Introduction. All living organisms are made up of cells. Genetic information is contained in DNA (deoxyribonucleic acid). This chemical is the main component of the chromosomes in the nucleus of cells. The cells of the human body have 46 chromosomes, actually 23 pairs. Of each pair, one of the chromosomes comes from the father and the other from the mother, and the two chromosomes of each pair are said to be homologous to each other. The DNA molecule is made up of repeating smaller chemical units called bases.
There are four bases identified by the letters A, T, C, and G, for adenine, thymine, cytosine, and guanine, respectively. Two strands of DNA pair up to form the double helix structure discovered by Watson and Crick in 1953. The bases of each strand face or pair with the bases of the other, always following the same rule: only T is located in front of A. and opposite C only G is located. Two strands that mate according to these rules are said to be complementary. Thus, a strand of the sequence TGAATTGCCGCCCGATAT will be complementary to a strand of the sequence ACTTAACGGCGGGCTATA. Base complementarity allows DNA to be replicated faithfully. For this, first the two strands are separated and each one of them serves as a template to manufacture, by means of cell enzymes, another complementary one and thus have two double helices identical to the original, that is, with the same sequence, the same information. Once duplicated, information is passed equally from one parent cell to its two daughter cells through mitosis, or cell division. Another type of cell division, called meiosis, occurs in the stem cells of gametes (sperm in men and eggs in women). In meiosis, the number of chromosomes is halved.
In humans, as in most mammals, the genetic information contained in the 23 chromosomes of a gamete (haploid cell) is approximately 3.3 billion bases in length. By having 46 chromosomes, the rest of the cells (called diploids) have twice as many. When we say that the human genome has been “sequenced”, what we mean is that the precise ordering of those 3.3 billion bases in the nucleus of a human gamete has been determined experimentally. All the cells of a multicellular organism, such as humans, have the same genetic information, because they all derive, by mitosis, from a single cell, the zygote, which is formed by the fusion of the spermatozoon with the ovum. There are exceptions to this rule: a special type of blood cell, lymphocytes, lose a small portion of DNA during the development of the individual, as part of a program that allows the adaptability of the immune system.
Genome and genes. We call the set of all the DNA of a cell of a species and the genes it contains a genome. In a strict sense, the human genome includes not only the DNA of the nucleus but also that of the mitochondria which, although only 16,000 bases long, is essential for cell function. Genes are segments of DNA capable of being transcribed – that is, copied – into an RNA (ribonucleic acid) molecule with the same sequence as the gene. Genes are not found juxtaposed along chromosomes, but rather scattered and separated at great distances by intergenic DNA sequences. Intergenic regions constitute 70% of the genome, while genes represent only 30%. It is estimated that the human genome has about 20,000 genes. These genes encode different types of RNA, among which are the so-called messenger RNAs, which in turn encode proteins. The other RNAs, those that are not messengers, receive the generic name of non-coding RNAs: they are not intermediaries between the gene and the protein, but rather fulfill functions in themselves. Among these are ribosomal, transfer, small nuclear RNAs, microRNAs, and ribozymes. Therefore, the definition according to which a gene is the segment of DNA that encodes a protein, is not strictly correct: many genes encode proteins, but not all. Each of the protein-coding genes has regions that will be represented in the mature mRNA interspersed by others whose sequences will not be represented there. The first regions are called exons, while the second are introns. While introns are non-coding, most exons are protein-coding regions of the genome. These regions constitute only 1.5% of the genome.
Each chromosome has many genes, and the position that each gene occupies along the chromosome is called a locus (Latin for place). Each gene then has its homologous copy at the equivalent locus on the other chromosome of the pair. Each of the two copies of the gene is called an allele.
Let’s say, then, that a human cell has two alleles for each of its 20,000 different genes. Not all genes are expressed (ie transcribed and translated) at the same time and in the same place. In a given tissue or cell type, a subset of the set of all genes is expressed. One of the key points in the regulation of gene expression is the control of transcription. This control is not only concerned with turning genes “on” or “off” (all or nothing effect), but also with regulating the amount of product (RNA or protein) of the “turned on” genes.
Surprisingly, 50% of our genome is made up of repeated sequences, mostly of viral origin. Many of these sequences, mostly located in intergenic regions and introns, correspond to the so-called mobile elements, or transposons, “jumping” segments of DNA, that is, they can be duplicated and inserted into other regions within the same genome.
Splicing. The enzyme that transcribes each gene makes a precursor RNA, called the primary transcript, which copies both exons and introns. Within the nucleus, an enzymatic system removes the introns from the primary transcript and joins its exons together. Finally, the mature messenger RNA without introns leaves the nucleus and reaches the cytoplasm where the translation process, carried out by the ribosomes, makes it possible to manufacture the corresponding protein. The same gene can give many protein variants. The mechanism is known as alternative splicing, and it consists in the fact that during splicing some exon, for example, can be alternatively included or excluded from the mature mRNA. It is estimated that there could be hundreds of thousands of different proteins encoded by the 20,000 genes in the human genome. This shows that the deciphering of the genome is not enough to understand in its real complexity the functioning of cells at the molecular level and that it will be necessary to accelerate the stage of the study of proteins, in what is called the post-genomic or proteomic era. . On the other hand, since the number of human genes is not significantly greater than that of a worm or a fly, it is estimated that the higher prevalence of alternative splicing in humans and other vertebrates explains its greater complexity.
Genotype and phenotype. The set of particular genetic information of an individual is called genotype. The genotype is essentially the DNA sequence. Everything that we “see” and that is not a DNA sequence is the phenotype (from the Greek, fainein, visible). The phenotype is both the macroscopic (shape, anatomy, physiology, pathology, and behavior) and the smallest (histology, biochemistry, and molecular structure). The phenotype is always the result of the interaction of a certain genotype with a certain environment, which is expressed with the formula:
PHENOTYPE = GENOTYPE + ENVIRONMENT
For some phenotypes, the influence of the genetic component is the majority or determinant and, consequently, the environmental one is virtually null. A good example is hereditary diseases such as cystic fibrosis, Huntington’s chorea, and muscular dystrophy: anyone who has inherited the mutated dystrophin gene will have the disease, no matter what environment they are in. In other phenotypes, the influence of the environmental component is the majority and that of the genetic component is negligible. Infectious diseases produced by contagion are an example.
For most phenotypic traits there is both a genetic and an environmental component. Many times we are sure of the existence of both but we do not know, or even know that it is difficult to estimate, the partial contribution of each one. Most diseases that are not strictly hereditary, such as cardiovascular diseases, cancers, high blood pressure, asthma, Alzheimer’s, Parkinson’s, and autoimmune diseases such as arthritis and lupus, may have a hereditary component, but they certainly do. not negligible environmental and, sometimes, preponderant. In many cases, molecular genetics has come to discover genes whose mutations cause a predisposition to said diseases, but that does not mean that whoever has that mutation will inevitably suffer from the disease.
Human behavior is also a consequence of the interaction of the genotype with the environment. However, except for a few inherited neurological disorders, a specific genetic influence has not been demonstrated. The alleged genetic basis of phenotypes as complex as intelligence, sexual orientation, criminality, artistic or sports abilities must be taken with a grain of salt and subjected to rigorous experimental analysis in each particular case. Otherwise, there is a risk of falling into genetic determinism, which, far from being a biological law, is an instrument of discrimination and socioeconomic domination.
Knowledge of the genome does not authorize anyone to stigmatize people as an irreversible result of what their genes order. Genes tell us that we can speak, but not what language; that we can love, but not whom; that we can enjoy music, but not which one.
The different types of intelligence, abilities, affections and our actions are results of the acculturation process, which is not registered in any gene and, instead, is strongly influenced by the family, social and economic environment in which we live.
The inherited and the acquired. To refer to the inherited or acquired character of a trait, it is very important to differentiate three biological concepts: congenital, genetic and heritable. Congenital is what can happen to the embryo or fetus during intrauterine life, whether or not it is caused by gene mutations (ie, genetic) and whether or not those possible mutations are inherited from either parent (inheritable). Thus, a defect or congenital characteristic of an individual can come from situations experienced by the mother during pregnancy or simply from uncontrollable phenomena known as “noise” of embryonic development. In this case, it will affect the life of that individual but will not be transmitted to her offspring.
A genetic characteristic is caused by alterations in the genes, but it is not necessarily heritable. For example, a skin tumor has a genetic origin because it is produced by mutations in the genes of a skin cell. But this change in the genes of that cell is not transmitted to the offspring because it does not affect the germ cells (eggs or sperm). It means that it is genetic, but it is not heritable.
Finally, what is heritable, which is always genetic, is the only thing that could be taken into account to support a purely deterministic theory. Genetic alterations are transmitted by certain laws from parents to children.
When, without evidence, human behavior or intellectual capacities are attributed to genes, and it is assumed that the variants of these genes are distributed asymmetrically in different human groups, they end up postulating deterministic hypotheses, such as, for example, that certain groups have a ceiling. intellectual and that it is not “worth it” to invest money in education for them because they are “genetically” limited.
Epigenetics. There are mechanisms to control the activity of genes that do not affect their information or base sequence, but rather modify their switching on and off in a more or less stable manner.
We understand that a gene is turned on when its transcription is active and, consequently, the manufacture of the corresponding protein. Conversely, a gene is turned off when it is not being transcribed.
A gene can switch from being on to off and back again at different times in the life of a cell, in different cell types in the same individual, and in response to external signals. The control mechanisms to which we refer are part of the field of epigenetics and include the addition of chemical groups to the bases of DNA and/or to the amino acids of histones. Histones are proteins that associate with the DNA of genes. The association between DNA and histones is what is known as chromatin, and chromatin is the main ingredient of chromosomes.
It depends on which chemical groups are added by certain enzymes in the cell to the DNA or histones of a given gene, to determine whether that gene is to be turned off or on. For example, if the DNA of a given gene is heavily methylated, that gene is most likely to remain off. The same can happen if certain histone amino acids are methylated, and the opposite if those same amino acids are acetylated.
Epigenetic modifications of a given gene can be inherited from a mother cell to its daughter cells, so that the daughters inherit not only the gene information (base sequence) but the expression state (on or off) of that gene. This is very important in ensuring that all cells in an organ (eg, the liver) not only have the same information, but also the same expression pattern of their genes and are differentiated in the same way. Epigenetics can then provide an additional level of heritability to that of genetics. However, faced with the expectation that epigenetic phenomena explain Lamarckism, that is, an inheritance of phenotypically acquired characters, we must consider the following:
Epigenetics. There are mechanisms to control the activity of genes that do not affect their information or base sequence, but rather modify their switching on and off in a more or less stable manner.
We understand that a gene is turned on when its transcription is active and, consequently, the manufacture of the corresponding protein. Conversely, a gene is turned off when it is not being transcribed.
A gene can switch from being on to off and back again at different times in the life of a cell, in different cell types in the same individual, and in response to external signals. The control mechanisms to which we refer are part of the field of epigenetics and include the addition of chemical groups to the bases of DNA and/or to the amino acids of histones. Histones are proteins that associate with the DNA of genes. The association between DNA and histones is what is known as chromatin, and chromatin is the main ingredient of chromosomes.
It depends on which chemical groups are added by certain enzymes in the cell to the DNA or histones of a given gene, to determine whether that gene is to be turned off or on. For example, if the DNA of a given gene is heavily methylated, that gene is most likely to remain off. The same can happen if certain histone amino acids are methylated, and the opposite if those same amino acids are acetylated.
Epigenetic modifications of a given gene can be inherited from a mother cell to its daughter cells, so that the daughters inherit not only the gene information (base sequence) but the expression state (on or off) of that gene. This is very important in ensuring that all cells in an organ (eg, the liver) not only have the same information, but also the same expression pattern of their genes and are differentiated in the same way. Epigenetics can then provide an additional level of heritability to that of genetics. However, faced with the expectation that epigenetic phenomena explain Lamarckism, that is, an inheritance of phenotypically acquired characters, we must consider the following:
- Epigenetic changes are part of environmental changes.
- Although the inheritance of epigenetic changes from a cell to its daughters has been corroborated, in very few cases of plants and in many fewer of animals, it has been possible to corroborate transgenerational inheritance.
- Any presumed transgenerational inheritance of an epigenetic change dictates the need for that change to occur in gamete stem cells. In this sense, it would be difficult for an epigenetic change in the DNA of certain neurons in the brain of an animal, which determines a behavior pattern, to be transmitted to its children, since this occurs in different cells and far from the gametes.
- The changes are usually reversed if the external stimulus that generated them does not persist. That is why it is said that epigenetics is a type of “soft” inheritance as opposed to genetics, which would be a “hard” inheritance.
Genome, genomic variability and breeds. We can define a species as a group of individuals capable of giving fertile offspring by sexual reproduction. Individuals belonging to the same species often have genetic differences. This is so because, although the individual presents two alleles for each gene –two variants of the same gene–, the number of alleles of a gene existing in the species as a whole is generally greater than two. A gene can have dozens of different alleles, but in each individual there will only be two of them. A race is a subpopulation of individuals of a species that has a high genetic homogeneity, that is to say that the individuals that compose it share many more alleles with each other than with any other individual of the same species, but of another race.
Comparisons of DNA sequences between humans indicate that major genetic differences, if they exist, occur between individuals and not between populations. In simpler terms, for example, a Caucasian (white) person from Europe may share many more allelic variants with an Asian or African person than with another European of the same skin color. Two black Africans can be far more genetically distant from each other than either of them can be from a white. This means, for example, that in many cases the histocompatibility (that is, how compatible their organs and tissues are) between a black and a white is greater than between two individuals of the same “race” and, as a consequence, a black is more apt than a target to donate an organ transplant to another target. Molecular studies by geneticist Svante Paabo confirm that human races do not exist. The same concept was expressed in a simple and elegant way by the Brazilian geneticist Sérgio Pena: “It is not that we are all the same, but that we are all equally different”.
One of the sources of intraspecific variability are the changes of a base in the same position between different individuals. These changes are called SNPs (pronounced snips), for single nucleotide polymorphisms. Although SNPs are not evenly distributed throughout our genome, it is estimated that one SNP appears on average every thousand bases of sequence. This indicates that the genome of our species, Homo sapiens, is highly homogeneous with a sequence similarity of 99.9%. Sequence similarity between humans and chimpanzees is around 98%. However, there are differences, both between humans and between humans and chimpanzees, that are not due to SNPs but to variations in the number of copies of a given segment of DNA within the same genome, which can raise the differences between individuals to levels 5-6%.
It is not yet clear how copy number variations contribute to the phenotype of humans.
Human genome heritage of humanity. On November 11, 1997, UNESCO unanimously approved the Universal Declaration on the Human Genome and Human Rights. This Declaration defines that the human genome is the fundamental basis for the unity of all members of the human family and for the recognition of their intrinsic dignity and diversity. In a symbolic sense, the human genome is the patrimony of humanity and that each individual has the right to respect for their dignity and rights, whatever their genetic characteristics, respecting the unique character of each one and their diversity.
