1. 'Evo-Devo' to Complement the Prevalence of 'Devo-Evo'.
The field of the evolution of development (or evo-devo) has expanded dramatically in the past decade with the proliferation of straightforward techniques for studying gene expression divergence among multiple species. Nevertheless, many of the most exciting cues about how divergence in gene regulatory patterns and networks may have shaped major evolutionary adaptations have been restricted to case studies of individual or small groups of genes. Furthermore, it remains difficult to determine whether observed regulatory differences between species are themselves adaptive or the byproduct of other evolutionary processes. Large-scale interspecific comparative gene regulation studies in the context of development are lacking and yet are crucial to a more complete synthesis of evolution and development (Artieri and Singh 2010a).
In order to remedy this deficiency, I am interested in identifying regulatory changes in closely related species using genome-scale approaches. Taking advantage of our ability to create hybrids of closely-related species, we can unmask the mechanistic basis of regulatory divergence by uncovering differences in parental allelic expression resulting from cis- and trans-regulatory changes (Wittkopp et al. 2004). Furthermore, we can use these data in order to identify regulatory changes that are adaptive, and thus begin to dissect the evolutionary pressures that have been responsible for the observed divergence (see Fraser 2011 for an overview of detecting adaptation).
During my doctoral dissertation, I focused on comparing patterns of coding sequence and expression divergence of Drosophila genes in the context of multiple developmental stages and tissues and found clear signals that developmental timing of expression influences evolutionary patterns (see Artieri et al. 2009; Artieri and Singh 2010b). My more recent work has focused on studying divergence of gene expression patterns during the very earliest stages of Drosophila development - specifically during the maternal-to-zygotic transition - or when maternally deposited RNAs cede responsability for maintaining the embryonic transcriptome to RNAs derived from the zygotic genome (see Tadros and Lipschitz 2009 for review). This developmental transition provides an unprecedented opportunity to examine regulatory divergence in a complex organism as expression from the zygotic genome begins. Furthermore, it obviates complications related to the interpretation of transcriptional profiles derived from pools of multiple tissues and cell types.
2. Regulatory Evolution of Translation
The studies of gene regulatory evolution discussed above have focused almost entirely on transcriptional regulation and are contingent on the assumption that gene expression is an appropriate proxy for protein abundance - the latter of which is what ultimately carries out the function of most expressed loci. Because of the technical challenges associated with measuring the abundance of proteins on a genome wide scale, very little is known about how translational regulation differs among species. However, a novel method named 'ribo-profiling', which takes advantage of next-generation sequencing technologies has allowed us to observe cellular translational profiles at base-level resolution (Ingolia et al. 2012).
A major focus of my current research has been to adapt ribo-profiling for use in simultaneously detecting regulatory divergence at both the transcriptional and translational levels. Using techniques pioneered in our lab, I am currently in the process of exploring adaptive regulatory divergence at multiple levels and exploring their relative levels of prevalence, whether adaptation occurs independently in transcription and translation, and if changes are typically reinforcing or compensatory, among many others.