Evolution of Genes and Genomes in the Genus Drosophila

Introduction

n 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

n 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

n 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?

n Annotation

o Coding genes (Venky Iyer, Mike Eisen)

§ 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)

n Coding gene alignments (Venky Iyer, Tim Sackton)

n 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)

n 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

n 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

n Coding gene evolution (Andy coordinating with lots of contribution from others- Rasmus 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

§ 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

n 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?

n Multigene families (Matt Rasmussen)

o Expansion along different lineages

n 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

n Novel/Lineage specific (Eisen)

o lineage specific genes

o lineage specific exons/introns

n 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

n RNA evolution (Casey Bergman)

n 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?

n Transposon evolution (Casey Bergman)

o Gain/loss

o Evolution of specific families

§ age/history

n Comparison of rates and patterns of evolution in different genomic features

o e.g. Are genome rearrangments related to transposons positions? GC?

n Phylogeny

o Gene trees v. species trees (Dan Pollard – pointer to discordance paper)

o Species divergence times (Patrick O’Grady)

n What’s missing from D. melanogaster?

n 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

n Benefits of having many species

n Species/Tree choice – depends on the question(s)

n Relationship between lineage specific biology and genomic features

n 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?