Selective Constraint on Noncoding Regions of Hominid Genomes

An important challenge for human evolutionary biology is to understand the genetic basis of human–chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids

Primate phylogeny: molecular evidence for a pongid clade excluding humans and a prosimian clade containing tarsiers

Interpretations of molecular data by the modern evolution theory are often sharply inconsistent with paleontological results. This is to be expected since the theory is only true for microevolution and yet fossil records are mostly about macroevolution. The maximum genetic diversity (MGD) hypothesis is a more coherent and complete account of evolution that has yet to meet a single contradiction. Here, molecular data were analyzed based on the MGD to resolve key questions of primate phylogeny. A new method was developed from a novel result predicted by the MGD: genetic non-equidistance to a simpler taxon only in slow but not in fast evolving sequences given non-equidistance in time. This ‘slow clock’ method showed that humans are genetically more distant to orangutans than African apes are and separated from the pongid clade (containing orangutan and African apes) 17.3 million years ago. Also, tarsiers are genetically closer to lorises than simian primates are, suggesting a tarsier-loris clade to the exclusion of simian primates. The validity and internal coherence of the primate phylogeny here were independently verified. The molecular split time of human and pongid calibrated from the fossil record of gorilla, or the fossil times for the radiation of anthropoids/mammals at the K/T boundary and for the Eutheria-Metatheria split in the Early Cretaceous, were independently confirmed from molecular dating calibrated using the fossil split times of tarsier-loris and two other pairs of mammals (mouse-rat and opossum-kangaroo). This remarkable and unprecedented concordance between molecules and fossils provides the latest confirmation of the inseparable unity of genotype and phenotype and the unmatched value of MGD in a coherent interpretation of life history

Gene Loss and Adaptation to Hominids Underlie the Ancient Origin of HIV-1

SummaryHIV-1 resulted from cross-species transmission of SIVcpz, a simian immunodeficiency virus that naturally infects chimpanzees. SIVcpz, in turn, is a recombinant between two SIV lineages from Old World monkeys. Lentiviral interspecies transmissions are partly driven by the evolution and capacity of viral accessory genes, such as vpx, vpr, and vif, to antagonize host antiviral factors, such as SAMHD1 and the APOBEC3 proteins. We show that vpx, which in other lentiviruses antagonizes SAMHD1, was deleted during the creation of SIVcpz. This genomic deletion resulted in the reconstruction of the overlapping vif gene by “overprinting,” creating a unique vif that overlaps in its 3′ end with the vpr gene and can antagonize hominid APOBEC3s. Moreover, passage of SIVs through chimpanzees facilitated the subsequent adaptation of HIV-1 to humans. Thus, HIV-1 originated through a series of gene loss and adaptation events that generated its chimpanzee precursor and lowered the species barrier to human infection

Probability, Populations, Phylogenetics and Hominin Speciation

A number of recent articles have appeared on the hominin Denisova fossil remains. Many of them focus on attempts to produce DNA sequences from the extracted samples. Often these project mtDNA sequences from the fossil remains of a number of Neandertal fossils and the Denisovans in an attempt to understand the evolution of Mid Pleistocene human ancestors. These papers, introduce a number of problems in the interpretation of speciation in hominins. One concerns the degradation of the ancient DNA and its interpretation as authentic genetic information. Another concerns the idea of “species” versus that of “population” and the use of these ideas in the building of evolutionary diagrams to indicate ancestry and extinction. Since I have dealt with the issue of degradation elsewhere (Caldararo,2016) I will limit this paper to ideas of probability, phylogenetics, species and population. A third issue concerns the theory of haplotypes in the mtDNA. Given the severe constraints on mutations in the mtDNA genome to maintain functionality and the purifying processes to reduce such mutations in the ovaries, putative geographic and historical variations seem contradictory. Local diversity and variations in supposed “macrohaplotypes” are explained as back migrations or back mutations which dilutes the robust nature of the theory. A central issue is what does human variation mean, how much population variation has there been in the past and how does this variation distinguish hominid speciation or simply a process of anagenesis. Some businesses today claim to be able to use DNA analysis to discover past ethnic identities and a new niche in restaurants is producing “DNA” menus. Perhaps some caution is in order

Differential virus restriction patterns of rhesus macaque and human APOBEC3A: Implications for lentivirus evolution

AbstractThe human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is widely expressed in macaque tissues, and is degraded in the presence of the human immunodeficiency virus (HIV-1) and simian–human immunodeficiency virus (SHIV) genomes. Our results indicate that rhA3A is a potent inhibitor of SHIVΔvif and to a lesser extent HIV-1Δvif. Unlike hA3A, rhA3A did not inhibit adeno-associated virus 2 (AAV-2) replication and L1 retrotransposition. These data suggest an evolutionary switch in primate A3A virus specificity and provide the first evidence that a primate A3A can inhibit lentivirus replication

Evolution of the human oral microbiome and resource development for ancient metagenomics

The microbes that live in and on our bodies play major roles in health and disease due to their symbiotic relationship with the host. Understanding how these communities adapt to changes in their environment - either by natural or anthropological forces - is currently a critical area of research for improving holistic healthcare. The aim of this thesis was to demonstrate the potential of large-scale shotgun-sequenced ancient dental calculus to study the wider diversity of the oral microbiome. In Manuscript A, I have shown that ancient dental calculus can be used to improve the understanding of past human oral microbiome diversity, after analysing the largest and oldest ancient dental calculus dataset to date. In this manuscript I also present new tools to help improve authentication of ancient microbiomes. Manuscript B describes the repository AncientMetagenomeDir, a community-level resource that lists all public ancient metagenomic sequencing datasets. The resource will allow researchers to efficiently re-use public data to ensure the robusticity and improve the statistical power of future studies. Manuscript C presents an entirely rewritten user-friendly palaeogenomics pipeline following latest software development and bioinformatics best practices. The pipeline nf-core/eager, has been developed in a way that allows for easy integration with large scale computing infrastructure required for such analyses. Importantly, I have extended this genomics pipeline to have in-parallel metagenomic profiling and screening of ancient DNA characteristics. These manuscripts have contributed new insights into the biology and evolution of oral biofilms, but also introduced new open-source and sustainable tools and resources that will allow further investigation of ancient microbiomes

The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae

<p>Abstract</p> <p>Background</p> <p>The parvulin-type peptidyl prolyl <it>cis/trans </it>isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study.</p> <p>Results</p> <p>Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions.</p> <p>Conclusion</p> <p>Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae.</p

Primate proteomic composition of seminal plasma and prostate-specific transglutaminase activity in relation to sexual selection.

Humans (Homo sapiens), chimpanzees (Pan troglodytes), and gorillas (Gorilla gorilla) have diverse mating systems with varying levels of sperm competition. Several seminal plasma genes have been claimed to evolve under positive selection, while others are altered or lost. This study aims to identify biologically relevant differences among seminal plasma proteomes of primates in relation to mating systems and previous genomic studies. Seminal plasma from three individuals of each species were run in triplicate in shotgun liquid chromatography – tandem mass spectrometry (LC-MS/MS) and confirmed with Western blots. Over 7,000 peptides were identified across all individuals; 168 proteins were identified with high confidence, 70 seminal plasma proteins were identified for human, 64 proteins for chimpanzee, and 34 proteins for gorilla. The gorilla seminal plasma proteome has higher variation among individuals and many proteins involved in semen coagulation and liquefaction have been lost. Chimpanzees have approximately 7-fold higher prostate specific transglutaminase (TGM4) expression than humans. TGM4 was not detected in gorillas, supporting pseudogenization of this gene. The structural semenogelin proteins, SEMG1 and SEMG2, were detected in high abundance in only one of three gorilla individuals, and in all three human and chimpanzee individuals. Chimpanzees have significantly higher expression of SEMG1 (~2.5-fold) compared to human; whereas, they only produce a small amount of SEMG2; ~6.5 –fold less than humans. Chimpanzees have roughly 34-fold higher expression of a serine protease inhibitor, SERPINA3 (Serpin Family A Member 3), than humans. SERPINA3 paralogs, SERPINA1 and SERPINA5, also have increased expression (~2.5 –fold) compared to human, and only SERPINA1 was detected in gorilla. SERPINAs may delay protease dissolution of the copulatory plug in chimpanzees. Recombinant human TGM4 and the reconstructed ancestral TGM4 sequence of our last common ancestor (LCA) with chimpanzees (the human-chimpanzee ancestor) proteins were produced and incubated with casein and monodansylcaverdine to determine enzymatic activity. The human-chimpanzee ancestor TGM4 had higher activity compared to human TGM4. Considering the importance of TGM4 in semen coagulation and copulatory plug formation in chimpanzee, the increased activity of the human-chimpanzee ancestor TGM4 may be indicative of elevated female promiscuity of our LCA, perhaps similar to a chimp-like mating system