Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.

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Impact of Vitamin B12on Formation of the Tetrachloroethene Reductive Dehalogenase in Desulfitobacterium hafniense Strain Y51

Applied and Environmental Microbiology ◽

10.1128/aem.02173-12 ◽

2012 ◽

Vol 78 (22) ◽

pp. 8025-8032 ◽

Cited By ~ 27

Author(s):

Anika Reinhold ◽

Martin Westermann ◽

Jana Seifert ◽

Martin von Bergen ◽

Torsten Schubert ◽

...

Keyword(s):

Gene Cluster ◽

De Novo ◽

Anaerobic Bacteria ◽

Vitamin B ◽

Content Type ◽

Reductive Dehalogenase ◽

Gene Level ◽

Desulfitobacterium Hafniense ◽

Pce Dehalogenase ◽

The Impact

ABSTRACTCorrinoids are essential cofactors of reductive dehalogenases in anaerobic bacteria. Microorganisms mediating reductive dechlorination as part of their energy metabolism are either capable ofde novocorrinoid biosynthesis (e.g.,Desulfitobacteriumspp.) or dependent on exogenous vitamin B12(e.g.,Dehalococcoidesspp.). In this study, the impact of exogenous vitamin B12(cyanocobalamin) and of tetrachloroethene (PCE) on the synthesis and the subcellular localization of the reductive PCE dehalogenase was investigated in the Gram-positiveDesulfitobacterium hafniensestrain Y51, a bacterium able to synthesize corrinoidsde novo. PCE-depleted cells grown for several subcultivation steps on fumarate as an alternative electron acceptor lost the tetrachloroethene-reductive dehalogenase (PceA) activity by the transposition of thepcegene cluster. In the absence of vitamin B12, a gradual decrease of the PceA activity and protein amount was observed; after 5 subcultivation steps with 10% inoculum, more than 90% of the enzyme activity and of the PceA protein was lost. In the presence of vitamin B12, a significant delay in the decrease of the PceA activity with an ∼90% loss after 20 subcultivation steps was observed. This corresponded to the decrease in thepceAgene level, indicating that exogenous vitamin B12hampered the transposition of thepcegene cluster. In the absence or presence of exogenous vitamin B12, the intracellular corrinoid level decreased in fumarate-grown cells and the PceA precursor formed catalytically inactive, corrinoid-free multiprotein aggregates. The data indicate that exogenous vitamin B12is not incorporated into the PceA precursor, even though it affects the transposition of thepcegene cluster.

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Human population growth and the demographic transition

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2009.0137 ◽

2009 ◽

Vol 364 (1532) ◽

pp. 2985-2990 ◽

Cited By ~ 200

Author(s):

John Bongaarts

Keyword(s):

Life Expectancy ◽

Demographic Change ◽

Demographic Transition ◽

Human Population ◽

High Fertility ◽

Demographic Transitions ◽

The World ◽

Demographic Processes ◽

Older Populations ◽

Developed World

The world and most regions and countries are experiencing unprecedentedly rapid demographic change. The most obvious example of this change is the huge expansion of human numbers: four billion have been added since 1950. Projections for the next half century expect a highly divergent world, with stagnation or potential decline in parts of the developed world and continued rapid growth in the least developed regions. Other demographic processes are also undergoing extraordinary change: women's fertility has dropped rapidly and life expectancy has risen to new highs. Past trends in fertility and mortality have led to very young populations in high fertility countries in the developing world and to increasingly older populations in the developed world. Contemporary societies are now at very different stages of their demographic transitions. This paper summarizes key trends in population size, fertility and mortality, and age structures during these transitions. The focus is on the century from 1950 to 2050, which covers the period of most rapid global demographic transformation.

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Human Evolution

Notes for a Short Course: Studies in Geology ◽

10.1017/s0271164800000968 ◽

1984 ◽

Vol 8 ◽

pp. 182-198

Author(s):

Catherine Badgley

Keyword(s):

Human Evolution ◽

Evolutionary History ◽

Pan Paniscus ◽

Homo Sapiens ◽

Great Apes ◽

Sister Group ◽

The Family ◽

History Of ◽

Living Species ◽

Single Living

The evolutionary history of humans is well understood in outline, compared to that of many other groups of mammals. But human evolution remains enigmatic in its details, and these are compelling both scientifically and personally because they relate to the biological uniqueness of humans. Humans are placed in the primate family Hominidae, which, in traditional classifications, contains a single living species, Homo sapiens. The closest living relatives of humans are great apes: the chimpanzees Pan paniscus and Pan troglodytes, the gorilla Gorilla gorilla, and the orangutan Pongo pygmaeus. These apes have traditionally been placed in the family Pongidae as the sister group of Hominidae. Living Hominidae and Pongidae, together with Hylobatidae (gibbons) comprise the modern representatives of the primate suborder Hominoidea.

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Body composition inPan paniscuscompared withHomo sapienshas implications for changes during human evolution

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1505071112 ◽

2015 ◽

Vol 112 (24) ◽

pp. 7466-7471 ◽

Cited By ~ 24

Author(s):

Adrienne L. Zihlman ◽

Debra R. Bolter

Keyword(s):

Body Composition ◽

Muscle Mass ◽

Human Evolution ◽

Soft Tissues ◽

Pan Paniscus ◽

Homo Sapiens ◽

The Body ◽

Lower Limbs ◽

Relative Mass ◽

Human Form

The human body has been shaped by natural selection during the past 4–5 million years. Fossils preserve bones and teeth but lack muscle, skin, fat, and organs. To understand the evolution of the human form, information about both soft and hard tissues of our ancestors is needed. Our closest living relatives of the genusPanprovide the best comparative model to those ancestors. Here, we present data on the body composition of 13 bonobos (Pan paniscus) measured during anatomical dissections and compare the data withHomo sapiens. These comparative data suggest that both females and males (i) increased body fat, (ii) decreased relative muscle mass, (iii) redistributed muscle mass to lower limbs, and (iv) decreased relative mass of skin during human evolution. Comparison of soft tissues betweenPanandHomoprovides new insights into the function and evolution of body composition.

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ELFN1-AS1: A Novel Primate Gene with Possible MicroRNA Function Expressed Predominantly in Human Tumors

BioMed Research International ◽

10.1155/2014/398097 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Dmitrii E. Polev ◽

Iuliia K. Karnaukhova ◽

Larisa L. Krukovskaya ◽

Andrei P. Kozlov

Keyword(s):

De Novo ◽

Human Gene ◽

Homo Sapiens ◽

Genomic Analysis ◽

Structure Characteristic ◽

Comparative Genomic ◽

Protein Coding ◽

Regulatory Motifs ◽

Normal Tissues ◽

Microrna Function

Human geneLOC100505644 uncharacterized LOC100505644 [Homo sapiens](Entrez Gene ID 100505644) is abundantly expressed in tumors but weakly expressed in few normal tissues. Till now the function of this gene remains unknown. Here we identified the chromosomal borders of the transcribed region and the major splice form of theLOC100505644-specific transcript. We characterised the major regulatory motifs of the gene and its splice sites. Analysis of the secondary structure of the major transcript variant revealed a hairpin-like structure characteristic for precursor microRNAs. Comparative genomic analysis of the locus showed that it originated in primatesde novo. Taken together, our data indicate that human geneLOC100505644encodes some non-protein coding RNA, likely a microRNA. It was assigned a gene symbolELFN1-AS1(ELFN1 antisense RNA 1 (non-protein coding)). This gene combines features of evolutionary novelty and predominant expression in tumors.

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Elucidation of roles for vitamin B12 in regulation of folate, ubiquinone, and methionine metabolism

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1612360114 ◽

2017 ◽

Vol 114 (7) ◽

pp. E1205-E1214 ◽

Cited By ~ 37

Author(s):

Margaret F. Romine ◽

Dmitry A. Rodionov ◽

Yukari Maezato ◽

Lindsey N. Anderson ◽

Premchendar Nandhikonda ◽

...

Keyword(s):

Vitamin B12 ◽

Microbial Communities ◽

Binding Proteins ◽

De Novo ◽

Transcriptional Regulator ◽

Vitamin B ◽

Methionine Metabolism ◽

Community Metabolism ◽

Light Sensing ◽

Allosteric Effector

Only a small fraction of vitamin B12-requiring organisms are able to synthesize B12 de novo, making it a common commodity in microbial communities. Initially recognized as an enzyme cofactor of a few enzymes, recent studies have revealed additional B12-binding enzymes and regulatory roles for B12. Here we report the development and use of a B12-based chemical probe to identify B12-binding proteins in a nonphototrophic B12-producing bacterium. Two unexpected discoveries resulted from this study. First, we identified a light-sensing B12-binding transcriptional regulator and demonstrated that it controls folate and ubiquinone biosynthesis. Second, our probe captured proteins involved in folate, methionine, and ubiquinone metabolism, suggesting that it may play a role as an allosteric effector of these processes. These metabolic processes produce precursors for synthesis of DNA, RNA, and protein. Thereby, B12 likely modulates growth, and by limiting its availability to auxotrophs, B12-producing organisms may facilitate coordination of community metabolism.

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De novo cobalamin biosynthesis, transport and assimilation and cobalamin-mediated regulation of methionine biosynthesis in Mycobacterium smegmatis

10.1101/2020.11.04.369181 ◽

2020 ◽

Author(s):

Terry Kipkorir ◽

Gabriel T. Mashabela ◽

Timothy J. De Wet ◽

Anastasia Koch ◽

Lubbe Wiesner ◽

...

Keyword(s):

Mycobacterium Smegmatis ◽

De Novo ◽

Time Lapse ◽

Methionine Synthase ◽

Vitamin B ◽

Human Pathogen ◽

Methionine Biosynthesis ◽

Gene And Protein Expression ◽

Cobalamin Biosynthesis

ABSTRACTCobalamin is an essential co-factor in all domains of life, yet its biosynthesis is restricted to some bacteria and archaea. Mycobacterium smegmatis, an environmental saprophyte frequently used as surrogate for the obligate human pathogen, M. tuberculosis, carries approximately 30 genes predicted to be involved in de novo cobalamin biosynthesis. M. smegmatis also encodes multiple cobalamin-dependent enzymes, including MetH, a methionine synthase which catalyses the final reaction in methionine biosynthesis. In addition to metH, M. smegmatis possesses a cobalamin-independent methionine synthase, metE, suggesting that enzyme selection – MetH or MetE – is regulated by cobalamin availability. Consistent with this notion, we previously described a cobalamin-sensing riboswitch controlling metE expression in M. tuberculosis. Here, we apply a targeted mass spectrometry-based approach to confirm de novo cobalamin biosynthesis in M. smegmatis during aerobic growth in vitro. We also demonstrate that M. smegmatis transports and assimilates exogenous cyanocobalamin (CNCbl; a.k.a. vitamin B12) and its precursor, dicyanocobinamide ((CN)2Cbi). Interestingly, the uptake of CNCbl and (CN)2Cbi appears restricted in M. smegmatis and dependent on the conditional essentiality of the cobalamin-dependent methionine synthase. Using gene and protein expression analyses combined with single-cell growth kinetics and live-cell time-lapse microscopy, we show that transcription and translation of metE are strongly attenuated by endogenous cobalamin. These results support the inference that metH essentiality in M. smegmatis results from riboswitch-mediated repression of MetE expression. Moreover, differences observed in cobalamin-dependent metabolism between M. smegmatis and M. tuberculosis provide some insight into the selective pressures which might have shaped mycobacterial metabolism for pathogenicity.IMPORTANCEAccumulating evidence suggests that alterations in cobalamin-dependent metabolism marked the evolution of Mycobacterium tuberculosis from an environmental ancestor to an obligate human pathogen. However, the roles of cobalamin in mycobacterial physiology and pathogenicity remain poorly understood. We used the non-pathogenic saprophyte, M. smegmatis, to investigate the production of cobalamin, transport and assimilation of cobalamin precursors, and the potential role of cobalamin in regulating methionine biosynthesis. We provide biochemical and genetic evidence confirming constitutive de novo cobalamin biosynthesis in M. smegmatis under standard laboratory conditions, in contrast with M. tuberculosis, which appears to lack de novo cobalamin biosynthetic capacity. We also demonstrate that the uptake of cyanocobalamin (vitamin B12) and its precursors is restricted in M. smegmatis, apparently depending on the need to service the co-factor requirements of the cobalamin-dependent methionine synthase. These observations support the utility of M. smegmatis as a model to elucidate key metabolic adaptations enabling mycobacterial pathogenicity.

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Accuracy of de novo assembly of DNA sequences from double-digest libraries varies substantially among software

10.1101/706531 ◽

2019 ◽

Author(s):

Melanie E. F. LaCava ◽

Ellen O. Aikens ◽

Libby C. Megna ◽

Gregg Randolph ◽

Charley Hubbard ◽

...

Keyword(s):

Dna Sequences ◽

De Novo ◽

Homo Sapiens ◽

Simulated Data ◽

Model Organisms ◽

Reduced Representation ◽

Insertion And Deletion ◽

Large Sets ◽

Sequencing Library ◽

Software Programs

AbstractAdvances in DNA sequencing have made it feasible to gather genomic data for non-model organisms and large sets of individuals, often using methods for sequencing subsets of the genome. Several of these methods sequence DNA associated with endonuclease restriction sites (various RAD and GBS methods). For use in taxa without a reference genome, these methods rely on de novo assembly of fragments in the sequencing library. Many of the software options available for this application were originally developed for other assembly types and we do not know their accuracy for reduced representation libraries. To address this important knowledge gap, we simulated data from the Arabidopsis thaliana and Homo sapiens genomes and compared de novo assemblies by six software programs that are commonly used or promising for this purpose (ABySS, CD-HIT, Stacks, Stacks2, Velvet and VSEARCH). We simulated different mutation rates and types of mutations, and then applied the six assemblers to the simulated datasets, varying assembly parameters. We found substantial variation in software performance across simulations and parameter settings. ABySS failed to recover any true genome fragments, and Velvet and VSEARCH performed poorly for most simulations. Stacks and Stacks2 produced accurate assemblies of simulations containing SNPs, but the addition of insertion and deletion mutations decreased their performance. CD-HIT was the only assembler that consistently recovered a high proportion of true genome fragments. Here, we demonstrate the substantial difference in the accuracy of assemblies from different software programs and the importance of comparing assemblies that result from different parameter settings.

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Inhibiting Pyridoxal Kinase of Entamoeba histolytica Is Lethal for This Pathogen

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.660466 ◽

2021 ◽

Vol 11 ◽

Author(s):

Suneeta Devi ◽

Priya Tomar ◽

Khaja Faisal Tarique ◽

Samudrala Gourinath

Keyword(s):

Entamoeba Histolytica ◽

Drug Targets ◽

Cultured Cells ◽

De Novo ◽

Active Form ◽

Protozoan Parasite ◽

Vitamin B ◽

Pyridoxal Kinase ◽

Small Molecule Libraries

Pyridoxal 5’-phosphate (PLP) functions as a cofactor for hundreds of different enzymes that are crucial to the survival of microorganisms. PLP-dependent enzymes have been extensively characterized and proposed as drug targets in Entamoeba histolytica. This pathogen is unable to synthesize vitamin B6via de-novo pathway and relies on the uptake of vitamin B6 vitamers from the host which are then phosphorylated by the enzyme pyridoxal kinase to produce PLP, the active form of vitamin B6. Previous studies from our lab shows that EhPLK is essential for the survival and growth of this protozoan parasite and its active site differs significantly with respect to its human homologue making it a potential drug target. In-silico screening of EhPLK against small molecule libraries were performed and top five ranked molecules were shortlisted on the basis of docking scores. These compounds dock into the PLP binding site of the enzyme such that binding of these compounds hinders the binding of substrate. Of these five compounds, two compounds showed inhibitory activity with IC50 values between 100-250 μM when tested in-vitro. The effect of these compounds proved to be extremely lethal for Entamoeba trophozoites in cultured cells as the growth was hampered by 91.5% and 89.5% when grown in the presence of these compounds over the period of 72 hours.

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Selection for Decreased BRCA2 Functional Activity in Homo sapiens After Divergence from the Chimpanzee-Human Last Common Ancestor

10.1101/2020.11.16.384677 ◽

2020 ◽

Author(s):

Jinlong Huang ◽

Yi Zhong ◽

Alvin P. Makohon-Moore ◽

Travis White ◽

Maria Jasin ◽

...

Keyword(s):

Human Evolution ◽

Functional Activity ◽

Protein Function ◽

Common Ancestor ◽

Homo Sapiens ◽

Last Common Ancestor ◽

Nucleotide Polymorphisms ◽

Cancer Genes ◽

Dna Double Strand Breaks ◽

Bioinformatics Analyses

AbstractHumans have an increased incidence of epithelial neoplasia compared to non-human primates. We performed a comparative analysis of 21 non-human primate genomes and 54 ancient human genomes to identify variations in known cancer genes that may explain this difference. We identified 299 human-specific fixed non-silent single nucleotide polymorphisms. Bioinformatics analyses for functional consequences identified a number of variants predicted to have altered protein function, one of which was located at the most evolutionarily conserved domain of human BRCA2. This variant, in which a polar threonine residue replaces a hydrophobic methionine residue to codon 2662 within the DSS1 binding domain, decreases the interactions of BRCA2 with other proteins, specifically the binding of BRCA2 and RAD51, as well as the repairing ability of cells for DNA double-strand breaks. We conclude that a 20% reduction in BRCA2 DNA repair ability was positively selected for in the course of human evolution.One Sentence SummaryReduction of BRCA2 functional activity has been selected for during human evolution since the chimpanzee-human last common ancestor.

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