Every eukaryotic chromosome has a centromere, the locus responsible for poleward movement at mitosis and meiosis. Although conventional loci are specified by their DNA sequences, current evidence favors a chromatin-based inheritance mechanism for centromeres. The chromosome segregation machinery is highly conserved across all eukaryotes, but the DNA and protein components specific to centromeric chromatin are evolving rapidly. Incompatibilities between rapidly evolving centromeric components may be responsible for both the organization of centromeric regions and the reproductive isolation of emerging species.
Primate genomes encode a variety of innate immune strategies to defend themselves against retroviruses. One of these, TRIM5␣, can restrict diverse retroviruses in a species-specific manner. Thus, whereas rhesus TRIM5␣ can strongly restrict HIV-1, human TRIM5␣ only has weak HIV-1 restriction. The biology of TRIM5␣ restriction suggests that it is locked in an antagonistic conflict with the proteins encoding the viral capsid. Such antagonistic interactions frequently result in rapid amino acid replacements at the proteinprotein interface, as each genetic entity vies for evolutionary dominance. By analyzing its evolutionary history, we find strong evidence for ancient positive selection in the primate TRIM5␣ gene. This selection is strikingly variable with some of the strongest selection occurring in the human lineage. This history suggests that TRIM5␣ evolution has been driven by antagonistic interactions with a wide variety of viruses and endogenous retroviruses that predate the origin of primate lentiviruses. A 13-aa ''patch'' in the SPRY protein domain bears a dense concentration of positively selected residues, potentially implicating it as an antiviral interface. By using functional studies of chimeric TRIM5␣ genes, we show that this patch is generally essential for retroviral restriction and is responsible for most of the species-specific antiretroviral restriction activity. Our study highlights the power of evolutionary analyses, in which positive selection identifies not only the age of genetic conflict but also the interaction interface where this conflict plays out.capsid ͉ human endogenous retroviruses ͉ HIV type 1 ͉ SPRY
Histones are best known as the architectural proteins that package the DNA of eukaryotic organisms, forming octameric nucleosome cores that the double helix wraps tightly around. Although histones have traditionally been viewed as slowly evolving scaffold proteins that lack diversification beyond their abundant tail modifications, recent studies have revealed that variant histones have evolved for diverse functions. H2A and H3 variants have diversified to assume roles in epigenetic silencing, gene expression and centromere function. Such diversification of histone variants and 'deviants' contradicts the perception of histones as monotonous members of multigene families that indiscriminately package and compact the genome. How these diverse functions have evolved from ancestral forms can be addressed by applying phylogenetic tools to increasingly abundant sequence data.
Mammalian genes and genomes have been shaped by ancient and ongoing challenges from viruses. These genetic imprints can be identified via evolutionary analyses to reveal fundamental details about when (how old), where (which protein domains), and how (what are the functional consequences of adaptive changes) host-virus arms races alter the proteins involved. Just as extreme amino acid conservation can serve to identify key immutable residues in enzymes, positively selected residues point to molecular recognition interfaces between host and viral proteins that have adapted and counter-adapted in a long series of classical Red Queen conflicts. Common rules for the strategies employed by both hosts and viruses have emerged from case studies of innate immunity genes in primates. We are now poised to use these rules to transition from a retrospective view of host-virus arms races to specific predictions about which host genes face pathogen antagonism and how those genetic conflicts transform host and virus evolution.
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