Many globally isolated AD hybrid strains of Cryptococcus neoformans originated in Africa.
Interspecific and intervarietal hybridization may contribute to the biological diversity of fungal populations. Cryptococcus neoformans is a pathogenic yeast and the most common fungal cause of meningitis in patients with AIDS. Most patients are infected with either of the two varieties of C. neoformans, designated as serotype A (C. neoformans var. grubii) or serotype D (C. neoformans var. neoformans). In addition, serotype AD strains, which are hybrids of these two varieties, are commonly isolated from clinical and environmental samples. While most isolates of serotype A and serotype D are haploid, AD strains are diploid or aneuploid, and contain two sets of chromosomes and two mating type alleles, MATa and MATalpha, one from each of the serotypes. The global population of serotype A is dominated by isolates with the MATalpha mating type (Aalpha); however, about half of the globally analyzed AD strains possess the extremely rare serotype A MATa allele (Aa). We previously described an unusual population of serotype A in Botswana, in which 25% of the strains contain the rare MATa allele. Here we utilized two methods, phylogenetic analysis of three genes and genotyping by scoring amplified fragment length polymorphisms, and discovered that AD hybrid strains possessing the rare serotype A MATa allele (genotype AaDalpha) cluster with isolates of serotype A from Botswana, whereas AD hybrids that possess the MATalpha serotype A allele (AalphaDa and AalphaDalpha) cluster with cosmopolitan isolates of serotype A. We also determined that AD hybrid strains are more resistant to UV irradiation than haploid serotype A strains from Botswana. These findings support two hypotheses: (i) AaDalpha strains originated in sub-Saharan Africa from a cross between strains of serotypes A and D; and (ii) this fusion produced hybrid strains with increased fitness, enabling the Botswanan serotype A MATa genome, which is otherwise geographically restricted, to survive, emigrate, and propagate throughout the world.
Litvintseva
Anastasia P
AP
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America. litvi001@mc.duke.edu
Lin
Xiaorong
X
Templeton
Irka
I
Heitman
Joseph
J
Mitchell
Thomas G
TG
D000349:Africa; D000782:Aneuploidy; D001483:Base Sequence; D003455:Cryptococcus neoformans / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D004271:DNA, Fungal / Q000032:analysis; D019143:Evolution, Molecular; D005800:Genes, Fungal; D049770:Genes, Mating Type, Fungal; D014644:Genetic Variation; D006801:Humans; D006823:Hybrid Vigor; D006824:Hybridization, Genetic; D016921:Meningitis, Fungal / Q000382:microbiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012703:Serotyping
D004271:DNA, Fungal
J Clin Microbiol. 2004 Dec;42(12):5624-35
15583292
Mol Ecol. 2000 Oct;9(10):1471-81
11050543
J Clin Microbiol. 2002 Mar;40(3):965-72
11880424
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14455-60
11121047
Fungal Genet Biol. 2000 Oct;31(1):21-32
11118132
PLoS Med. 2007 Feb;4(2):e21
17284154
Infect Immun. 2001 Jan;69(1):115-22
11119496
Trends Ecol Evol. 2004 Apr;19(4):198-207
16701254
Annu Rev Phytopathol. 2005;43:279-308
16078886
FEMS Yeast Res. 2006 Jun;6(4):574-87
16696653
Fungal Genet Biol. 1999 Jun;27(1):36-48
10413613
J Clin Microbiol. 2005 Feb;43(2):556-64
15695645
Emerg Infect Dis. 2003 Sep;9(9):1179-80
14528882
Mol Ecol. 2003 Nov;12(11):2861-73
14629368
Infect Immun. 1992 Mar;60(3):1101-8
1541525
Folia Primatol (Basel). 1989;53(1-4):190-202
2606395
J Med Vet Mycol. 1992;30(1):61-9
1573522
Microbiology. 2003 Aug;149(Pt 8):2147-54
12904554
Appl Environ Microbiol. 1994 Oct;60(10):3864-6
7986054
Eukaryot Cell. 2007 Jun;6(6):949-59
17449657
FEMS Yeast Res. 2006 Jun;6(4):608-13
16696656
Mol Ecol. 2004 Jun;13(6):1455-67
15140090
Annu Rev Microbiol. 2006;60:69-105
16704346
Infect Immun. 1999 Oct;67(10):5477-9
10496933
Trends Ecol Evol. 1995 Feb;10(2):67-71
21236955
J Med Vet Mycol. 1996 Sep-Oct;34(5):299-301
8912162
J Clin Microbiol. 2001 Nov;39(11):3889-94
11682503
Nihon Ishinkin Gakkai Zasshi. 2003;44(4):293-7
14615796
Mol Biol Evol. 2006 Oct;23(10):1879-90
16870684
Mycol Res. 2004 Oct;108(Pt 10):1172-84
15535068
Nature. 2005 Apr 21;434(7036):1017-21
15846346
Antimicrob Agents Chemother. 1996 Mar;40(3):541-5
8851567
Eukaryot Cell. 2003 Dec;2(6):1162-8
14665451
Med Mycol. 2001 Oct;39(5):383-6
12054047
PLoS Biol. 2005 Apr;3(4):e95
15760278
Infect Immun. 2003 Sep;71(9):4831-41
12933823
Mol Ecol. 2006 Jan;15(1):249-62
16367844
Nature. 2000 May 11;405(6783):134-5
10821256
Microbiology. 2002 Jan;148(Pt 1):203-12
11782512
Bioinformatics. 2001 Aug;17(8):754-5
11524383
Genetics. 2006 Apr;172(4):2223-38
16322524
PLoS One. 2007;2(5):e457
17520016
Science. 2005 Feb 25;307(5713):1321-4
15653466