Genes as the Unit of Heredity
Genes exist in pairs within an organism, with one of each pair inherited from each parent.
Describe the structure of a gene and how offspring inherit genes from each parent
- A gene is a stretch of DNA that helps to control the development and function of all organs and working systems in the body.
- Genes are passed from parent to offspring; the combination of these genes affects all aspects of the human body, from eye and hair color to how well the liver can process toxins.
- A human will inherit 23 chromosomes from its mother and 23 from its father; together, these form 23 pairs of chromosomes that direct the inherited characteristics of the individual.
- If the two copies of a gene inherited from each parent are the same, that individual is said to be homozygous for the gene; if the two copies inherited from each parent are different, that individual is said to be heterozygous for the gene.
- gene: a unit of heredity; the functional units of chromosomes that determine specific characteristics by coding for specific proteins
- chromosome: a structure in the cell nucleus that contains DNA, histone protein, and other structural proteins
- genetics: the branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA
Pairs of Unit Factors, or Genes
Mendel proposed that paired unit factors of heredity were transmitted faithfully from generation to generation by the dissociation and reassociation of paired factors during gametogenesis and fertilization, respectively. After he crossed peas with contrasting traits and found that the recessive trait resurfaced in the F2 generation, Mendel deduced that hereditary factors must be inherited as discrete units. This finding contradicted the belief at that time that parental traits were blended in the offspring.
A gene is made up of short sections of DNA that are contained on a chromosome within the nucleus of a cell. Genes control the development and function of all organs and all working systems in the body. A gene has a certain influence on how the cell works; the same gene in many different cells determines a certain physical or biochemical feature of the whole body (e.g., eye color or reproductive functions). All human cells hold approximately 21,000 different genes.
Genetics is the science of the way traits are passed from parent to offspring. For all forms of life, continuity of the species depends upon the genetic code being passed from parent to offspring. Evolution by natural selection is dependent on traits being heritable. Genetics is very important in human physiology because all attributes of the human body are affected by a person’s genetic code. It can be as simple as eye color, height, or hair color. Or it can be as complex as how well your liver processes toxins, whether you will be prone to heart disease or breast cancer, and whether you will be color blind.
Genetic inheritance begins at the time of conception. You inherited 23 chromosomes from your mother and 23 from your father. Together they form 22 pairs of autosomal chromosomes and a pair of sex chromosomes (either XX if you are female, or XY if you are male). Homologous chromosomes have the same genes in the same positions, but may have different alleles (varieties) of those genes. There can be many alleles of a gene within a population, but an individual within that population only has two copies and can be homozygous (both copies the same) or heterozygous (the two copies are different) for any given gene.
Phenotypes and Genotypes
The observable traits expressed by an organism are referred to as its phenotype and its underlying genetic makeup is called its genotype.
Distinguish between the phenotype and the genotype of an organism
- Mendel used pea plants with seven distinct traits or phenotypes to determine the pattern of inheritance and the underlying genotypes.
- Mendel found that crossing two purebred pea plants which expressed different traits resulted in an F1 generation where all the pea plants expressed the same trait or phenotype.
- When Mendel allowed the F1 plants to self-fertilize, the F2 generation showed two different phenotypes, indicating that the F1 plants had different genotypes.
- phenotype: the appearance of an organism based on a multifactorial combination of genetic traits and environmental factors, especially used in pedigrees
- genotype: the combination of alleles, situated on corresponding chromosomes, that determines a specific trait of an individual, such as “Aa” or “aa”
Phenotypes and Genotypes
The observable traits expressed by an organism are referred to as its phenotype. An organism’s underlying genetic makeup, consisting of both physically visible and non-expressed alleles, is called its genotype. Johann Gregor Mendel’s (1822–1884) hybridization experiments demonstrate the difference between phenotype and genotype.
Mendel crossed or mated two true-breeding (self-pollinating) garden peas, Pisum saivum, by manually transferring pollen from the anther of a mature pea plant of one variety to the stigma of a separate mature pea plant of the second variety. Plants used in first-generation crosses were called P0, or parental generation one, plants. Mendel collected the seeds belonging to the P0 plants that resulted from each cross and grew them the following season. These offspring were called the F1, or the first filial (filial = offspring, daughter or son), generation. Once Mendel examined the characteristics in the F1 generation of plants, he allowed them to self-fertilize naturally. He then collected and grew the seeds from the F1 plants to produce the F2, or second filial, generation.
When true-breeding plants in which one parent had white flowers and one had violet flowers were cross-fertilized, all of the F1 hybrid offspring had violet flowers. That is, the hybrid offspring were phenotypically identical to the true-breeding parent with violet flowers. However, we know that the allele donated by the parent with white flowers was not simply lost because it reappeared in some of the F2 offspring. Therefore, the F1 plants must have been genotypically different from the parent with violet flowers.
In his 1865 publication, Mendel reported the results of his crosses involving seven different phenotypes, each with two contrasting traits. A trait is defined as a variation in the physical appearance of a heritable characteristic. The characteristics included plant height, seed texture, seed color, flower color, pea pod size, pea pod color, and flower position. To fully examine each characteristic, Mendel generated large numbers of F1 and F2 plants, reporting results from 19,959 F2 plants alone. His findings were consistent. First, Mendel confirmed that he had plants that bred true for white or violet flower color. Regardless of how many generations Mendel examined, all self-crossed offspring of parents with white flowers had white flowers, and all self-crossed offspring of parents with violet flowers had violet flowers. In addition, Mendel confirmed that, other than flower color, the pea plants were physically identical.
The Punnett Square Approach for a Monohybrid Cross
A Punnett square applies the rules of probability to predict the possible outcomes of a monohybrid cross and their expected frequencies.
Describe the Punnett square approach to a monohybrid cross
- Fertilization between two true-breeding parents that differ in only one characteristic is called a monohybrid cross.
- For a monohybrid cross of two true-breeding parents, each parent contributes one type of allele resulting in all of the offspring with the same genotype.
- A test cross is a way to determine whether an organism that expressed a dominant trait was a heterozygote or a homozygote.
- monohybrid: a hybrid between two species that only have a difference of one gene
- homozygous: of an organism in which both copies of a given gene have the same allele
- heterozygous: of an organism which has two different alleles of a given gene
- Punnett square: a graphical representation used to determine the probability of an offspring expressing a particular genotype
Punnett Square Approach to a Monohybrid Cross
When fertilization occurs between two true-breeding parents that differ in only one characteristic, the process is called a monohybrid cross, and the resulting offspring are monohybrids. Mendel performed seven monohybrid crosses involving contrasting traits for each characteristic. On the basis of his results in F1 and F2 generations, Mendel postulated that each parent in the monohybrid cross contributed one of two paired unit factors to each offspring and that every possible combination of unit factors was equally likely.
To demonstrate a monohybrid cross, consider the case of true-breeding pea plants with yellow versus green pea seeds. The dominant seed color is yellow; therefore, the parental genotypes were YY ( homozygous dominant) for the plants with yellow seeds and yy (homozygous recessive ) for the plants with green seeds, respectively. A Punnett square, devised by the British geneticist Reginald Punnett, can be drawn that applies the rules of probability to predict the possible outcomes of a genetic cross or mating and their expected frequencies.To prepare a Punnett square, all possible combinations of the parental alleles are listed along the top (for one parent) and side (for the other parent) of a grid, representing their meiotic segregation into haploid gametes. Then the combinations of egg and sperm are made in the boxes in the table to show which alleles are combining. Each box then represents the diploid genotype of a zygote, or fertilized egg, that could result from this mating. Because each possibility is equally likely, genotypic ratios can be determined from a Punnett square. If the pattern of inheritance (dominant or recessive) is known, the phenotypic ratios can be inferred as well. For a monohybrid cross of two true-breeding parents, each parent contributes one type of allele. In this case, only one genotype is possible. All offspring are Yy and have yellow seeds.
A self-cross of one of the Yy heterozygous offspring can be represented in a 2 × 2 Punnett square because each parent can donate one of two different alleles. Therefore, the offspring can potentially have one of four allele combinations: YY, Yy, yY, or yy. Notice that there are two ways to obtain the Yy genotype: a Y from the egg and a y from the sperm, or a y from the egg and a Y from the sperm. Both of these possibilities must be counted. Recall that Mendel’s pea-plant characteristics behaved in the same way in reciprocal crosses. Therefore, the two possible heterozygous combinations produce offspring that are genotypically and phenotypically identical despite their dominant and recessive alleles deriving from different parents. They are grouped together. Because fertilization is a random event, we expect each combination to be equally likely and for the offspring to exhibit a ratio of YY:Yy:yy genotypes of 1:2:1. Furthermore, because the YY and Yy offspring have yellow seeds and are phenotypically identical, applying the sum rule of probability, we expect the offspring to exhibit a phenotypic ratio of 3 yellow:1 green. Indeed, working with large sample sizes, Mendel observed approximately this ratio in every F2 generation resulting from crosses for individual traits.
Beyond predicting the offspring of a cross between known homozygous or heterozygous parents, Mendel also developed a way to determine whether an organism that expressed a dominant trait was a heterozygote or a homozygote. Called the test cross, this technique is still used by plant and animal breeders. In a test cross, the dominant-expressing organism is crossed with an organism that is homozygous recessive for the same characteristic. If the dominant-expressing organism is a homozygote, then all F1 offspring will be heterozygotes expressing the dominant trait. Alternatively, if the dominant expressing organism is a heterozygote, the F1 offspring will exhibit a 1:1 ratio of heterozygotes and recessive homozygotes. The test cross further validates Mendel’s postulate that pairs of unit factors segregate equally.
Alternatives to Dominance and Recessiveness
With the inclusion of incomplete dominance, codominance, multiple alleles, and mutant alleles, the inheritance of traits is complex process.
Discuss incomplete dominance, codominance, and multiple alleles as alternatives to dominance and recessiveness
- Incomplete dominance is the expression of two contrasting alleles such that the individual displays an intermediate phenotype.
- Codominance is a variation on incomplete dominance in which both alleles for the same characteristic are simultaneously expressed in the heterozygote.
- Diploid organisms can only have two alleles for a given gene; however, multiple alleles may exist at the population level such that many combinations of two alleles are observed.
- The complete dominance of a wild-type phenotype over all other mutants often occurs as an effect of “dosage” of a specific gene product: the wild-type allele supplies the correct amount of gene product whereas the mutant alleles cannot.
- One mutant allele can also be dominant over all other phenotypes, including the wild type.
- allele: one of a number of alternative forms of the same gene occupying a given position on a chromosome
- incomplete dominance: a condition in which the phenotype of the heterozygous genotype is distinct from and often intermediate to the phenotypes of the homozygous genotypes
- codominance: a condition in which both alleles of a gene pair in a heterozygote are fully expressed, with neither one being dominant or recessive to the other
Alternatives to Dominance and Recessiveness
Mendel’s experiments with pea plants suggested that: (1) two “units” or alleles exist for every gene; (2) alleles maintain their integrity in each generation (no blending); and (3) in the presence of the dominant allele, the recessive allele is hidden and makes no contribution to the phenotype. Therefore, recessive alleles can be “carried” and not expressed by individuals. Such heterozygous individuals are sometimes referred to as “carriers.” Further genetic studies in other plants and animals have shown that much more complexity exists, but that the fundamental principles of Mendelian genetics still hold true.
Mendel’s results, that traits are inherited as dominant and recessive pairs, contradicted the view at that time that offspring exhibited a blend of their parents’ traits. However, the heterozygote phenotype occasionally does appear to be intermediate between the two parents. For example, in the snapdragon, Antirrhinum majus, a cross between a homozygous parent with white flowers (CWCW) and a homozygous parent with red flowers (CRCR) will produce offspring with pink flowers (CRCW). This pattern of inheritance is described as incomplete dominance, denoting the expression of two contrasting alleles such that the individual displays an intermediate phenotype. The allele for red flowers is incompletely dominant over the allele for white flowers. However, the results of a heterozygote self-cross can still be predicted, just as with Mendelian dominant and recessive crosses. In this case, the genotypic ratio would be 1 CRCR:2 CRCW:1 CWCW, and the phenotypic ratio would be 1:2:1 for red:pink:white.
A variation on incomplete dominance is codominance, in which both alleles for the same characteristic are simultaneously expressed in the heterozygote. An example of codominance is the MN blood groups of humans. The M and N alleles are expressed in the form of an M or N antigen present on the surface of red blood cells. Homozygotes (LMLM and LNLN) express either the M or the N allele, and heterozygotes (LMLN) express both alleles equally. In a self-cross between heterozygotes expressing a codominant trait, the three possible offspring genotypes are phenotypically distinct. However, the 1:2:1 genotypic ratio characteristic of a Mendelian monohybrid cross still applies.
Mendel implied that only two alleles, one dominant and one recessive, could exist for a given gene. We now know that this is an oversimplification. Although individual humans (and all diploid organisms) can only have two alleles for a given gene, multiple alleles may exist at the population level such that many combinations of two alleles are observed. Note that when many alleles exist for the same gene, the convention is to denote the most common phenotype or genotype among wild animals as the wild type (often abbreviated “+”); this is considered the standard or norm. All other phenotypes or genotypes are considered variants of this standard, meaning that they deviate from the wild type. The variant may be recessive or dominant to the wild-type allele. An example of multiple alleles is coat color in rabbits. Here, four alleles exist for the c gene. The wild-type version, C+C+, is expressed as brown fur. The chinchilla phenotype, cchcch, is expressed as black-tipped white fur. The Himalayan phenotype, chch, has black fur on the extremities and white fur elsewhere. Finally, the albino, or “colorless” phenotype, cc, is expressed as white fur. In cases of multiple alleles, dominance hierarchies can exist. In this case, the wild-type allele is dominant over all the others, chinchilla is incompletely dominant over Himalayan and albino, and Himalayan is dominant over albino. This hierarchy, or allelic series, was revealed by observing the phenotypes of each possible heterozygote offspring.
The complete dominance of a wild-type phenotype over all other mutants often occurs as an effect of “dosage” of a specific gene product, such that the wild-type allele supplies the correct amount of gene product whereas the mutant alleles cannot. For the allelic series in rabbits, the wild-type allele may supply a given dosage of fur pigment, whereas the mutants supply a lesser dosage or none at all. Alternatively, one mutant allele can be dominant over all other phenotypes, including the wild type. This may occur when the mutant allele somehow interferes with the genetic message so that even a heterozygote with one wild-type allele copy expresses the mutant phenotype. One way in which the mutant allele can interfere is by enhancing the function of the wild-type gene product or changing its distribution in the body. One example of this is the Antennapedia mutation in Drosophila. In this case, the mutant allele expands the distribution of the gene product; as a result, the Antennapedia heterozygote develops legs on its head where its antennae should be.
A gene present on one of the sex chromosomes (X or Y in mammals) is a sex-linked trait because its expression depends on the sex of the individual.
Distinguish between sex-linked traits and other forms of inheritance
- In mammals, females have a homologous pair of X chromosomes, whereas males have an XY chromosome pair.
- The Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, but the Y is much shorter and contains fewer genes.
- Males are said to be hemizygous because they have only one allele for any X-linked characteristic; males will exhibit the trait of any gene on the X-chromosome regardless of dominance and recessiveness.
- Most sex-linked traits are actually X-linked, such as eye color in Drosophila or color blindness in humans.
- hemizygous: Having some single copies of genes in an otherwise diploid cell or organism.
- X-linked: Associated with the X chromosome.
- carrier: A person or animal that transmits a disease to others without itself contracting the disease.
- sex chromosomes: A chromosome involved with determining the sex of an organism, typically one of two kinds.
In humans, as well as in many other animals and some plants, the sex of the individual is determined by sex chromosomes. However, there are other sex determination systems in nature. For example, temperature-dependent sex determination is relatively common,
and there are many other types of environmental sex determination. Some species, such as some snails, practice sex change adults start out male, then become female. In tropical clown fish, the dominant individual in a group becomes female while the others are male.
The sex chromosomes are one pair of non-homologous chromosomes. Until now, we have only considered inheritance patterns among non-sex chromosomes, or autosomes. In addition to 22 homologous pairs of autosomes, human females have a homologous pair of X chromosomes, whereas human males have an XY chromosome pair. Although the Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, the Y chromosome is much shorter and contains many fewer genes. When a gene being examined is present on the X chromosome, but not on the Y chromosome, it is said to be X-linked.
Insects also follow an XY sex-determination pattern and like humans, Drosophila males have an XY chromosome pair and females are XX. Eye color in Drosophila was one of the first X-linked traits to be identified, and Thomas Hunt Morgan mapped this trait to the X chromosome in 1910.
In fruit flies, the wild-type eye color is red (XW) and is dominant to white eye color (Xw). Because this eye-color gene is located on the X chromosome only, reciprocal crosses do not produce the same offspring ratios. Males are said to be hemizygous, because they have only one allele for any X-linked characteristic. Hemizygosity makes the descriptions of dominance and recessiveness irrelevant for XY males because each male only has one copy of the gene. Drosophila males lack a second allele copy on the Y chromosome; their genotype can only be XWY or XwY. In contrast, females have two allele copies of this gene and can be XWXW, XWXw, or XwXw.
In an X-linked cross, the genotypes of F1 and F2 offspring depend on whether the recessive trait was expressed by the male or the female in the P1 generation. With regard to Drosophila eye color, when the P1 male expresses the white-eye phenotype and the female is homozygous red-eyed, all members of the F1 generation exhibit red eyes. The F1 females are heterozygous (XWXw), and the males are all XWY, having received their X chromosome from the homozygous dominant P1 female and their Y chromosome from the P1 male.
A subsequent cross between the XWXw female and the XWY male would produce only red-eyed females (with XWXW or XWXw genotypes) and both red- and white-eyed males (with XWY or XwY genotypes). Now, consider a cross between a homozygous white-eyed female and a male with red eyes. The F1 generation would exhibit only heterozygous red-eyed females (XWXw) and only white-eyed males (XwY). Half of the F2 females would be red-eyed (XWXw) and half would be white-eyed (XwXw). Similarly, half of the F2 males would be red-eyed (XWY) and half would be white-eyed (XwY).
X-Linked Recessive Disorders in Humans
Sex-linkage studies provided the fundamentals for understanding X-linked recessive disorders in humans, which include red-green color blindness and Types A and B hemophilia. Because human males need to inherit only one recessive mutant X allele to be affected, X-linked disorders are disproportionately observed in males. Females must inherit recessive X-linked alleles from both of their parents in order to express the trait.
When they inherit one recessive X-linked mutant allele and one dominant X-linked wild-type allele, they are carriers of the trait and are typically unaffected. Carrier females can manifest mild forms of the trait due to the inactivation of the dominant allele located on one of the X chromosomes. However, female carriers can contribute the trait to their sons, resulting in the son exhibiting the trait, or they can contribute the recessive allele to their daughters, resulting in the daughters being carriers of the trait. Although some Y-linked recessive disorders exist, typically they are associated with infertility in males and are, therefore, not transmitted to subsequent generations.
Lethal Inheritance Patterns
Inheriting two copies of mutated genes that are nonfunctional can have lethal consequences.
Describe recessive and dominant lethal inheritance patterns
- An inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype is referred to as recessive lethal.
- The dominant lethal inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote; this allele can only be transmitted if the lethality phenotype occurs after reproductive age.
- Dominant lethal alleles are very rare because the allele only lasts one generation and is, therefore, not usually transmitted.
- In the case where dominant lethal alleles might not be expressed until adulthood, the allele may be unknowingly passed on, resulting in a delayed death in both generations.
- mutation: any heritable change of the base-pair sequence of genetic material
- recessive lethal: an inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype
- dominant lethal: an inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote; this allele can only be transmitted if the lethality phenotype occurs after reproductive age
Lethal Inheritance Patterns
A large proportion of genes in an individual’s genome are essential for survival. Occasionally, a nonfunctional allele for an essential gene can arise by mutation and be transmitted in a population as long as individuals with this allele also have a wild-type, functional copy. The wild-type allele functions at a capacity sufficient to sustain life and is, therefore, considered to be dominant over the nonfunctional allele. However, consider two heterozygous parents that have a genotype of wild-type/nonfunctional mutant for a hypothetical essential gene. In one quarter of their offspring, we would expect to observe individuals that are homozygous recessive for the nonfunctional allele. Because the gene is essential, these individuals might fail to develop past fertilization, die in utero, or die later in life, depending on what life stage requires this gene. An inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype is referred to as recessive lethal.
For crosses between heterozygous individuals with a recessive lethal allele that causes death before birth when homozygous, only wild-type homozygotes and heterozygotes would be observed. The genotypic ratio would therefore be 2:1. In other instances, the recessive lethal allele might also exhibit a dominant (but not lethal) phenotype in the heterozygote. For instance, the recessive lethal Curly allele in Drosophila affects wing shape in the heterozygote form, but is lethal in the homozygote.
Dominant Lethal Alleles
A single copy of the wild-type allele is not always sufficient for normal functioning or even survival. The dominant lethal inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote; this allele can only be transmitted if the lethality phenotype occurs after reproductive age. Individuals with mutations that result in dominant lethal alleles fail to survive even in the heterozygote form. Dominant lethal alleles are very rare because, as you might expect, the allele only lasts one generation and is not transmitted. However, just as the recessive lethal allele might not immediately manifest the phenotype of death, dominant lethal alleles also might not be expressed until adulthood. Once the individual reaches reproductive age, the allele may be unknowingly passed on, resulting in a delayed death in both generations. An example of this in humans is Huntington’s disease in which the nervous system gradually wastes away. People who are heterozygous for the dominant Huntington allele (Hh) will inevitably develop the fatal disease. However, the onset of Huntington’s disease may not occur until age 40, at which point the afflicted persons may have already passed the allele to 50 percent of their offspring.