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JSM Biotechnology and Biomedical Engineering

DNA is the Basic Molecule of Inheritance

Review Article | Open Access

  • 1. Independent Researcher, Republic of Croatia
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Corresponding Authors
Siniša Franji?, Independent Researcher, Republic of Croatia
Abstract

Deoxyribonucleic acid (DNA) is a nucleic acid in the form of a double helix. DNA contains genetic instructions for the specific biological development of cellular life forms and most viruses, is a long polymer nucleotide, and encodes the amino acid sequence in proteins using a genetic code, i.e. a triple nucleotide code. It is a polymer of nucleotides made up of pentose de-oxyribose, a phosphate group and a nitrogen base which in DNA can be adenine, guanine, cytosine and thymine. In eukaryotic organisms such as plants, animals, fungi, and protests, most of the DNA is located in the cell nucleus. In simpler organisms called prokaryotes, DNA is not separated from the cytoplasm by a nuclear envelope. Mitochondria and chloroplasts, which are organelles of eukaryotic cells, also contain DNA.

Citation

Franjic S (2021) DNA is the Basic Molecule of Inheritance. JSM Biotechnol Bioeng 7(1): 1089.

Keywords

• DNA
• Human biology
• Cells
• Genetics

INTRODUCTION

DNA is sometimes called the blueprint of life and has characteristics that are appropriate to its role [1]. Many, if not all, of these characteristics are important in Forensic Genetics, which is simply genetics in a legal context. These characteristics include its simplicity and yet complexity, both of which are incorporated within the polymeric chemical structure of the backbone molecule and the varied sequence of side chain bases (the so-called letters of its information content), arranged in a double helix. The molecule is made from a relatively small number of building blocks yet contains a vast amount and range of information that can define the nature of the biological cell, and ultimately the multicellular organism, within which the DNA is located. The double helix structure is relatively stable in time yet is adaptable enough to “open up” to allow a living cell to use the contained information to go about its life functions (transcription) or to make copies of it (replication). DNA is stable so as to enable transfer of the genetic information from generation to generation after replication (with cell division and mating where relevant), yet it can also change to varying extents. Some of the changes are important to only an individual organism and may be deleterious (e.g. mutation giving rise to a cancer), or are the basis for individual variation (e.g. mutation giving rise to a new variant, and the haploid segregation of chromosomes in gametes with the return of diploid pairing at fertilization to produce a new individual). Some changes affect a subpopulation (e.g. lineages) and even eventually an entire population (e.g. natural selection of mutations and new diploid combinations leading to evolutionary change).

Structure

DNA contains the plans that are responsible for the construction of our cells, tissues, organs, and body [2]. DNA houses the information required to produce proteins. Proteins play a number of roles within cells as structural elements (keratin, actin, myosin, tubulin), hormones, antibodies, or enzymes. Less than 5% of our DNA contains the genes that code for the production of proteins. Enzymes are catalysts, chemicals that speed up the rate of a reaction but are not used up in the process. These proteins are necessary for the development and maintenance of cells that are then used to construct tissues. Tissues are groups of cells that function as a unit to form sheets or tubes (building elements). Tissues of different types can become physically and functionally related such that they give rise to organs, such as kidneys and livers. Thus, one can trace the pathway of life from the macromolecule known as DNA to the formation of cells, tissues, organs, and ultimately, to complete organisms.

To provide some perspective about the size of the DNA genome and where it is stored in the cell, imagine that you are able to travel within the cell. Cells are composed of nucleic acids [DNA and ribonucleic acid (RNA)], proteins, lipids, sugars, and a variety of other important molecules. Cells contain a large number of discrete membrane-bound structures, each with a unique and vital function. On this brief journey as you enter the outer cell membrane, you will encounter within the cytoplasm a large spherical nucleus, hundreds (and in some cases, thousands) of mitochondria, ribosomes, lysosomes, a Golgi body, interior membranes (endoplasmic reticulum) that provide channels within the cytoplasm and vacuoles, vesicles, and other structures related to cellular “feeding and drinking.” The intracellular structures of human cells (animal and plant cells are eukaryotic) differ from those of bacterial cells (prokaryotic) that are much more simply organized. In virtually every human cell there is a double membrane-enclosed and somewhat spherical structure called the nucleus. It floats in a liquid medium called the cytoplasm that has characteristics of both a solution and a gel. Most of the cell’s DNA is located in the nucleus and is known as genomic DNA. DNA within the nucleus is invisible to the naked eye as well as to the light microscope. It consists of 46 units. If the 46 molecules were linked end to end the resulting molecule would be 2 meters long, approximately 6 ft. However, it is so thin (20 Ångstrom units) that one requires a transmission electron microscope to magnify its image to visualize it.

Human biology

You only need to glance around a group of people to witness the variability of human biology [3]. On any city sidewalk you can see the complete spectrum of heights, hair colors, body types, and other physical characteristics of the human race. Like your physical characteristics, your DNA sequence is unique; even your closest relative has a different DNA sequence than you do. In the case of identical twins, DNA testing can find differences in the twins ’DNA genome sequences, even though identical twins were thought to have identical DNA genomes. The genomes of identical twins show some regions of variability in DNA sequences that are far less variable than the DNA genomes of different unrelated individuals. The DNA sequence is especially variable at certain locations in the human genome, and it is these variable regions of the DNA genomes that are used to distinguish the DNA from one person and another person, and to determine whether or not they are identical twins.

The results of DNA testing often have consequences that profoundly affect people’s lives. Some results reveal the identity of biological parents, while other forms of DNA testing are used to convict people of crimes that carry serious consequences including the death sentence. DNA testing has been subjected to a great deal of scrutiny by the scientific and legal communities and is studied considerably more than any of the other commonly used forensic investigation techniques. DNA testing and the laboratories that conduct DNA testing have improved greatly in the past decade, and the system has emerged stronger because of the scrutiny. Modern DNA testing methods are highly reliable, and the databases of DNA sequences that are used for criminal and anthropological investigations are already impressive in size and still growing. Large DNA databases are important in order to avoid population biases that affect DNA testing results. DNA testing can be performed on any life form, including plants, animals, bacteria, and viruses, making it a versatile tool capable of answering a diverse array of perplexing questions.

Human body

The human body is a universe of working parts and functional interactions [4]. We observe the physical manifestations of these interactions all the time, as we walk, talk, breathe, think, or eat. These gross or macroscopic functions of the human body, however, are driven by extremely complex interactions, occurring at the cellular and subcellular level. Our bodies are made up of trillions of cells. Each cell has a prescribed function relative to its position in the body that is essential to healthy human life. The cells themselves are extremely complex and advanced pieces of biological machinery. A cell is comprised of a cytosol, which is bound by a permeable membrane, and contains a host of miniature organs (organelles) including the nucleus. The nucleus contains DNA -the material that prescribes the cell’s principal functional characteristics. It may be useful to think of the cell as being like a factory. Membranes enclose the structure and separate different organelles, which can be thought of as departments with specialized functions. The nucleus is the central administration, containing in its DNA a library of information that determines cellular structure and processes. From it instructions are issued for proper regulation of the business of the cell. The mitochondria are the power generators. The cytosol can be thought of as the general work area, where protein machinery (enzymes) carries out the formation of new molecules from imported raw materials. There are special molecular channels in the membranes between compartments and between the cell and its external surroundings. Like factories, cells tend to specialize in function. For example, many of the cells in higher organisms are largely devoted to the production and export of one or a few molecular products.

Despite the diverse functions of the different types of cells that constitute the human body, each nucleated cell contains an identical copy of a common DNA molecule from which genetic information is read in a linear fashion. Since the amount of information needed to specify the structure and function of a multicellular organism such as a human is immense, the DNA molecule is extremely long. In fact, if the DNA from a single human cell were stretched end to end it would extend approximately 2 m.

Genetics

Genetic research has far- reaching implications not just for how we think about child- rearing and schools but how we think about our own adult lives [5]. Genetics is the major systematic influence in our lives, increasingly so as we get older. Therefore, genetics is a big part of understanding who we are. Our experiences matter a lot-our relationships with partners, children and friends, our occupations and interests. These experiences make life worth living and give it meaning. Relationships can also change our behavior, such as helping us to stop smoking or lose weight. They can affect our lifestyle by encouraging us to exercise, play sports and go to cultural events. But they don’t change who we are psychologically – our personality, our mental health and our cognitive abilities. Life experiences matter and can affect us profoundly, but they don’t make a difference in terms of who we are.

Cells

All living things are composed of cells, the smallest units of life [6]. One cell is about one tenth the diameter of a hair, and about three trillion cells are contained in the human body. Most body cells (the major exception being red blood cells) contain a smaller entity, called the nucleus, which is the organization center for the cell. Genetic information resides in the nucleus of the cell and is organized into physical structures called chromosomes. Chromosomes are generally transmitted as intact units from parent to child. Thus, markers residing close together on the same chromosome are inherited together; they exhibit genetic linkage. In contrast, markers on different chromosomes are generally inherited independently of one another. This principle is called random assortment. Markers that exhibit random assortment are not inherited together, or associated with each other in a given population, more often than might be expected by chance. Traits that show random assortment are said to be in linkage equilibrium. Conversely, markers that show genetic linkage, such as those close together on the same chromosome, are said to be in linkage disequilibrium; in a population, they are associated together more often than chance would predict.

Human cells contain 23 pairs of chromosomes. Each person has two copies of each chromosome; one comes from Dad and one from Mom. Thus, you inherit half of Dad’s genetic blueprint and half of Mom’s, which together provide you with a full complement. Small variations in an individual’s DNA allow for differentiation between people. One pair of the 23 chromosomes contains the information that determines gender. These chromosomes are given letters, rather than numbers, and are designated X and Y; males have one X and one Y chromosome (XY), and females have two X chromosomes (XX). Female eggs can contain only X chromosomes, while male sperm can contribute either an X or a Y chromosome. Therefore, gender is determined by the paternal component. The information contained in the sex chromosomes is so different that they even look different visually. Gender can be determined by DNA testing, and is sometimes a useful piece of information in case investigation.

Blueprint of life

DNA is sometimes referred to as the blueprint of life [6]. The information for the blueprint is encoded in the four chemical building blocks of DNA: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C). These units, called bases, are strung together in a linear fashion, like beads on a string. The specific sequence of the bases determines all the genetic attributes of a person. The properties of the DNA molecule are directly related to its physical structure. DNA in nature takes the form of a double helix. Two ribbon-like entities are entwined around each other and are held together by crossbars, like rungs of a ladder. Each rung is composed of two bases that have strong affinities for each other; collectively, these forces hold the DNA molecule together. Each rung of two bases is called a base pair. Only specific pairings between the four bases will match up and stick together. A always pairs with T, and G with C. This obligatory pairing, called complementary base pairing, is exploited in all DNA typing systems. When the double helix is intact, the DNA is called double-stranded; when the two halves of the helix come apart, either in nature or in the test tube (in vitro), the DNA is called single-stranded.

In nature, complementary base pairing is responsible for the ability to accurately replicate the DNA molecule, with its genetic information, and pass it on to the next generation. The double helix is unzipped by special enzymes, and new building blocks (nucleotides) are brought in. Each nucleotide contains one base attached to a piece of the backbone ribbon. Using each half of the original helix as a template, a second half is created, resulting in two molecules identical to the original. The order of bases in the new strands is specified by the existing strands. Each original base captures a complementary replacement to complete the base pair. Short segments of complementary singlestranded DNA also show a specific affinity for each other in vitro defined again by the specific base sequence. Under appropriate conditions, complementary DNA fragments will find each other and stick together. Technically, this is referred to as reannealing or hybridization. In the laboratory, it is crucial that the chemical conditions for hybridization be exact. These conditions, which are determined by scientific experimentation, are called stringency conditions. If the stringency is too high, no hybridization will occur; if the stringency is too low, reannealing will be less than exact and some DNA fragments might stick together even if they are not a perfect complementary match. If the sequence at a particular location in the genome is of interest, single-stranded fragments can be artificially synthesized to target that location. These single-stranded fragments of known sequence are variously called DNA probes or DNA primers, depending on their intended use.

Quantity

To develop a high-quality DNA profile it is important that the analyst first determines the quantity of DNA present in a sample [7]. If too much DNA is present, this can cause what is known as off-scale data in the final detection process of DNA analysis. Off-scale data tends to be littered with artifacts and extra peaks that make interpretation of the resulting profile difficult, if not impossible. As a result, most laboratories will not allow DNA analysts to use off-scale data. By contrast, if too little DNA is available, and then data retrieved at the detection process will be incomplete, often resulting in what is known as drop-out where information is missing and the result is an incomplete profile. Quantifying the DNA that is collected after extracting cells residing within the evidence addresses both of these issues. Once the amount of DNA is established, the DNA analyst can make any adjustments required before the amplification process. Samples with excess concentrations of DNA can be diluted; samples where the concentration of DNA is too low can either be concentrated or a new sample can be taken from the evidence so that it contains more of the biological material of interest. Even if this is not possible, quantification of the DNA available at this point provides an expectation to the DNA analyst of what can be expected in the final results. This data can even be used to guide investigators to submit additional pieces of evidence if the evidence submitted does not yield enough data to provide usable profiles.

However, simply performing DNA quantification is not sufficient. The methods employed must provide a specific degree of accuracy. If the processes are not accurate then it is no better than proceeding without quantifying DNA. The need for increasingly accurate techniques has influence the methods used for DNA quantification over the years. As new methods in processing DNA have become more sensitive, allowing DNA profile to be developed from smaller and smaller samples, there is now a need to determine how much DNA is contained in these very low-level samples. For some laboratories, being able to detect how much DNA is present in these samples is imperative because it will dictate the type of amplification process to be used, or, if the sample does not contain sufficient DNA, whether the analysis process should even continue.

DNA profile

When DNA was first used, human identification DNA was cut with a restriction enzyme, separated through an agarose gel, transferred to special paper, and detected with a radioactively labeled probe [8]. The probe bound to multiple locations in the DNA (creating a DNA fingerprint) or to single locations in the DNA (creating a DNA profile). This technique, known as Restriction Fragment Length Polymorphism (RFLP) analysis, was very labor intensive. Typically a case with a small quantity of DNA could take over a month to process, although cases with ample DNA could reveal information in under a week. While RFLPbased DNA profiling procedures were reliable and informative in determining biological relationships and identifications, they were also expensive, required skillful labor, did not lend them to automation, and the technique required at least 50 ng of fairly high molecular weight DNA to expect useful results. Over the years, the ability to obtain DNA profile results from samples with limited or degraded DNA were dramatically improved by looking at smaller areas of variation and making multiple copies through a technique called PCR (polymerase chain reaction). Today, all autosomal forensic DNA analysis and some of the sexlinked analyses are PCR based, amplifying STRs (short tandem repeat). Using this technology, human identifications can be reliably obtained from as little as 200 pg of nuclear DNA. STRs are smaller fragments of DNA with shorter repeat sequences than the DNA evaluated using the RFLP method and are therefore less influenced by degradation. Currently, DNA profiles for human identification typically contain 16–24 autosomal loci using a single, multiplexed amplification.

CONCLUSION

It is the basic molecule of inheritance and is responsible for the transmission of hereditary material and traits. In humans, these traits can range from hair color to a predisposition to certain diseases. During cell division, DNA is replicated and transmitted to offspring by reproduction. Origin studies can be based on both mitochondrial DNA, which we obtain only from the mother, and the male Y chromosome, which we obtain only from the father. The DNA of each person, their genome, is inherited from both parents. Maternal mitochondrial DNA, along with 23 chromosomes from each parent, combines to form the genome of the zygote, i.e. the fertilized egg. As a result, with some exceptions, e.g., red blood cells, most human cells contain 23 pairs of chromosomes, along with mitochondrial DNA inherited from the mother.

Received : 29 Oct 2021
Accepted : 13 Nov 2021
Published : 16 Nov 2021
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