We recently published the first genomic diversity study of Trypanosoma congolense, a major aetiological agent of Animal African Trypanosomiasis. We demonstrated striking levels of SNP and indel diversity in the Eastern province of Zambia as a consequence of hybridization between divergent trypanosome lineages. We concluded that these and earlier findings in T. congolense challenge the predominant clonal evolution (PCE) model. In a recent comment, Tibayrenc and Ayala claim that there are many features in T. congolense supporting their theory of clonality. While we can follow the reasoning of the authors, we also identify major limitations in their theory and interpretations that resulted in incorrect conclusions. First, we argue that each T. congolense subgroup should be analysed independently as they may represent different (sub)species rather than "near-clades". Second, the authors neglect major findings of two robust population genetic studies on Savannah T. congolense that provide clear evidence of frequent recombination. Third, we reveal additional events of introgressive hybridization in T. congolense by analysing the maxicircle coding region using next-generation sequencing analyses. At last, we pinpoint two important misinterpretations by the authors and show that there are no spatially and temporally widespread clones in T. congolense. We stand by our earlier conclusions that the clonal framework is unlikely to accurately model the population structure of T. congolense. Other theoretical frameworks such as Maynard Smith's epidemic model may better represent the complex ancestry seen in T. congolense, where clones delimited in space and time arise against a background of recombination.

In this study we investigated the association of ACAN variants with otosclerosis, a frequent cause of hearing loss among young adults.We sequenced the coding, 5'-UTR and 3'-UTR regions of ACAN in 1497 unrelated otosclerosis cases and 1437 matched controls from six different subpopulations. The association between variants in ACAN and the disease risk was tested through single variant and gene-based association tests.After correction for multiple testing, 14 variants were significantly associated with otosclerosis, ten of which represented independent association signals. Eight variants showed a consistent association across all subpopulations. Allelic odds ratios of the variants identified four predisposing and ten protective variants. Gene-based tests showed association of very rare variants in the 3'-UTR with the phenotype.The associated exonic variants are all located in the CS domain of ACAN and include both protective and predisposing variants with a broad spectrum of effect sizes and population frequencies. This includes variants with a strong effect size and low frequency, typical for monogenic diseases, to low effect size variants with high frequency, characteristic for common complex traits. This single-gene allelic spectrum with both protective and predisposing alleles is unique in the field of complex 4 diseases. In conclusion, these findings are a significant advancement to the understanding of the etiology of otosclerosis.

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