Evolution of Genes and Genomes in the Genus Drosophila
Introduction
 Model system for evolutionary genomics
o Use well-characterized model system to better understand genome
evolution
o Phylogeny imposes an extrinsic hypothesis for how features of the genome
should change.
o Take advantage of multiple species to study gain, loss, duplication and
transformation of genomic feature
o Optimize species choice and methods for comparative genomics
o Relate genome variation to phenotypic variation
 Background
o Species and phylogeny (Figure showing phylogeny and pictures of each
species – Teri Markow)
o Age of group
o Evolutionary history and ecological niches
o Characteristics of each species/species group
Results
 Overview of sequencing and assembly (Doug Smith)
o Sequencing (Doug Smith, summarizing results of Agencourt, JCVI, Wash
U, Broad)
 Not too much detail in the text, mostly in methods
 Differences between the projects (libraries, depth of coverage, etc)
o Assembly (Doug and Sergei)
 Reconciliation – need a graf on this since it’s not standard – then
point to paper on reconciliation process (Jim Yorke and
colleagues)
o Table summarizing sequencing stats for all species (will also be a
supplement with additional information) (Mike Eisen and Venky Iyer)
 Number of reads and total bases
 Genome size (not from sequence – do we have estimates of this? if
not, we will do these here)
 Assembly
 Contigs
 Scaffolds
 Size
 Coverage
 Genes
o Wolbachia (this is just a reference to the paper on discovering Wolbachia
in these traces)
o Maybe a note on mtDNA here too?
 Annotation
o Coding genes (Venky Iyer, Mike Eisen)
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Different methods used (Venky Iyer, Mike Eisen, Mike Brent,
Chris Ponting, Andreas Heger, Lior Pachter, Don Gilbert, NCBI,
others?)
 Consensus sets (Venky Iyer, Aaron Mackey)
 Problems with consensus sets
 Masking of alignments (Tim Sackton)
 Synteny (Venky Iyer, AJ Bhuktar)
o ncRNAs (Casey Bergman)
o tRNAs (Casey Bergman)
 Have RFAM annotations
 Have asked Ian Holmes to provide de novo annotations
o miRNAs (Chung-I Wu)
o Transposable elements (there are several groups who have tried to
characterize TEs in these different genomes, and, since there is no really
solid method yet, I think they should be encouraged to submit a
description of what they did and found)
Coding gene alignments (Venky Iyer, Tim Sackton)
Whole-genome alignments
o Mercator (need Lior Pachter and Colin Dewey to describe these and
provide some info on their quality)
o 12-way blastz alignments from UCSC (Angie Hinrichs)
Genome structure – (Thom Kaufman, Steve Schaeffer, AJ Bhutkar, Bill Gelbart,
others?)
o Transposition and chromosomal rearrangements
o Inversions
 Macro
 Micro
o Patterns of synteny
o Relating rates of evolution to rearrangements
Genome Size (Eisen Lab)
o Where is the variation in genome size coming from?
o What are the relative sizes of different features in different genome (e.g.
introns, utrs, intergenic space, other features)
o How are insertions and deletions of different sizes distributed across the
genomes?
o Are they expansions/losses
Coding gene evolution (Andy coordinating with lots of contribution from othersRasmus Nielsen, Melissa Hubisz, Montse Aguade, Julio Rozas, Mohamed Noor,
Lindy McBride, Roman Arguello, Chris Ponting, Andreas Heger )
o Rates
 dN/dS
 adjusted for codon useage/GC etc..
 amino acid sequence rates – radical vs. conservative across whole
taxa
 rate heterogeneity
o Relationship between rates and
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genome features
 GC
 recombination
 TE density
 gene properties
 GO
 expression
o Properties of
 extremely conserved genes
 rapidly diverging genes
 specific classes of genes
o Selection
 Positive selection
 Lineage specific positive selection
 Inference of selection stratified by functional class
 Sex related genes – Rama Singh, Mariana Wolfner
 Genes involved in speciation (Dan Barbash, Allen Orr,
Daven Presgraves)
o Codon usage (Severio Vacario, Jeff Powell, Akashi, Andreas Heger, Chris
Ponting)
o Selection at synonymous sites (Nielsen, Chip Aquadro)
o Gene structure evolution
 Intron/Exon structure (Scott xxx, Hartl)
 Splice signals (Angela Brooks and Michael Eisen)
 Promoters
Intron Evolution (Josep Cameron, Wolfgang Stephan, Dmitri Petrov, Scott Roy,
Dan Hartl, Andy Clark)
o Mechanisms for expansion and contraction
o Correlation with genome size
o Driven by indel balance or selection?
Multigene families (Matt Rasmussen)
o Expansion along different lineages
Specific families
o Innate Immunity (Andy Clark w/ Brian Lazzaro, Tim Sackton, Todd
Schlenke, Jay Evans, Dan Hultmark)
o Cytochrome P450s – Phil Batterham, Charles Robin
o OR/Gr – Roman Arguello, Lindy McBride
Novel/Lineage specific (Eisen)
o lineage specific genes
o lineage specific exons/introns
Genome organization
o Rearrangement
o Patterns of synteny
 Statistical model for this – do we have enough power?
 Rates of flux of genes onto and off of X chromosome
 Moving from arm to arm
o Genes moving between eu and heterochromatin
 RNA evolution (Casey Bergman)
 Regulatory sequence evolution (Mike Eisen, Dan Pollard)
o Binding sites
o Turnover
o Couple this with Kevin White and Brian Oliver’s evolution of gene
expression?
 Transposon evolution (Casey Bergman)
o Gain/loss
o Evolution of specific families
 age/history
 Comparison of rates and patterns of evolution in different genomic features
o e.g. Are genome rearrangments related to transposons positions? GC?
 Phylogeny
o Gene trees v. species trees (Dan Pollard – pointer to discordance paper)
o Species divergence times (Patrick O’Grady)
 What’s missing from D. melanogaster?
 Sections of genomic features
o X chromosome (Manyuan Long, Nadia Singh)
 Contrasting rates and patterns of divergence between X and
autosomes
 Codon usage differences
 Male-biased genes
 Male v. Female mutation rates
o Y chromosome (Bernardo Carvalho, Leonardo Koerich, Doris Bachtrog, ,
Amanda Larracuente, Andy Clark)
 Gene content, structure, organization
 Rates of gene gain and loss
 Rates and patterns of sequence divergence
o dot chromosome (Sally Elgin, Manyuan Long)
 Gene content, structure, patterns of divergence
 Traffic of genes onto and off of dot
 Polymorphisms
o Mitochondria (David Rand, Kristi Montooth, Dawn Abt, Jeffrey Hoffman)
 Assembly of mitochondrial genomes
 Analysis of divergence
 Gene phylogenies
Discussion points
 Benefits of having many species
 Species/Tree choice – depends on the question(s)
 Relationship between lineage specific biology and genomic features
 Analysis of genomes on a phylogeny provides an opportunity to ask questions at
the interface of full-genome biology and evolution:
o To what extent are genomic features driven by adaptive evolution as
opposed to being frozen accidents?
o To what extent do genomic features constrain the evolutionary options of
species?
o Are there genomic signatures of extinction liability?