The term junk DNA has been used to describe DNA that does not code for proteins or polypeptides. Recent research has made this term obsolete, and Nessa Carey elaborates on a wide spectrum of examples of ways in which DNA contributes to cell function in addition to coding for proteins. As in her earlier book, The Epigenetics Revolution (reviewed by ABT in 2013), Carey uses analogies and diagrams to relate complicated information. Although she unavoidably uses some jargon, she provides the necessary background for the nonbiologist.
Carey, a visiting professor at Imperial College, London, invokes many cases of human diseases to introduce the additional DNA functions as well as to explain how scientists came to understand them. Readers familiar with the PBS Nova episode “Ghost in Your Genes” will be familiar with the example of Angelman and Prader-Willi syndromes, where the disease is differentially expressed depending on whether a chromosome error was inherited from the child's mother or father. A process called “imprinting” identifies a chromosome as maternally or paternally derived. Here, Carey discusses the imprinting control element (ICE), a region of DNA that is methylated or not during gamete formation. If there is no methylation, as happens during sperm formation, a long noncoding RNA molecule is produced, which then represses a cluster of nearby genes. As a result, only the maternally inherited cluster of genes is expressed in the child. In describing research into the two syndromes, Carey writes about uniparental disomy (where a child appears to have the normal complement of 46 chromosomes, but with a homologous pair originating from one parent instead of both parents) and about noncoding RNA that determines the expression of different noncoding RNA molecules that, in turn, regulate additional RNA molecules.
Centromeres are usually mentioned in any textbook discussion of mitosis, but I had never before encountered a description of what they are: a long series of repeated 171-base-pair sequences to which the protein CENP-A is attached. CENP-A not only is the cornerstone of the protein complex to which spindle fibers attach, but also replaces a pair of histone proteins in the nucleosomes along that region of the chromosome. The location of the CENP-A–histone complexes is passed on during cell reproduction. The underlying DNA sequence neither codes for protein nor is well conserved. Rather, that DNA acts as a placeholder.
In eukaryotic cells, the initial RNA formed from a gene during transcription is edited; sections known as introns are removed and the remaining exons are spliced together by structures called “spliceosomes.” Those exons will then be used by ribosomes as directions for assembling chains of amino acids according to the genetic code. Biology textbooks include a table of the genetic code, showing how the 64 codons match to 20 amino acids. In discussing splice signals in the DNA that identify to spliceosomes which portions of the transcribed RNA are introns and exons, Carey describes the mutation associated with one type of progeria, where children develop symptoms of old age. That mutation substitutes one codon for glycine with another for that same amino acid in an exon. Familiarity with the genetic code might lead one to think that this mutation would be neutral, having no effect on the protein and no effect on phenotype. However, the protein produced is too short because the spliceosome interacts differently with the sequence, recognizing an extra splicing site because of the codon difference.
Carey also discusses telomeres, X-inactivation, small nucleolar RNA, microRNA, small interfering RNA, stem cells, ENCODE, enhancers, HOX genes, and more. Biology teachers looking to expand their knowledge in these areas will find a wealth of clearly described information that goes beyond high school or first-year college textbooks. An extensive notes section is helpful for those seeking primary source materials. An appendix of human diseases discussed can make this a useful classroom resource for teachers who assign genetic-disease projects to students.
As a biology teacher who enjoys sharing with students some details that go beyond the textbook or that challenge dogma, I enthusiastically read multiple chapters at each sitting, making note of what I cannot wait to add to class discussions. “Junk DNA” may be a misnomer, but Junk DNA is an excellent way of finding out why.