CP RMSCC 2133. 99. threshold for significance after correction for mult. testing. CP RMSCC 3700. CP RMSCC 1037. CP RMSCC 3488. CP CPA 0001. C. posadasii. 100. CP CPA 0020. 95. CP1. 100. CP RMSCC 1038. CPS2. 99. 99. CP CPA 0066. CI RMSCC 2394. C. immitis. 100. 73 kb cds
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threshold for significance after correction for mult. testing
CP RMSCC 3700
CP RMSCC 1037
CP RMSCC 3488
CP CPA 0001
CP CPA 0020
CP RMSCC 1038
CP CPA 0066
CI RMSCC 2394
73 kb cds
ML, HKY + G
CI RMSCC 3703
Natural SelectionMost genes exhibit purifying selection
Heterogeneity in Ci vs Cp Divergence
Isolate Coverage Size (Mb)
C. immitis RS 14.41X 28.9
C. immitis H538.4 3.41X 27.7
C. immitis RMSCC_2394 8.22X 28.8
C. immitis RMSCC_3703 3.17X 27.6
C. posadasii Silveira 5.23X 27.5
C. posadasii RMSCC_3488 8.52X 28.1
C. posadasii RMSCC_2133 6.69X 27.8
C. posadasii RMSCC_3700 3.58X 25.5
C. posadasii CPA_0001 3.09X 28.6
C. posadasii CPA_0020 3.42X 27.3
C. posadasii CPA_0066 3.34X 27.7
C. posadasii RMSCC_1037 3.41X 26.6
C. posadasii RMSCC_1038 3.00X 26.1
C. posadasii C735 8X (JCVI) 26.7
Neutrality Index (NI) measured for each gene using counts of divergent(D) vs. polymorphic(P) synonymous(S) & replacement(N) SNPs.
Divergence (as measured by Fst) is nearly complete along most of each chromosome (Fst=1), but there are regions of much lower differentiation.
Locally reduced genetic differentiation could be caused by introgression or incomplete lineage sorting.
Functional Enrichment in Positively Selected Genes
Reference Genome: C. immitis RS
Total Annotated Genes: 10,355
Total SNPs: 670,880
Desert Valley Fever Facts
Coalescent Analysis: Introgression Occurring
Coalescent method to test H0(incomplete lineage sorting)
Wakeley & Hey 1997:
1. Use data from multiple loci to infer population parameters.
2. Analytically derive coalescent expectations for relative incidence of shared polymorphisms between species, fixed differences, and exclusive polymorphisms within species.
3. For individual loci, compare Obs vs. Exp mutation counts assuming no introgression.
(Chi sq. test results to left; significant results indicate evidence of introgression.)
Incomplete lineage sorting
CONCLUSION: Over 700 genes show evidence of recent introgresssion.
Evidence of Immune-Mediated Selection
We have fully sequenced the genomes of 4 C. immitis isolates and 9 C. posadasii isolates, allowing us to explore regional variation in patterns of intraspecific diversity and interspecific divergence. These genome sequences, in combination with the C. posadasii C735 genome previously sequenced by JCVI, offer an excellent resource for improving our understanding of these dimorphic fungal pathogens, which are the etiological agent of coccidioidomycosis (Valley Fever). Through analysis of all 14 genomes we find that although C. immitis and C. posadasii nominally diverged at least 5 million years ago, extensive regions of their genomes exhibit evidence of recent gene flow even while the majority of the genome exhibits perfect genetic isolation. We explore the signal of natural selection across all genes in both species, and identify signals of positive selection in membrane or cell wall associated proteins. These selection signals may indicate that immune-mediated selection pressure from mammalian hosts is an important driver of Coccidioides evolution, and help to clarify the relative importance of the saprophytic vs. parasitic phases of the Coccidioides life cycle.
Daniel E. Neafsey1, Bridget Barker2, Garry T. Cole3, John Galgiani2, Matthew R. Henn1, ChiungYu Hung3, Theo Kirkland4, Scott Kroken2, Cody McMahan3, Marc Orbach2, Daniel Park1, Steve Rounsley2, Thomas J. Sharpton5, Jason E. Stajich5, John W. Taylor5, Emily Whiston5, Bruce W. Birren1
1Broad Institute of MIT and Harvard, Cambridge, MA, USA, ([email protected]). 2University of Arizona, Tucson, AZ, USA. 3University of Texas, San Antonio, TX, USA. 4University of California, San Diego, CA, USA. 5University of California at Berkeley, Berkeley, CA, USA.