This chapter introduces genetics and looks at the history of genes. It considers properties of genes, such as inheritance, allelism, linkage, and mutation. Gregor Mendel correctly identified that genes are inherited as cellular elements. He noted also that diploid organisms have two copies of each gene. The chapter shows how various gene components were identified since Mendel's discovery, including how Thomas Hunt Morgan found that genes are affixed on chromosomes at varying positions. The chapter describes how most genomes are transcribed and numerous genes encode RNA as their final product. The chapter considers why scientists are unable to name every gene that is discovered, and explains how genetic analysis uses the properties of genes as an approach to solve or dissect a complex biological problem.
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The basis for genetic analysis
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The Biochemical Basis of Heredity
This chapter addresses the biochemical basis of heredity. Nucleotides, which polymerize to form long chains, are the building blocks of DNA and RNA. A DNA molecule consists of two chains of nucleotides coiled around each other to form a double helix, while an RNA molecule consists of a single chain. The DNA double helix is formed by complementary base pairing between nucleotides on opposite strands. During DNA replication, the two strands separate and each becomes a template for the synthesis of a new strand. The sequence of nucleotides encodes the genetic information. The chapter then looks at the types of DNA sequence as well as transposable elements.
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The biogenesis and nucleocytoplasmic traffic of non-coding RNAs
This chapter explores non-coding RNAs (ncRNAs) that are processed during their biogenesis. It covers the processing and maturation of ribosomal RNA (rRNA), small nuclear RNA (snRNA), transfer RNA (tRNA), mitochondrial transcripts, and telomerase. It also gives an overview of the important aspects of RNA processing, including the RNA processing machinery that involves the action of other RNA molecules. The chapter reviews the main features of the biogenesis of ribosomal RNA, which is a process that is facilitated by a family of small RNA molecules known as the small nucleolar RNAs (snoRNAs). It describes the organization of rRNA processing in an important multifunctional nuclear organelle, the nucleolus.
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Cancer Genomics
This chapter discusses cancer genomics, which is one of the fastest-moving areas of medical research and is having a direct impact on people's lives. Cancer is a disease in which cells divide in excess, generating a lump, known as the primary tumour. A key feature of cancer is that the cells in the lump spread, invading the neighbouring normal tissues and blood and lymphatic vessels, allowing them to colonize distant organs, forming distant secondary tumours. Both primary and secondary tumours may cause symptoms as they penetrate and grow into normal tissues. The genome changes in cancers include single nucleotide changes, amplifications or deletions of regions of chromosomes, and chromosome rearrangements that may join genes together. The chapter considers how understanding the genome of cancer cells can help us prevent and treat cancer, and improve the survival and quality of life of patients.
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Catalytic RNAs
This chapter looks at how RNA molecules catalyse chemical reactions, a domain which was previously thought to be reserved only for proteins. It clarifies that RNA has a more limited set of functional groups for building catalysts, which are confined to just four different nucleotides: A, C, G, and U. It also highlights the ability of RNA molecules to form structures which also enables the assembly of RNA active sites. The chapter outlines the important function of metal ions in ribozymes, which includes helping RNA structures form and balance the strong negative charge in ribozyme active sites that result from high densities of RNA strands. It also mentions that the purine and pyrimidine bases of RNA have NH groups that can potentially act as hydrogen donors or acceptors in acid-base catalysis.
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The Cellular Basis for Mendelian Genetics
The chapter examines the process of meiosis, which discusses on a cellular and molecular level the inheritance patterns that Gregor Mendel observed. It shows how the genome of the cell is halved during meiosis, with each resulting cell containing one of the two members of a homologous pair of chromosomes. It also recounts the biologists that recognized Mendel’s patterns of inheritance and that the segregation of chromosomes during meiosis were two sides of the same biological coin. The chapter describes the behaviour of chromosomes during meiosis, which is the cellular basis of Mendel’s Law of Segregation that states that alleles for each gene separate from each other during the production of gametes. It clarifies how the Mendelian inheritance can be integrated with the observed movement of chromosomes in meiosis and the changes in DNA during the process of gamete production.
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The Central Dogma of Molecular Biology
This chapter explains that the Central Dogma of molecular biology is that DNA provides the template to make RNA, which provides the template to make a polypeptide that contributes to phenotypes. It illustrates the structure of DNA and the Central Dogma, highlighting features of the DNA molecule that have an impact on its function. It points out modifications to the traditional view of the Central Dogma and introduces the basic structure of a gene. The chapter describes information content that flows from DNA to RNA to polypeptide, which is inherent in the structures of the molecules and encodes the amino acid sequence of the polypeptide. It also shows that, according to genome analysis, a surprising number of RNA molecules do not serve as templates for making polypeptides but are functional themselves.
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Chromosome Mutations
This chapter discusses chromosome mutations, during which one or a few chromosomes may be lost or gained (aneuploidy). Common aneuploid conditions include monosomy and trisomy; nullisomy and tetrasomy also occur. The addition of whole sets of chromosomes produces polyploid cells. Meanwhile, segments of individual chromosomes can be deleted, duplicated, become incorporated in other chromosomes, or inverted. Chromosome mutations often arise through errors during meiosis. In turn, chromosomal mutations frequently disrupt the process of meiosis, resulting in unbalanced gametes. The chapter then looks at how changes in chromosomal structure and number often occur in tumour cells. It also considers how chromosome mutations play important roles in evolution.
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Chromosomes and Cellular Reproduction
This chapter discusses chromosomes and cellular reproduction. Living organisms are classified as prokaryotes or eukaryotes. Eukaryotic cells have a more complex structure, and each eukaryotic species has a characteristic number of chromosomes. Each eukaryotic chromosome contains a single long linear deoxyribonucleic acid (DNA) molecule which is tightly packed. The chapter looks at sex chromosomes and sex determination, before considering the cell cycle. The cell cycle describes the different stages that a eukaryotic cell passes through from one cell division to the next. The chapter then explains mitosis and meiosis. Mitosis results in the production of two genetically identical cells and meiosis leads to the formation of four genetically variable cells with half the chromosome number.
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Co-transcriptional pre-mRNA processing
This chapter discusses the pre-mRNA processing events that occur co-transcriptionally. It covers the synthesis of the 7-methyl guanosine 5? cap, pre-mRNA splicing, and the formation of the 3? end of an mRNA by cleavage and polyadenylation. It also considers the connections that exist between chromatin structure and pre-mRNA processing, including the special case of metazoan histone mRNA 3? end formation. The chapter reviews the essential elements of the process of transcription, structure, and function of the RNA polymerases. It explores the process of transcription that is required to appreciate the links between transcription and pre-mRNA processing events, as well asthe connection between transcription and post-transcriptional processes that is illustrated by the properties of the C-terminal domain (CTD) of RNA polymerase II.
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Comparative Genomics
This chapter analyses the three major divisions of living things (archaea, bacteria, and eukaryotes) based on the sequences of 16S rRNA genes. It notes the prevalence of historical gene transfer among prokaryotes. Historical gene transfer is not consistent with the hierarchical Linnaean classification scheme. The chapter discusses the general distribution of genome sizes and gene numbers while determining the characteristics of different types of genome organization in viruses, prokaryotes, and eukaryotes. The chapter notes the impact of gene duplication on genome evolution and considers the mechanism of genome change at the levels of individual bases, genes, chromosome segments, and whole genomes. It differentiates homologue, orthologue, and paralogue as well. The chapter also expounds on the human genome and the idea of a model organism in the study of human diseases.
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Connecting phenotypes with DNA sequences
This chapter shows how we can connect mutant phenotypes to the corresponding DNA sequence after the mutations had been identified and classified. The process is colloquially known as cloning the gene. The chapter looks at complementation tests and sequence analysis which are often conducted to confirm the causative gene of the phenotype. The chapter presents the processes that have helped identify the causative genes for some rare genetic human conditions. The chapter also looks at the process of a typical gene-cloning strategy which includes mapping a mutant phenotype or looking at genes transcribed in a pattern. It explains how the DNA sequence corresponding to a mutant or variant phenotype can now be identified directly, by sequencing the genomes or the exons of affected individuals.
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Control of Gene Expression
This chapter studies the control of gene expression. The expression of most genes in prokaryotes and eukaryotes is regulated, i.e. genes are switched on and off according to a cell’s needs. This prevents cells’ resources being wasted. A low percentage of a cell’s genes, those that encode basic cellular functions, are expressed continually. In prokaryotes, changes in gene expression tend to be in response to environmental signals, while in eukaryotes, differential gene expression tends to be related to developmental stage. Gene expression can be regulated at various points between genotype and phenotype. In prokaryotes, most control mechanisms regulate the transcription of genes, while eukaryotes employ various translational as well as transcriptional control mechanisms.
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Descent with Modification: Continuity and Variation in the Genome
This chapter talks about DNA replication, and it repairs and ties this topic to Charles Darwin’s concept of ‘descent with modification’, a fundamental principle of natural selection and evolution. It presents several challenges to DNA replication that arise from its length and anti-parallel structure, including the processes that have evolved to address these challenges. It also introduces the many types of mutation that occur, and how the occurrence of such mutations and the effects of selection can be revealed by comparing the genomes of different organisms. The chapter shows how to reconstruct evolutionary history and develop phylogenetic trees based on DNA sequence changes. It highlights the principle of descent with modification, which demonstrates the balance between two competing evolutionary pressures.
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Epistasis and genetic pathways
This chapter explains epistasis, whereby the phenotype of one gene masks the phenotype of a different gene, and describes how it can be exploited to construct the logical pathway of the gene interactions that underlie a biological process. It notes that every biological process is the outcome of genes or gene products working together in pathways and networks, which may be linear or branched, and may involve many genes or few genes. The chapter discusses how gene interactions in negative, positive, and parallel pathways are inferred by using double mutants.
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Eukaryotic Gene Mapping
This chapter evaluates eukaryotic gene mapping, which is often a two-part process involving genetic and physical mapping. Genetic mapping uses traditional Mendelian analysis of carefully constructed genetic crosses to produce maps showing the relative positions of genes and other features on a chromosome; this analysis identifies approximate gene positions. Meanwhile, physical mapping employs molecular techniques, e.g. DNA sequencing, to directly examine the DNA of chromosomes to determine the precise position of genes. The chapter then looks at gene mapping using trihybrid crosses, before considering how human genes are mapped by examining pedigrees for the co-segregation of traits. It also studies how logarithm of odds (LOD) scores are calculated, using data from human pedigrees, to assess the likelihood of linkage of two genes.
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Evolution and Genomic Change
This chapter focuses on the coordination of changes in genotype and phenotype during evolution. It considers evolution to be an exploration that leads to discovery and change. It expounds on the principles of biological classification and the grammar of biological nomenclature, citing the biological taxonomy used for identifying different life forms. It differentiates between similarity and homology as well. It shows the measurements of similarities between gene or protein sequences amongst different species. The chapter explains the construction and calculation of phylogenetic trees, which are diagrams showing ancestordescendant relationships. The chapter includes a description of the general idea of pattern recognition and introduces tools used in an effort to recognize similarities among sequences. It lists types of pattern matching, which is a basic tool of bioinformatics, such as dot plot and the BLOSUM62 matrix.
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Evolution, Genomes, and Genetics
This chapter introduces a recent study of the genomes of Charles Darwin’s finches, which identified genes that contribute to the differences in beak shape among the species. It links one of the most important and familiar examples of natural selection among Darwin’s finches with the underlying genetic and genomic basis for the differences observed among the birds. It also uses Darwin’s finches to discuss DNA, molecules, phenotypes, species, and evolution in a community of organisms. The chapter explores the current availability of genomic information from many species of bacteria, plants, and animals. It highlights how evolution has shaped DNA sequences, genes, and genomes throughout biology.
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Exchange and Evolution
This chapter introduces the process of horizontal gene transfer that is originally found among bacteria, but now known to occur in other types of organisms. It describes horizontal gene transfer, which is a process wherein organisms acquire DNA from other individuals over the course of their lifetime. It also highlights the importance of horizontal gene acquisition in shaping the content and structure of genomes that occurs within and across all kingdoms of life. The chapter looks at instances of extensive horizontal gene transfer that challenge the traditional view of evolutionary lineages as ‘branching trees’, although limited horizontal gene transfer has profound evolutionary consequences. It talks about cells that reproduce asexually, which can have new combinations of alleles and polymorphisms or even entirely new genes, as DNA has been acquired from another cell in the population or from the environment.
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From Genotype to Phenotype I: RNA and Transcription
This chapter describes ribonucleic acid (RNA) and transcription. RNA is an intermediary in the flow of information from genotype to phenotype. In living organisms, genetic information passes from deoxyribonucleic acid (DNA) to RNA. Different types of RNA perform different roles in the information transfer from genotype to phenotype. Transcription is the process of RNA synthesis from a DNA template, and it is catalysed by RNA polymerases. Transcription involves three distinct phases: initiation, elongation, and termination. In eukaryotes, there is extensive post-transcriptional processing of the primary RNA transcript. The chapter also looks at prokaryotic transcription and the details of messenger RNA (mRNA) capping and splicing.
