Genetic diversity of laboratory strains and implications for research: The case of Aedes aegypti.

The yellow fever mosquito (Aedes aegypti), is the primary vector of dengue, Zika, and chikungunya fever, among other arboviral diseases. It is also a popular laboratory model in vector biology due to its ease of rearing and manipulation in the lab. Established laboratory strains have been used worldwide in thousands of studies for decades. Laboratory evolution of reference strains and contamination among strains are potential severe problems that could dramatically change experimental outcomes and thus is a concern in vector biology. We analyzed laboratory and field colonies of Ae. aegypti and an Ae. aegypti-derived cell line (Aag2) using 12 microsatellites and ~20,000 SNPs to determine the extent of divergence among laboratory strains and relationships to their wild relatives. We found that 1) laboratory populations are less genetically variable than their field counterparts; 2) colonies bearing the same name obtained from different laboratories may be highly divergent; 3) present genetic composition of the LVP strain used as the genome reference is incompatible with its presumed origin; 4) we document changes in two wild caught colonies over ~16 generations of colonization; and 5) the Aag2 Ae. aegypti cell line has experienced minimal genetic changes within and across laboratories. These results illustrate the degree of variability within and among strains of Ae. aegypti, with implications for cross-study comparisons, and highlight the need of a common mosquito repository and the implementation of strain validation tools. Author summary: Laboratory colonies provide the opportunity to study live organisms in a controlled environment and serve as phenotypic surrogates of their natural populations. Over time, these strains are prone to change as they face novel environments. We analyzed laboratory and field colonies of the yellow fever mosquito (Aedes aegypti), primary vector of dengue, Zika, and chikungunya fever and a model system in vector biology, and an Ae. aegypti-derived cell line (Aag2) to determine genetic similarity between laboratory strains and their wild relatives. We found lower levels of genetic diversity in laboratory populations compared to wild populations, with colonies of the same name diverging over time or likely contaminated. We also found that the genetic composition of the Liverpool strain, used as the reference genome for this species, is inconsistent with historical records that suggest an African origin and instead points to an outside Africa source. Finally, we did not find major genetic changes in Aag2 cell lines across laboratories. Laboratory evolution of reference strains and strain contamination are severe problems that can change experimental outcomes and complicate cross-study comparison. Our results illustrate the need of a common Aedes aegypti repository and the development of strain validation tools. [ABSTRACT FROM AUTHOR]