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The trajectory of human aging varies widely from one individual to the next due to complex interactions between the genome and the environment that influence the aging process. Such differences in age-specific mortality and disease risk among same-aged individuals reflect variation in the pace of biological aging. Certain mechanisms involved in the progression of biological aging originate in the epigenome, where chemical modifications to the genome are able to alter gene expression without modifying the underlying DNA sequence. The epigenome serves as an interface for environmental signals, which are able to "get under the skin" to influence health and aging. A number of the molecular mechanisms involved in the aging process have been identified, although few aging phenotypes have been definitively traced to their underlying molecular causes thus far. In this review, we discuss variation in human biological aging and the epigenome's role in promoting heterogeneity in human longevity and healthspan. [ABSTRACT FROM AUTHOR]

Over 40 species of nonhuman primates host simian immunodeficiency viruses (SIVs). In natural hosts, infection is generally assumed to be nonpathogenic due to a long coevolutionary history between host and virus, although pathogenicity is difficult to study in wild nonhuman primates. We used whole-blood RNA-seq and SIV prevalence from 29 wild Ugandan red colobus (Piliocolobus tephrosceles) to assess the effects of SIV infection on host gene expression in wild, naturally SIV-infected primates. We found no evidence for chronic immune activation in infected individuals, suggesting that SIV is not immunocompromising in this species, in contrast to human immunodeficiency virus in humans. Notably, an immunosuppressive gene, CD101 , was upregulated in infected individuals. This gene has not been previously described in the context of nonpathogenic SIV infection. This expands the known variation associated with SIV infection in natural hosts and may suggest a novel mechanism for tolerance of SIV infection in the Ugandan red colobus. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Telomere length (TL) is a biomarker of aging and age‐related decline. Although venous blood is considered the “gold standard” for TL measurement, its collection is often not feasible or desired in nonclinical settings. Saliva and dried blood spots (DBS) have been used as alternatives when venipuncture cannot be performed. However, it is not known whether these sample types yield TL measurements comparable to those obtained from venous blood. We sought to determine whether different samples from the same individual yield comparable TL measurements. Methods: We extracted DNA from matched buffy coat, saliva (Oragene and Oasis), and DBS (venous and capillary) samples from 40 women aged 18‐77 years. We used the monochrome multiplex qPCR (MMQPCR) assay to measure TL in all sample types for each participant and applied quality control measures to retain only high‐quality samples for analysis. We then compared TL from buffy coat and saliva to examine how these measurements differ and to test if TL is correlated across sample types. Results: TL differed significantly across buffy coat, Oragene saliva, and Oasis saliva samples. TL from buffy coat and Oragene saliva was moderately correlated (ρ = 0.48, P = .002) and the most similar in size. Oasis saliva TL was not correlated with buffy coat or Oragene saliva TL, and was the shortest. DBS DNA yields were inadequate for TL measurement using the MMQPCR assay. Conclusions: Using a matched dataset we demonstrate that sample type significantly influences the TL measurement obtained using the MMQPCR assay. [ABSTRACT FROM AUTHOR]

Few studies have combined genetic association analyses with functional characterization of infection-associated SNPs in natural populations of nonhuman primates. Here, we investigate the relationship between host genetic variation, parasitism and natural selection in a population of red colobus ( Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. We collected parasitological, cellular and genomic data to test the following hypotheses: (i) MHC- DQA1 regulatory genetic variation is associated with control of whipworm ( Trichuris) infection in a natural population of red colobus; (ii) infection-associated SNPs are functional in driving differential gene expression in vitro; and (iii) balancing selection has shaped patterns of variation in the MHC- DQA1 promoter. We identified two SNPs in the MHC- DQA1 promoter, both in transcription factor binding sites, and both of which are associated with decreased control of Trichuris infection. We characterized the function of both SNPs by testing differences in gene expression between the two alleles of each SNP in two mammalian cell lines. Alleles of one of the SNPs drove differential gene expression in both cell lines, while the other SNP drove differences in expression in one of the cell lines. Additionally, we found evidence of balancing selection acting on the MHC- DQA1 promoter, including extensive trans-species polymorphisms between red colobus and other primates, and an excess of intermediate-frequency alleles relative to genome-wide, coding and noncoding RADseq data. Our data suggest that balancing selection provides adaptive regulatory flexibility that outweighs the consequences of increased parasite infection intensity in heterozygotes. [ABSTRACT FROM AUTHOR]

Objectives The obesity epidemic in Mexico is increasing and represents a considerable public health challenge. The population aged 50 years and older is also increasing and is not exempt from the obesity rise. We aimed to determine the current prevalence of Body Mass Index (BMI) categories in a sample of Mexicans aged 50 years and older and to test the associations of BMI with physical activity categories and related factors. Methods Data from 2,032 individuals aged 50 years and older who participated in SAGE Wave 1 (2009-2010) were analyzed. Representativeness of the sample was obtained by using weighted data. Descriptive statistics, chi square tests, simple regression analysis, and multiple regression analysis were performed in relation to BMI, self-reported physical activity categories, and several variables, including demographic characteristics and selected risk factors for non-communicable diseases. Results Among older adults, 0.6% was found to be underweight, 21.4% normal weight, 49.4% overweight, and 28.7% obese. It was also found that practicing vigorous intensity physical activity (−1.32) and being 80 years or older (−2.73) were significantly associated ( P < 0.05) with a lower mean BMI (28.3). In contrast, being in the lowest income quintile (1.35), and living in urban areas (0.86) were significantly associated with a higher mean BMI. Conclusions The study results contribute to the current understanding of obesity etiology in Mexico, and moreover confirm that overweight and obesity are current public health problems that must be addressed in specific subgroups of older adults. Am. J. Hum. Biol. 27:326-333, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives Human brain development follows a unique pattern characterized by a prolonged period of postnatal growth and reorganization, and a postnatal peak in glucose utilization. The molecular processes underlying these developmental changes are poorly characterized. The objectives of this study were to determine developmental trajectories of gene expression and to examine the evolutionary history of genes differentially expressed as a function of age. Methods We used microarrays to determine age-related patterns of mRNA expression in human cerebral cortical samples ranging from infancy to adulthood. In contrast to previous developmental gene expression studies of human neocortex that relied on postmortem tissue, we measured mRNA expression from the nondiseased margins of surgically resected tissue. We used regression models designed to identify transcripts that followed significant linear or curvilinear functions of age and used population genetics techniques to examine the evolution of these genes. Results We identified 40 transcripts with significant age-related trajectories in expression. Ten genes have documented roles in nervous system development and energy metabolism, others are novel candidates in brain development. Sixteen transcripts showed similar patterns of expression, characterized by decreasing expression during childhood. Comparative genomic analyses revealed that the regulatory regions of three genes have evidence of adaptive evolution in recent human evolution. Conclusions These findings provide evidence that a subset of genes expressed in the human cerebral cortex broadly mirror developmental patterns of cortical glucose consumption. Whether there is a causal relationship between gene expression and glucose utilization remains to be determined. Am. J. Hum. Biol. 25:418-430, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: A primary objective of molecular phylogenetics is to use molecular data to elucidate the evolutionary history of living organisms. Dr. Morris Goodman founded the journal Molecular Phylogenetics and Evolution as a forum where scientists could further our knowledge about the tree of life, and he recognized that the inference of species trees is a first and fundamental step to addressing many important evolutionary questions. In particular, Dr. Goodman was interested in obtaining a complete picture of the primate species tree in order to provide an evolutionary context for the study of human adaptations. A number of recent studies use multi-locus datasets to infer well-resolved and well-supported primate phylogenetic trees using consensus approaches (e.g., supermatrices). It is therefore tempting to assume that we have a complete picture of the primate tree, especially above the species level. However, recent theoretical and empirical work in the field of molecular phylogenetics demonstrates that consensus methods might provide a false sense of support at certain nodes. In this brief review we discuss the current state of primate molecular phylogenetics and highlight the importance of exploring the use of coalescent-based analyses that have the potential to better utilize information contained in multi-locus data. [Copyright &y& Elsevier]

The chorioallantoic placenta connects mother and fetus in eutherian pregnancies. In order to understand the evolution of the placenta and provide further understanding of placenta biology, we sequenced the transcriptome of a term placenta of an African elephant (Loxodonta africana) and compared these data with RNA sequence and microarray data from other eutherian placentas including human, mouse, and cow. We characterized the composition of 55,910 expressed sequence tag (i.e., cDNA) contigs using our custom annotation pipeline. A Markov algorithm was used to cluster orthologs of human, mouse, cow, and elephant placenta transcripts. We found 2,963 genes are commonly expressed in the placentas of these eutherian mammals. Gene ontology categories previously suggested to be important for placenta function (e.g., estrogen receptor signaling pathway, cell motion and migration, and adherens junctions) were significantly enriched in these eutherian placenta–expressed genes. Genes duplicated in different lineages and also specifically expressed in the placenta contribute to the great diversity observed in mammalian placenta anatomy. We identified 1,365 human lineage–specific, 1,235 mouse lineage–specific, 436 cow lineage–specific, and 904 elephant-specific placenta-expressed (PE) genes. The most enriched clusters of human-specific PE genes are signal/glycoprotein and immunoglobulin, and humans possess a deeply invasive human hemochorial placenta that comes into direct contact with maternal immune cells. Inference of phylogenetically conserved and derived transcripts demonstrates the power of comparative transcriptomics to trace placenta evolution and variation across mammals and identified candidate genes that may be important in the normal function of the human placenta, and their dysfunction may be related to human pregnancy complications. [ABSTRACT FROM AUTHOR]

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR=0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development. [ABSTRACT FROM AUTHOR]

Adrenarche is a developmental event involving differentiation of the adrenal gland and production of adrenal androgens, and has been hypothesized to play a role in the extension of the preadolescent phase of human ontogeny. It remains unclear whether any nonhuman primate species shows a similar suite of endocrine, biochemical, and morphological changes as are encompassed by human adrenarche. Here, we report serum concentrations of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) measured in 698 cross-sectional and mixed longitudinal serum samples from catarrhine primates ranging from 0.6 to 47 years of age. DHEAS in Pan is most similar to that of humans in both age-related pattern and absolute levels, and a transient early increase appears to be present in Gorilla. DHEA levels are highest in Cercocebus, Cercopithecus, and Macaca. We also tested for evidence of adaptive evolution in six genes that code for proteins involved in DHEA/S synthesis. Our genetic analyses demonstrate the protein-coding regions of these genes are highly conserved among sampled primates. We describe a tandem gene duplication event probably mediated by a retrotransposon that resulted in two 3-β-hydroxysteroid dehydrogenase/Delta 5-Delta 4 genes ( HSD3B1 and HSD3B2) with tissue specific functions in catarrhines. In humans, HSD3B2 is expressed primarily in the adrenals, ovary, and testis, while HSD3B1 is expressed in the placenta. Taken together, our findings suggest that while adrenarche has been suggested to be unique to hominoids, the evolutionary roots for this developmental stage are more ancient. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: To obtain a more complete understanding of the evolutionary history of the leaf-eating monkeys we have examined the mitochondrial genome sequence of two African and six Asian colobines. Although taxonomists have proposed grouping the “odd-nosed” colobines (proboscis monkey, douc langur, and the snub-nosed monkey) together, phylogenetic support for such a clade has not been tested using molecular data. Phylogenetic analyses using parsimony, maximum likelihood, and Bayesian methods support a monophyletic clade of odd-nosed colobines consisting of Nasalis, Pygathrix, and Rhinopithecus, with tentative support for Nasalis occupying a basal position within this clade. The African and Asian colobine lineages are inferred to have diverged by 10.8 million years ago (mya or Ma). Within the Asian colobines the odd-nosed clade began to diversify by 6.7Ma. These results augment our understanding of colobine evolution, particularly the nature and timing of the colobine expansion into Asia. This phylogenetic information will aid those developing conservation strategies for these highly endangered, diverse, and unique primates. [Copyright &y& Elsevier]

Abstract: Accurate divergence date estimates improve scenarios of primate evolutionary history and aid in interpretation of the natural history of disease-causing agents. While molecule-based estimates of divergence dates of taxa within the superfamily Hominoidea (apes and humans) are common in the literature, few such estimates are available for the Cercopithecoidea (Old World monkeys), the sister taxon of the hominoids in the primate infraorder Catarrhini. To help fill this gap, we have sequenced the entire mitochondrial DNA (mtDNA) genomes from a representative of three cercopithecoid tribes, Cercopithecini (Chlorocebus aethiops), Colobini (Colobus guereza), and Presbytini (Trachypithecus obscurus), and analyzed these new data together with other catarrhine mtDNA genomes available in public databases. Molecular divergence date estimates are dependent on calibration points gleaned from the paleontological record. We defined criteria for the selection of good calibration points and identified three points meeting these criteria: Homo-Pan, 6.0Ma; Pongo-hominines, 14.0Ma; hominoid/cercopithecoid, 23.0Ma. Because a uniform molecular clock does not fit the catarrhine mtDNA data, we estimated divergence dates using a penalized likelihood and a Bayesian method, both of which take into account the effects of rate differences on lineages, phylogenetic tree structure, and multiple calibration points. The penalized likelihood method applied to the coding regions of the mtDNA genome yielded the following divergence date estimates, with approximate 95% confidence intervals: cercopithecine-colobine, 16.2 (14.4-17.9) Ma; colobin-presbytin, 10.9 (9.6-12.3) Ma; cercopithecin-papionin, 11.6 (10.3-12.9) Ma; and Macaca-Papio, 9.8 (8.6-10.9) Ma. Within the hominoids, the following dates were inferred: hylobatid-hominid, 16.8 (15.0-18.5) Ma; Gorilla-Homo + Pan, 8.1 (7.1-9.0) Ma; Pongo pygmaeus pygmaeus-P. p. abelii, 4.1 (3.5-4.7) Ma; and Pan troglodytes-P. paniscus, 2.4 (2.0-2.7) Ma. These dates were similar to those found using penalized likelihood on other subsets of the data, but slightly younger than several of the Bayesian estimates. [Copyright &y& Elsevier]

Abstract: The phylogenetic position of tarsiers within the primates has been a controversial subject for over a century. Despite numerous morphological and molecular studies, there has been weak support for grouping tarsiers with either strepsirrhine primates in a prosimian clade or with anthropoids in a haplorrhine clade. Here, we take advantage of the recently released whole genome assembly of the Philippine tarsier, Tarsius syrichta, in order to infer the phylogenetic relationship of Tarsius within the order Primates. We also present estimates of divergence times within the primates. Using a 1.26 million base pair multiple sequence alignment derived from 1078 orthologous genes, we provide overwhelming statistical support for the presence of a haplorrhine clade. We also present divergence date estimates using local relaxed molecular clock methods. The estimated time of the most recent common ancestor of extant Primates ranged from 64.9 Ma to 72.6 Ma, and haplorrhines were estimated to have a most recent common ancestor between 58.9 Ma and 68.6 Ma. Examination of rates of nucleotide substitution in the three major extant primate clades show that anthropoids have a slower substitution rate than either strepsirrhines or tarsiers. Our results provide the framework on which primate morphological, reproductive, and genomic features can be reconstructed in the broader context of mammalian phylogeny. [Copyright &y& Elsevier]

Humans are unique among terrestrial mammals in our manner of walking and running, reflecting 7 to 8 Ma of musculoskeletal evolution since diverging with the genus Pan. One component of this is a shift in our skeletal muscle biology towards a predominance of myosin heavy chain (MyHC) I isoforms (i.e. slow fibers) across our pelvis and lower limbs, which distinguishes us from chimpanzees. Here, new MyHC data from 35 pelvis and hind limb muscles of a Western gorilla (Gorilla gorilla) are presented. These data are combined with a similar chimpanzee dataset to assess the MyHC I content of humans in comparison to African apes (chimpanzees and gorillas) and other terrestrial mammals. The responsiveness of human skeletal muscle to behavioral interventions is also compared to the human-African ape differential. Humans are distinct from African apes and among a small group of terrestrial mammals whose pelvis and lower limb muscle is slow fiber dominant, on average. Behavioral interventions, including immobilization, bed rest, spaceflight and exercise, can induce modest decreases and increases in human MyHC I content (i.e. -9.3% to 2.3%, n = 2033 subjects), but these shifts are much smaller than the mean human-African ape differential (i.e. 31%). Taken together, these results indicate muscle fiber content is likely an evolvable trait under selection in the hominin lineage. As such, we highlight potential targets of selection in the genome (e.g. regions that regulate MyHC content) that may play an important role in hominin skeletal muscle evolution. [Display omitted] • Gorilla muscle MyHC content is similar to chimpanzees and distinct from humans. • Human slow fiber content is distinct from African apes and most mammals. • Behavioral interventions (e.g. exercise) induce modest shifts in slow fiber content. • MyHC I content is an evolvable trait under selection within the hominin lineage. • MyHC genes are conserved in mammals so selection likely operates on enhancers. [ABSTRACT FROM AUTHOR]

Anthropoid primates arose during the Eocene approximately 55 million years ago (mya), and extant anthropoids share a most recent common ancestor ∼40 mya. Paleontology has been very successful at describing the morphological phenotypes of extinct anthropoids. Less well understood is the molecular biology of these extinct species as well as the phenotypic consequences of evolutionary variation in their genomes. Here we resurrect the most recent common ancestral anthropoid estrogen receptor β gene ( ESR2 ) and demonstrate that the function of this ancestral estrogen receptor has been maintained during human descent but was altered during early New World monkey (NWM) evolution by becoming a more potent transcriptional activator. We tested hypotheses of adaptive evolution in the protein coding sequences of ESR2 , and determined that ESR2 evolved via episodic positive selection on the NWM stem lineage. We separately co-transfected ESR2 constructs for human, NWM, and the anthropoid ancestor along with reporter gene vectors and performed hormone binding dose response experiments that measure transactivation activity. We found the transactivation potentials of the ancestral and human sequences to be significantly lower (p < 0.0001 in each comparison) than that of the NWM when treated with estradiol, the most prevalent estrogen. We conclude the difference in fold activation is due to positive selection in the NWM ERβ ligand binding domain. Our study validates inferential methods for detecting adaptive evolution that predict functional consequences of nucleotide substitutions and points a way toward examining the functional consequences of positive Darwinian selection. [ABSTRACT FROM AUTHOR]

Highlights: [•] We present one of the largest phylogenies of primates using complete mitochondrial genomes. [•] We included 62 primate species (representing all families) and 25 mammal species. [•] We recovered all the major clades within primates. [•] A cross-validation procedure was used to identify a set of fossil calibrations. [•] Crown primates diversified in the late Cretaceous supporting a short-fuse model. [Copyright &y& Elsevier]

Baboons (Mammalia: Primates, Papio) are found primarily on the continent of Africa, but the range of hamadryas baboons (Papio hamadryas) extends to the Arabian Peninsula, and the origin of Arabian populations is unclear. To estimate the timing of the divergence between Arabian and African hamadryas populations we analyzed mitochondrial DNA (mtDNA) sequences from individuals of Arabian and African origin, and from representatives of the other major baboon taxa. The oldest hamadryas mitochondrial lineages in the Arabian Peninsula form an ancient trichotomy with the two major African lineages. This suggests that Arabia was colonized by hamadryas very soon after the appearance of the distinctive hamadryas phenotype, both events perhaps coinciding with a mid-Pleistocene stage of dry climate and low sea-level. The most closely related Arabian and African mtDNA haplotypes coalesce at approximately 35 ka, suggesting that no gene flow between African and Arabian baboons has occurred since the end of the last ice age, when a land bridge at the southern sill of the Red Sea was submerged. The mitochondrial paraphyly of Ethiopian hamadryas and anubis (P. anubis) baboons suggests an extensive and complex history of sex-specific introgression. [Copyright &y& Elsevier]

Phenotypic aging is ubiquitous across mammalian species, suggesting shared underlying mechanisms of aging. Aging is linked to molecular changes to DNA methylation and gene expression, and environmental factors, such as severe external challenges or adversities, can moderate these age-related changes. Yet, it remains unclear whether environmental adversities affect gene regulation via the same molecular pathways as chronological, or 'primary', aging. Investigating molecular aging in naturalistic animal populations can fill this gap by providing insight into shared molecular mechanisms of aging and the effects of a greater diversity of environmental adversities - particularly those that can be challenging to study in humans or laboratory organisms. Here, we characterised molecular aging - specifically, CpG methylation - in a sample of free-ranging rhesus macaques living off the coast of Puerto Rico (n samples = 571, n individuals = 499), which endured a major hurricane during our study. Age was associated with methylation at 78,661 sites (31% of all sites tested). Age-associated hypermethylation occurred more frequently in areas of active gene regulation, while hypomethylation was enriched in regions that show less activity in immune cells, suggesting these regions may become de-repressed in older individuals. Age-associated hypomethylation also co-occurred with increased chromatin accessibility while hypermethylation showed the opposite trend, hinting at a coordinated, multi-level loss of epigenetic stability during aging. We detected 32,048 CpG sites significantly associated with exposure to a hurricane, and these sites overlapped age-associated sites, most strongly in regulatory regions and most weakly in quiescent regions. Together, our results suggest that environmental adversity may contribute to aging-related molecular phenotypes in regions of active gene transcription, but that primary aging has specific signatures in non-regulatory regions., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Research in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from short-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research owing to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with the model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population. This article is part of the theme issue 'Evolution of the primate ageing process'.

In Charles Darwin's tree model for life's evolution, natural selection adaptively modifies newly arisen species as they branch apart from their common ancestor. In accord with this Darwinian concept, the phylogenomic approach to elucidating adaptive evolution in genes and genomes in the ancestry of modern humans requires a well supported and well sampled phylogeny that accurately places humans and other primates and mammals with respect to one another. For more than a century, first from the comparative immunological work of Nuttall on blood sera and now from comparative genomic studies, molecular findings have demonstrated the close kinship of humans to chimpanzees. The close genetic correspondence of chimpanzees to humans and the relative shortness of our evolutionary separation suggest that most distinctive features of the modern human phenotype had already evolved during our ancestry with chimpanzees. Thus, a phylogenomic assessment of being human should examine earlier stages of human ancestry as well as later stages. In addition, with the availability of a number of mammalian genomes, similarities in phenotype between distantly related taxa should be explored for evidence of convergent or parallel adaptive evolution. As an example, recent phylogenomic evidence has shown that adaptive evolution of aerobic energy metabolism genes may have helped shape such distinctive modern human features as long life spans and enlarged brains in the ancestries of both humans and elephants.