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Knapp, L. A.

Publications and source records attributed to Knapp, L. A..

2 recordsLinked to original sources

Positively selected variants in functionally important regions of TLR7 in Alouatta guariba clamitans with yellow fever virus exposure in Northern Argentina

1In 2007-2009, a ma jor yellow fever virus (YFV) outbreak in Northern Argentina decimated the local howler monkey (Alouatta) population. We explored the relationship between Toll-like receptor (TLR) 7 and TLR8 gene variation and YFV susceptibility using samples from Alouatta individuals alive before the YFV outbreak, individuals that died during the outbreak, and individuals that survived the outbreak and are alive today. We measured genetic divergence between Alouatta YFV exposure groups and evaluated Alouatta-specific substitutions for functional consequences. We did not find different allele frequencies in the post-YFV exposure Alouatta group compared to the pre-exposure group. However, we identified three nonsynonymous variants in TLR7 in A. guariba clamitans. Two of these substitutions are under positive selection in functionally important regions of the gene. These unique coding differences in A. guariba clamitans may affect YFV resistance, but more work is necessary to fully explore this hypothesis.

evolutionary biology

Comparing the selective landscape of TLR7 and TLR8 across primates reveals unique sites under positive selection in Alouatta

Among primates, susceptibility to yellow fever (YFV), a single-stranded (ss) RNA virus, ranges from complete resistance to high susceptibility. Howler monkeys (genus Alouatta) are the most susceptible to YFV. In order to identify Alouatta-specific genetic factors that may be responsible for their susceptibility, we collected skin samples from howler monkey museum specimens of the species A. caraya and A. guariba clamitans. We compared the rate of nonsynonymous to synonymous (dN/dS) changes of Toll-like receptor (TLR) 7 and TLR8, the two genes responsible for detecting all ssRNA viruses, across the Primate order. Overall, we found that the TLR7 gene is under stronger purifying selection in howler monkeys compared to other New World and Old World primates, but TLR8 is under the same selective pressure. When we evaluated dN/dS at each codon, we found six codons under positive selection in Alouatta TLR8 and two codons under positive selection in TLR7. The changes in TLR7 are unique to A. guariba clamitans and are found in functionally important regions likely to affect detection of ssRNA viruses by TLR7/TLR8, as well as downstream signaling. These amino acid differences in A. guariba clamitans may play a role in YFV susceptibility. These results have implications for identifying genetic factors affecting YFV susceptibility in primates.

evolutionary biology