Jumping genes and aging: de novo transposable element insertions respond

to selection for time to developmentKate L. HertweckMira Han (NESCent)

Lee F. Greer (UC Irvine)Mark A. Phillips (UC Irvine)

Joseph L. Graves, Jr. (NC A&T, UNC Greensboro)Michael R. Rose (UC Irvine)

Twitter @k8hertGoogle+ k8hertweck@gmail.com

Blog: k8hert.blogspot.comwww.slideshare.net/katehertweck

Wikicommons

Transposable elements as a model system

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

● TEs, mobile genetic elements, or jumping genes

● Parasitic, self-replicating

● Similar to or derived from viruses

● Move independently in a genome

Class I: Retrotransposons(copy and paste)

LTRLINESINEERVSVA

Class II: DNA transposons(cut and paste)TIR (P elements)

MITECryptonHelitronMaverick

Genome-wide TE insertions and lifespan

Kate Hertweck, Genomic effects of repetitive DNAKate Hertweck, NESCent, Genomic effects of junk DNAK. Hertweck (@k8hert), NESCent, de novo TEs and time to development

Empirical data: it depends!

● TIR DNA transposons: decrease or have no effect on lifespan (Drosophila: Nikitin and Woodruff 1995; C. elegans: Egilmez and Reis 1994)

● LTR retrotransposons decrease lifespan (Drosophila: Driver and McKechnie 1992)

● Alu SINEs reverse senescence (human cell lines: Wang et al. 2011)

● TEs linked with epigenetic changes (Wilkins 2010, Baillie et al. 2011)

Theory: TE proliferation will decrease lifespan, accumulation of mutations (Kirkwood 1986, Murrey 1990)

What is the relationship between TE insertions and lifespan?

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

Rose laboratory Drosophila stocks

Long term experimental evolution systemEstablished 1980

A 9-day life cycleB 14-day life cycle (baseline)C 28-day life cycle

ACO

CO

BO

NCO AO

B

O

Original population

A, B, C derived twice eachReversal of selectionTesting for convergence

All populations replicated five times

Joe Graves, “Genome-wide convergence with repeated evolution in Drosophila melanogaster, Monday 10:30 305B (Experimental Evolution)

Experimental data

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

● Whole-genome resequencing (Illumina Hi-Seq)

120 females x six treatments x five replicates

● Are there areas of significant differentiation in the genome? Where? Hard vs. soft sweeps (Burke et al., 2010)?

SNP analysis: Popoolation2 (Kofler et al., 2011)

Known (ancestral) TE detection: Tlex (Fiston-Lavier et al. 2010)

Structural variant analysis: Delly (Rausch et al., 2012)

How do frequencies of known TE insertions respond to selective pressures?

How does total TE load respond to selective pressures?

Bioinformatics approach

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

● RelocaTE 1.0.4 (Robb et al. 2013)

● Uses TSD sequence motifs (LTR and TIR) and reference genome● 82 canonical sequences (Bergman, v.9.43) and Dmel v5● Filtered for read count >10 (custom)

● PoPoolationTE 1.02 (Kofler et al. 2012)

● Uses known insertions, reference genome, TE hierarchy● 5200 insertions from annotation 5.55● Filtered for read count >10

● Summarizing data

● Total TE insertions identified (by order)● Total TE families (by order)

RelocaTE: total TE insertions

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

CO NCOACO AO BO B

**

Populations of flies with short v long lifespan have significantly different numbers of total TEs (all C v all A: p=0.028*)

This difference appears to be driven by retrotransposons (shorter lifespan, more LTRs)

RelocaTE: total TE families

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

CO NCOACO AO BO B

No significant differences between treatments for number of TE families

What about other types of TEs?

PoPoolationTE: total TE insertions

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

CO NCOACO AO BO B

No significant differences between groups

What's the deal with replicate 5?

PoPoolationTE: total TE families

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

CO NCOACO AO BO B

PoPoolationTE more consistently IDs TE families

ACO

CO

BO

NCO AO

B

O

Original population

Conclusions

● RelocaTE is more conservative than PoPoolationTE in estimates of de novo TE insertions, but appears to miss some families

● Some evidence for more TEs associated with shorter lifespan, most variation in LTRs

● One population replicate presents a much different profile in overall TE load:

● Not apparent with all algorithms ● Multiple types of genomic responses to same selection?

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

Continuing work

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development

● Additional filtering and screening to determine exact specificity of de novo TE calls between algorithms

● Overlap between TE calls from different programs

● Genome-wide tests for significance of different genomic events (SNPs, structural variation, TEs)

● Testing for repeatability of evolution? What is up with replicate 5?

Acknowledgements

● Fellow NESCent scientists (for abiding my gluttonous shared computer cluster appetite)

● Casey Bergman and Michael Nelson (U Manchester)

● Joe Graves, “Genome-wide convergence with repeated evolution in Drosophila melanogaster, Monday 10:30 305B (Experimental Evolution)

Blog:k8hert.blogspot.comwww.slideshare.net/katehertweck

Twitter @k8hertGoogle+ k8hertweck@gmail.com

Variation in replicate 5 from sequencing coverage?

K. Hertweck (@k8hert), NESCent, de novo TEs and time to development