Evolution of methyltransferase like (METTL) proteins in Metazoa


The Problem

To understand how epigenetic mechanisms facilitate eukaryotic complexity and evolution, it is important to assess epigenetic regulators and the evolutionary processes that drive their diversification. Methylation is one of the most abundant epigenetic modifications and is widespread across the kingdoms of life. Methyltransferases are enzymes that catalyze the transfer of methyl groups. Members of the methyltransferase-like (METTL) gene family target different types of substrate molecules (i.e., either nucleic acids or protein residues). For instance, some METTL enzymes target and modify RNA molecules, thereby contributing to RNA epigenetics, or epitranscriptomics. Thus, METTL enzymes can influence changes in gene expression and phenotype that can influence an organism's condition. Unfortunately, most METTLs are still poorly characterized, and studies are largely limited to model species.

The Approach

I explored the evolutionary mechanisms driving the diversification and functional differentiation of individual METTL proteins across Metazoa. I found that METTLs are nearly ubiquitous across the animal kingdom. I conducted multiple phylogenetic and evolutionary analyses using METTL sequences from across metazoan taxa. The rate of evolution of various METTL lineages differ by the type of substrate that they modify. The long-term evolution of METTL family members was driven by strong purifying selection, which in combination with adaptive selection episodes, led to the functional specialization of individual METTL lineages.

Related publication

Juliet M. Wong and Jose M. Eirin-Lopez (2021) Evolution of methyltransferase like (METTL) proteins in Metazoa: A complex gene family involved in epitranscriptomic regulation and other epigenetic processes. Molecular Biology and Evolution msab267. https://doi.org/10.1093/molbev/msab267.