New research suggests that a Ser138Asp substitution in prM, a structural protein of Zika virus, contributed to the 2013 outbreak of the virus in French Polynesia. Researchers found that strains of the virus isolated in 2015–2016 caused higher mortality and more severe microcephaly in neonatal mice and had a higher rate of replication in mouse and human neural progenitor cells than did an ancestral strain isolated in 2010. One of the genetic changes present in the more recent Zika strains is a Ser138Asp substitution; the team found that reversal of this mutation also reversed the increased virulence and infectivity of the strain. Analysis of Zika virus evolution revealed that the Ser138Asp mutation first appeared in May 2013, shortly before the outbreak in October 2013, and has been maintained subsequently, suggesting that it contributed to the severe microcephaly observed in the Zika virus epidemic.