Structural and Genetic Determinants of Convergence in the Drosophila tRNA Structure-Function Map.

The evolution of tRNA multigene families remains poorly understood, exhibiting unusual phenomena such as functional conversions of tRNA genes through anticodon shift substitutions. We improved FlyBase tRNA gene annotations from twelve Drosophila species, incorporating previously identified ortholog sets to compare substitution rates across tRNA bodies at single-site and base-pair resolution. All rapidly evolving sites fell within the same metal ion-binding pocket that lies at the interface of the two major stacked helical domains. We applied our tRNA Structure-Function Mapper (tSFM) method independently to each Drosophila species and one outgroup species Musca domestica and found that, although predicted tRNA structure-function maps are generally highly conserved in flies, one tRNA Class-Informative Feature (CIF) within the rapidly evolving ion-binding pocket-Cytosine 17 (C17), ancestrally informative for lysylation identity-independently gained asparaginylation identity and substituted in parallel across tRNAAsn paralogs at least once, possibly multiple times, during evolution of the genus. In D. melanogaster, most tRNALys and tRNAAsn genes are co-arrayed in one large heterologous gene cluster, suggesting that heterologous gene conversion as well as structural similarities of tRNA-binding interfaces in the closely related asparaginyl-tRNA synthetase (AsnRS) and lysyl-tRNA synthetase (LysRS) proteins may have played a role in these changes. A previously identified Asn-to-Lys anticodon shift substitution in D. ananassae may have arisen to compensate for the convergent and parallel gains of C17 in tRNAAsn paralogs in that lineage. Our results underscore the functional and evolutionary relevance of our tRNA structure-function map predictions and illuminate multiple genomic and structural factors contributing to rapid, parallel and compensatory evolution of tRNA multigene families.

Is preterm birth a human-specific syndrome?

Human preterm birth (PTB), a multifactorial syndrome affecting offspring born before 37 completed weeks of gestation, is the leading cause of newborn death worldwide. Remarkably, the degree to which early parturition contributes to mortality in other placental mammals remains unclear. To gain insights on whether PTB is a human-specific syndrome, we examined within- and between-species variation in gestation length across placental mammals and the impact of early parturition on offspring fitness. Within species, gestation length is normally distributed, and all species appear to occasionally give birth before the 'optimal' time. Furthermore, human gestation length, like that of many mammalian species, scales proportionally to body mass, suggesting that this trait, like many others, is constrained by body size. Premature humans suffer from numerous cognitive impairments, but little is known of cognitive impairments in other placental mammals. Human gestation differs in the timing of the 'brain growth spurt', where unlike many mammals, including closely related primates, the trajectory of human brain growth directly overlaps with the parturition time window. Thus, although all mammals experience early parturition, the fitness costs imposed by the cognitive impairments may be unique to our species. Describing PTB broadly in mammals opens avenues for comparative studies on the physiological and genetic regulators of birth timing as well as the development of new mammalian models of the disease.