Evolutionary genetics and implications of small size and twinning in callitrichine primates

New World monkeys (NWMs) are characterized by an extensive size range, with clawed NWMs (subfamily Callitrichinae, or callitrichines) such as the common marmoset manifesting diminutive size and unique reproductive adaptations. Perhaps the most notable of these adaptations is their propensity toward multiple gestations (i.e., dichorionic twins and trichorionic triplets). Indeed, with the exception of Goeldi's monkey (Callimico), callitrichine singleton pregnancies rarely occur. Multiple gestations seem to have coevolved with a suite of reproductive adaptations, including hematopoetic chimerism of siblings, suppression of reproduction in nondominant females, and cooperative alloparenting. The sequencing of the common marmoset (Callithrix jacchus) genome offers the opportunity to explore the genetic basis of these unusual traits within this primate lineage. In this study, we hypothesized that genetic changes arising during callitrichine evolution resulted in multiple ovulated ova with each cycle, and that these changes triggered adaptations that minimized complications common to multiple gestations in other primates, including humans. Callitrichine-specific nonsynonymous substitutions were identified in GDF9, BMP15, BMP4, and WFIKKN1. WFIKKN1, a multidomain protease inhibitor that binds growth factors and bone morphogenetic proteins, has nonsynonymous changes found exclusively in common marmosets and other tested callitrichine species that twin. In the one callitrichine species that does not produce twins (Callimico), this change has reverted back to the ancestral (nontwinning) primate sequence. Polymorphisms in GDF9 occur among human cohorts with a propensity for dizygotic twins, and polymorphisms in GDF9 and BMP15 are associated with twinning in sheep. We postulate that positive selection affected NWM growth patterns, with callitrichine miniaturization coevolving with a series of reproductive adaptations.