There is reason to believe that among the key traits that distinguish humans from the primates that are phylogenetically closest to us are cognitive and social abilities as exemplified by language and diverse aspects of social interaction and cultural expression. It is reasonable to speculate that these characteristic human phenotypes are based on differences from closely related species in neural development, which in turn ought to reflect differences in the nucleotide sequences of the genes that encode proteins or RNA molecules involved in this process. A study (1) published in Cell in October of this year by Christopher A. Walsh of Harvard Medical School, his associates, and collaborators from numerous institutions focuses on so-called human accelerated regions (HARs), portions of the human genome that have diverged more rapidly than other regions from the genomes of the species most closely related to humans. Doan et al. sought to identify mutations in HARs that are associated with abnormal cognition and social behavior of the sort that can be found in autism. (more…)
Aminoacyl tRNA Synthetases: Exemplars of the Fluidity of Protein Structure and Function through Phylogenetic History
Earlier this year I was afforded the opportunity to hear Paul Schimmel, of the Scripps Research Institute, lecture on aminoacyl transfer RNA (tRNA) synthetases (aaRSs), a topic on which he is a leading authority. These enzymes attach particular amino acids to specific tRNA molecules for incorporating those amino acids into growing polypeptide chains by ribosomes. The basic features of these enzymes that contribute to the fundamental function of translating messenger RNAs (mRNAs) are conserved from humans through the most evolutionarily primitive single-celled organisms. Thus these enzymes might be presumed to correspond to prototypical vegetative gene products, i.e., gene products necessary for essential cellular functions that have little to do with more recently evolved functions beyond protein synthesis. So, it was extremely interesting to learn that in organisms that arose later in evolution there are other functions, unrelated to aminoacylation of tRNAs, associated with many of the aaRSs. These functions of aaRSs are summarized by Guo and Schimmel (Nature Chem. Biol., 2013).
Malaria-Specific Antibody Diversification via Interchromosomal Insertion of a Non-Immunoglobulin Gene Sequence
Identifying broadly neutralizing antibodies against infectious agents such as influenza A viruses, HIV, and Plasmodium falciparum that display impressive degrees of antigenic variation is a major focus of investigators developing therapeutics and vaccines for pathogens of importance in public health (Corti and Lanzavecchia, 2013). In a previous post, I discussed one study (Klein et al., 2013) illustrating the sorts of unanticipated types of mutations found for broadly neutralizing antibodies against HIV. Lanzavecchia and colleagues have now identified antibodies reactive with antigens encoded by different isolates of Plasmodium falciparum and expressed on infected erythrocytes (Nature, 2015). They find an unexpected source for the heavy chain variable domain amino acid sequences that confer the broad anti-malarial reactivity against proteins in the RIFIN family. (more…)
Eukaryotic Exploitation of Bacterial Anti-Microbial Genes via Trans-Kingdom Horizontal Gene Transfer
An article published online at the Nature web site on November 24 (Chou et al., 2014) presents a fascinating study of examples in which bacterial genes have found their way to a number of distinct eukaryotic lineages including ticks and mites, gastropod (e.g., snails and slugs) and bivalve mollusks (e.g. clams and oysters), and choanoflagellates (a subset of ptotozoans). Type VI secretion amidase effector (Tae) molecules (encoded by tae genes) can kill rival bacteria by degrading their cells walls when delivered into those competing cells. The eukaryotes cited above all have “domesticated amidase effectors” (dae) genes, all of which are extremely similar to one of the four extant bacterial tae genes. Of the four tae genes found in bacterial species, three have been transferred to one or another eukaryotic genome. (more…)
After posting my last commentary on the ongoing Ebola outbreak in West Africa, I listened to the netcast, This Week in Virology (www.twiv.tv), for September 14, 2014. TWiV sessions, hosted by Vincent Racaniello, a well-known virologist at Columbia University, are generally highly informative, typically offering thoughtful discussions about recently published studies pertaining to viruses or addressing broad areas of virus-related research. (more…)