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SHI Meng
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.
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
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
Procedure
• refined existing Ensembl genome annotations
• remapped RNA-seq reads and resolved read
mapping ambiguities
• comparative analyses of expression levels of
protein-coding genes
RNA-seq and genome reannotation
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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
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
Mammalian gene expression phylogenies
Mammalian gene expression phylogenies
• Neighbour-joining trees
• distance: 1-ρ(Spearman’s correlation coefficient)
Mammalian gene expression phylogenies
• Primate expression phylogenies
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
Gene expression evolution on the X
chromosome
• compared rates of expression change for genes that are Xlinked 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
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
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
Modular gene expression change
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)
Expression shifts of individual genes
Conclusion
• refines previous hypotheses
• provides many new clues to the function and
evolution of mammalian genomes
• exploitation of the reported transcriptome data
Thank you!