Über die Autorin bzw. den Autor

Mark Lucock, PhD, is a Senior Lecturer in Human Molecular Nutrition at the University of Newcastle School of Environmental and Life Sciences, New South Wales, Australia. Dr. Lucock is internationally recognized as a pioneer in the field of human nutrition, nutrition and genomics, and nutrition and evolution.

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Learn how nutrition has driven―and continues to drive―human evolution

This pioneering text draws from molecular nutrition, nutritional sciences, dietetics, genetics, genomics, and anthropology to examine how chemical nutrients and genetics shape the human species. It presents a vital portrait of the fundamental role that nutrition has played and continues to play in shaping who and what human beings are, where we evolved from, and where we might be headed as a species.

The author's innovative molecular biological approach moves the field of nutrition well beyond its traditional dietetic and anthropological origins to the front lines of genomic research. Following a presentation of molecular biology concepts that are essential for the study of human nutrition, the author explores such key topics as:

• Bioinformatics and the -omics revolution

• Recent human evolution

• Molecular mechanisms of gene-nutrient interactions

• Role of nutrients and genomics in disease

• Evolution of micronutrient metabolism, protein structure, and human disease

• Nutrients and the human life cycle

• Mismatch of contemporary dietary patterns and our genetic makeup

• Laboratory tools for nutrigenomics and human evolutionary studies

Figures and illustrations provided throughout the text help readers grasp and visualize complex concepts and processes with ease. For readers interested in pursuing particular topics in greater depth, an extensive list of current references is provided.

This text is ideal for undergraduate and graduate students in human nutrition, dietetics, metabolism, molecular biology, and many other allied health sciences. Nowhere else can readers find such an integrated blend of medical, nutritional, and biochemical disciplines to aid in understanding the role of nutrients in human evolution.

Aus dem Klappentext

Learn how nutrition has driven—and continues to drive—human evolution

This pioneering text draws from molecular nutrition, nutritional sciences, dietetics, genetics, genomics, and anthropology to examine how chemical nutrients and genetics shape the human species. It presents a vital portrait of the fundamental role that nutrition has played and continues to play in shaping who and what human beings are, where we evolved from, and where we might be headed as a species.

The author's innovative molecular biological approach moves the field of nutrition well beyond its traditional dietetic and anthropological origins to the front lines of genomic research. Following a presentation of molecular biology concepts that are essential for the study of human nutrition, the author explores such key topics as:

• Bioinformatics and the -omics revolution

• Recent human evolution

• Molecular mechanisms of gene-nutrient interactions

• Role of nutrients and genomics in disease

• Evolution of micronutrient metabolism, protein structure, and human disease

• Nutrients and the human life cycle

• Mismatch of contemporary dietary patterns and our genetic makeup

• Laboratory tools for nutrigenomics and human evolutionary studies

Figures and illustrations provided throughout the text help readers grasp and visualize complex concepts and processes with ease. For readers interested in pursuing particular topics in greater depth, an extensive list of current references is provided.

This text is ideal for undergraduate and graduate students in human nutrition, dietetics, metabolism, molecular biology, and many other allied health sciences. Nowhere else can readers find such an integrated blend of medical, nutritional, and biochemical disciplines to aid in understanding the role of nutrients in human evolution.

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Molecular Nutrition and Genomics

John Wiley & Sons

Chapter One

1.1 KEY CONCEPTS IN MOLECULAR BIOLOGY FOR THE STUDY OF HUMAN NUTRITION

Until very recently, the study of human nutrition and molecular biology were considered to be mutually exclusive domains within the biological sciences. This is simply no longer the case. Today, the leading edge of our endeavor to explain the very nature of mankind, and our ascent to planetary dominance blends both nutrition and molecular biology into the fields of nutritional genetics and nutrigenomics. These new disciplines exploit our knowledge of the human genome and its variability to explain how nutrients, their dependent proteins, and encoding genes conspire to forge and maintain our species. These interactions not only help explain the etiology of many diseases, but also they provide a framework for gaining a better understanding of the likely evolution of our species. Human evolution was forged out of our ancestors obligate need to forage for chemical nutrients that varied in their abundance according to habitat and season. This forced early humans to find and compete for limited resources; humans that foraged optimally and competed most successfully for those resources were fitter and more able to reproduce and, hence, could pass on their genetic material to their progeny. In other words, they were selected for. This process of evolution is characterized by a change in gene frequency over time, but what are genes, and how do they lead to the expression of traits, the summation of which produces the state of "being human?" To understand this process, we need to examine the building blocks of our genetic code.

1.1.1 Molecular Structure of DNA

Polymeric DNA is composed of four different nucleotides. Each nucleotide consists of a 2'-deoxyribose sugar, purine or pyrimidine base, and phosphate moiety. Purine bases are either adenine or guanine, whereas pyrimidine bases are either thymine or cytosine. When a base is linked to the 1' carbon of the deoxyribose sugar, it is referred to as a nucleoside. When, in addition, phosphate moieties are attached to the sugar, the structure is referred to as a nucleotide.

Nucleotide triphosphates (Figure 1.1) of adenine (A), guanine (G), cytosine (C), and thymine (T) are polymerized to form DNA via phosphodiester bond formation between the 5' phosphate of one nucleotide and the 3' hydroxyl group of the next nucleotide. The sequence of bases is what encodes the genetic blueprint for life. It can be read in the 5' [right arrow] 3' or the 3' [right arrow] 5' direction.

The primary sequence of DNA permits a three-dimensional structure to form, which is represented by a double helix. The sugar-phosphate linkage forms the molecular backbone of this structure. The bases face inward and stabilize the double helix via hydrogen bonds between adjacent T and A bases, and again between adjacent G and C bases. This base pairing is specific, and purine always interacts with pyrimidine, a phenomenon referred to as "complementary base pairing." The double helix is right-handed with a turn every 10 bases. Examination of the structure reveals a major molecular groove, which facilitates protein interactions.

Complimentary base pairing ensures that the sequence of one DNA strand predicts the base sequence of the other. This simple fact is what permits the fidelity of the genetic blueprint to be preserved during replication of DNA as part of cell division, and during the expression of genes.

Expression of DNA, which is the conversion of the base sequence blueprint into an amino acid sequence within a functional protein, requires as a first step, the transcription of the DNA sequence into an RNA transcript. RNA is the same as DNA except RNA contains uracil, whereas DNA contains thymine (Figure 1.2). Additionally, in RNA, ribose replaces DNA's 2-deoxyribose. The RNA transcript is referred to as messenger RNA (mRNA). mRNA is then translated into a protein on the ribosome-transfer RNAs (tRNA) are small molecules that coordinate individual amino acids to form proteins that have been specified by the mRNA sequence.

This phenomenon of gene expression in which the biological data encoded by a gene is made available in terms of a functional protein is referred to as "the central dogma." That is, information is passed from DNA to RNA to protein.

Humans contain around 23,000 genes on 23 chromosomes. These genes are separated by intergenic (noncoding) DNA. Although a gene is the fundamental unit of information in that a single gene codes for a single polypeptide, higher organisms such as man also have multigene families. In their simplest form, a gene family contains more than one copy of a gene where its expression product is required in large amounts. Complex multigene families also exist. These yield similar, but distinct, proteins with related function, for example, the globin polypeptides.

To orchestrate gene regulation according to cellular need, gene promoter regions exist upstream from the coding region of a gene. Promoter sites bind the enzyme for synthesizing the RNA transcript (RNA polymerase II) and any associated transcription factors that are required to initiate mRNA synthesis. Promoter regions usually contain a TATA box around 25 base pairs upstream from the site at which transcription commences. Transcription factors bind DNA around the TATA box and orchestrate the binding of RNA polymerase II. RNA polymerases I and III are associated with transcription of ribosomal RNAs and genes encoding tRNAs, respectively.

Transcription factors can be considered as modular molecules that contain DNA binding, dimerization, and transactivation modalities. These regulatory factors exhibit characteristic structural motifs. The DNA binding modality contains three potential motifs: zinc fingers, basic domains, and helix-turn-helix motifs. Dimerization modalities contain two motifs: leucine zippers and helix-loop-helix structural motifs. The formation of homo-and heterodimers leads to transcription factor variation and, hence, a diversity of function. Transcription factors can act to both initiate and repress transcription.

Genes do not contain a continuous code; rather they are split into coding regions known as exons and noncoding regions known as introns. Introns are removed from the RNA transcript by a process referred to as splicing. This process occurs before protein synthesis. Some genes have accumulated nonsense errors in their base sequence and no longer function. These archaic genes are referred to as pseudogenes.

1.1.2 Molecular Encryption

The base sequence of DNA encodes the amino acid sequence of a polypeptide via the intermediate polymer-RNA. Amino acids are encrypted by 64 triplets; each triplet represents a sequence of three DNA bases and is known as a codon. Within a gene, each set of codons that builds up to form a genetic unit of information is referred to as a reading frame. The reading frame is determined by "initiation" and "stop" codons. In between these initiation and stop codons, one has what is referred to as an "open reading frame."

As the four nucleic acid bases can combine to form 64 permutations of codon (Table 1.1), but only 20 amino acids exist in proteins, all amino acids save tryptophan and methionine are encrypted by more than one codon. This fact is why the genetic code is often referred to as having built-in degeneracy...