolution on the X chromosome • compared rates of expression change for genes that are X-linked in both eutherians and marsupials and autosomal genes • in the common ancestor of therian mammals: faster on the X chromosome • more recently: similar to that of autosomes

  13. Modular gene expression change • Modular: groups of genes that have coherent expression patterns over subsets of samples • 639 modules in the all-amniote data • 197 modules in the primate-specific data • 33 organ-specific modules with conserved expression levels among species • typical processes, define common primate/mammalian organ functions • 145 modules specific to an organ with distinct lineage-specific expression patterns • 25 nervous tissue modules

  14. Modular gene expression change • Internal branches of the mammalian phylogeny • 8 out of 32 modules in brain, cerebellumand/or testis are highly enriched with X-linked genes and became strongly down-regulated • Modular expression changes between mammals and chicken • neural tissues and in kidney and liver • 4 significantly enriched with X-linked genes • Humans only lineage with brain-specific expression modules in the primate data set • neuron insulation

  15. Modular gene expression change

  16. Expression shifts of individual genes • a maximum-likelihood framework for modelling gene expression evolution along a phylogeny • 9,255 significant expression changes • 63% tested amniote orthologues and 33% tested primate orthologues experienced at least one significant expression shift • the testis: largest number; the brain: few (except for the primate ancestral branch)

  17. Expression shifts of individual genes

  18. Conclusion • refines previous hypotheses • provides many new clues to the function and evolution of mammalian genomes • exploitation of the reported transcriptome data

  19. Thank you!

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