The Cobweb of life revealed by Genome-Scale estimates of - PowerPoint Presentation

Slide1

The Cobweb of life revealed by Genome-Scale estimates of Horizontal Gene Transfer

Fan Ge, Li-San Wang, Junhyong Kim

Mourya VardhanSlide2

Outline Controversy : The extent of HGT affecting the core genealogical history

Examination of this controversy by assessing the extent among core orthologous genes A novel statistical method : To asses the extent of HGT based on comparisons of tree topologySlide3

IntroductionHorizontal gene transfer (HGT) refers to the transfer of genes between organisms in a manner other than traditional reproduction.

Whole genome analyses of different prokaryotes have been thought to indicate rampant HGTsThere is an on going debate over the estimation of HGT frequency and its impact on phylogenyInference of HGT from tree comparisons should be done under a proper statistical frameworkSlide4

Methodology to assess the extentNew method to explicitly test

for phylogenetic incongruence due to horizontal transfer versus statistical tree errorsUsed Clusters of Orthologous Groups (COG) from NCBI databases

Extracted most reliable COGs

Built gene tree for every COG and integrated to construct W-G tree

Comparisons of each gene tree with W-G tree to infer significant HGT

Augmented this method to pairwise comparisons of gene trees to detect conflictsSlide5
Slide6

High-Quality Gene Groups and the W-G TreeCOG database is built by redoing sequence comparisons over 43 genomes

This resulted in retention of 297 high quality COG entries out of 3852 To approximate the W-G tree, they used median tree

estimator

The estimate used boot strap values from bootstrap samplingSlide7
Slide8

Detection of HGT eventsBy comparison of estimated trees against other gene trees or against trees that represent the history of genomes, we infer HGTs

Discrepancy in the trees maybe caused due to HGT or other errorsDistance metrics are used to test discrepanciesThe paper explicitly asks if the discrepancies are caused by HGT events, as an additional precaution.Slide9

Comparison MetricsMaximum agreement subtree (

MAST) - If two trees differ by branches, they share common subtree, the bound on size of the shared subtree can be calculated using MASTSymmetric Difference (SD

) - Difference in the trees can be found by

this

metric Slide10

Interpretation of HGT events…Case 1:

If both MAST and SD are low, trees are most likely not differentCase 2: If both the metrics are large, can be either HGT events or errorsCase 3: But if they have large SD and low MAST values, it is most likely an HGT event.

Case 4:

Large MAST and low SD cannot occur due to algorithmic reasonsSlide11

SD and MAST scores for Gene Tree 1 and the W-G tree are 2

and 2, while

the

scores

for Gene Tree 2 and

the W-G

tree are 8 and

2Slide12

The Hypothesis Test

Hypothesis test Ɣ – difference of the two metricsComputed by generating null distribution by bootstrapping gene treesHGT was inferred when the observed Ɣ

was significant with the p-value below the

5% level

Simulation

studies applied to each

COG showed it detecting

HGT events

as follows, in

a COG tree using the 5% significance

HGT Events

Rates

1

53.8

2

70

3

77.3Slide13

ds

is the SD metricdm is the MAST metricm,n are the no. of branch splits

X is the no. of taxa

Used PAUP software to calculateSlide14

HGT Estimation via Comparisons between Each Gene Tree and the W-G Tree

Hypothesis Test was applied to each COGObservations showed that the test does not significantly vary with the p-valueAt 5% level, 33/297 (11.1%) COGs showed putative HGTsThese COGs are termed

hCOGsSlide15

The Relationship between Detecting COG entries with HGT and the

p-ValuesSlide16

HGT Estimation via Comparisons among Gene TreesProblem with comparing

the Gene tree and W-G tree is that the results are sensitive to the W-G treeCOG entries do not all share the same taxaIf

its

a

hCOG

, it should test differently for all the

comparisons

14,004 pairs

of gene trees that contained greater than or equal to

six shared taxa were compared

At 5% level

,

1,764/14,004 (

12.6%) pairs were

significantSlide17
Slide18

Identification of transferred branches in gene trees.

For each COG that tested positive for HGT events, transferred branches were found by exhaustive enumeration of possible subtree matchesSearched for all combinations

of branch

prunings

to find the ‘‘troublesome

’’ branches

If there’s only one way to prune to make the trees congruent, it is an HGT eventSlide19

Color

HGT Rates

Red

>4%

Yellow

3%–4%

Pink

2%–3%

Blue

1%–2%

Green

1%Slide20

References

Goddard W, Kubicka E, Kubicki G, McMorris FR (1994) The agreement metric for labeled binary trees. Math

Biosci

123: 215–226.

Robinson

DF,

Foulds

LR (1981) Comparison of phylogenetic trees.

Math

Biosci

53:

131–147

Conover WJ (1999) Practical nonparametric statistics, 3rd ed. New

York: Wiley

. 584 p

.

Eisen

JA (2000) Horizontal gene transfer among microbial genomes:

New insights

from complete genome analysis.

Curr

Opin

Genet Dev 10: 606–611Slide21

Thank You!