Autism, the Evolution of Homo sapiens sapiens, and the Definition of “Human”

Autism, the Evolution of Homo sapiens sapiens, and the Definition of “Human”

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…)

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…)

Illumination of the Multiple Sources of Selection Affecting Protein Sequences

Biomedical scientists and biologists routinely consider how selection shapes the structure and function of proteins of interest.  Less commonly, I suspect, do we consider how selection for attributes other than protein structure and function can favor or disfavor nucleotide sequences that encode particular amino acid sequences.   A new study (Stergachis et al., 2013) published in the December 13 issue of Science presents strong evidence for one particular source of selection (unrelated to protein function) influencing coding regions, known as exons, of genes.  This form of selection arises from the  fact, as revealed by the authors, that many transcription factors (TF), proteins that bind to specific nucleotide  sequences and regulate the frequency and pace of gene transcription (i.e., gene expression), bind in exonic regions of genes. (more…)