Evolution is caused by changes in the genetic composition of populations. In the field of population genetics, scientists model this process as changes in the frequency of alleles at individual genetic loci. This simple representation of how evolution occurs dates to Gregor Mendel’s analysis of trait inheritance patterns in pea plants, first presented in 1865. Mendel determined, using rigorous collection of data, that noticeable traits are controlled by two alleles of each gene (he called them factors), one from each parent. In addition, he concluded that some alleles are dominant to others (deemed recessive). Interestingly, Mendel’s data was not appreciated until 1900, probably in part because his approach to the study of inheritance was so divergent from his predecessors. Even after his brilliant experiments were rediscovered, it took 30 additional years for Mendelian inheritance to become integrated with evolutionary theory and to gain universal acceptance.
Why was such a seemingly clear and straightforward process dormant for so long and then the center of controversy for decades? One key to the controversy is that we rarely see the clear patterns of inheritance described by Mendel. Animal and plant breeders most often see evidence for what was described as blending inheritance, or offspring whose phenotypes are intermediate between those of their parents, rather than the discrete segregation of traits into well-defined categories, like smooth versus wrinkled peas or red versus white flowers. Mendelian inheritance thus did not align well with practical experience and it took decades to reconcile the two. Additionally, there are now known to be modes of inheritance that, at first glance, appear to violate Mendel’s laws. Deeper investigations into genetics using molecular biology have effectively characterized these novel modes of inheritance. The new information does not invalidate Mendel’s findings, however, it simply enhances his model.
There are three main phenomena: epistasis, pleiotropy, and sex-linkage that appear to violate the basic dominance and recessivity rules of Mendelian inheritance. Epistasis occurs when two or more genes or alleles interact to affect a phenotype. A function of one gene product may be required to allow another gene to be expressed or to function normally. On the other hand, pleiotropy occurs when one gene controls the expression of multiple phenotypes in an individual. For example, a large proportion of cats with white fur and blue eyes are deaf 1. Pleiotropy is often antagonistic, meaning that the same gene causes beneficial changes in one facet of an individual’s phenotype while at the same time causing damaging changes in some other aspect of an individual’s phenotype. Antagonistic pleiotropy is seen as a tradeoff or constraint on evolution, as proposed by George C. Williams. For example, the age specific decline in performance, or senescence, is thought to be a pleiotropic trait controlled by the same genes that increase early-life fecundity2,3.
Sex linkage is another phenomenon discovered as a counter-example to basic Mendelian inheritance. In many organisms, pairs of sex chromosomes determine gender. In humans and many mammals, XX individuals are female while XY individuals are male. Male offspring inherit an X from their mother and a Y from their father; females inherit an X from their mother and an X from their father. In most species, the ratio of males to females at birth under “normal” environmental conditions is 1:1. Y-chromosomes undergo little recombination with X chromosomes during meiosis, due to the fact that, over evolutionary time, they have lost a substantial number of genes. Interestingly, there are only 16 genes shared by the human X and Y chromosomes4.
For X-linked traits (traits encoded by genes on the X chromosome) females can be homozygous (having two copies of the same allele) or heterozygous (having two different alleles). If the trait is recessive, females will only show the phenotype for the trait if they are homozygous. Heterozygous females “carry” the recessive allele, but do not express the phenotype of that allele. Statistically speaking, half of her sons will inherit this recessive allele and all will express the phenotype because males have only one X chromosome.
A commonly used example of an X-linked phenotype is hemophilia, a disease that prevents the synthesis of blood clotting proteins. If a female is heterozygous (is a carrier, genotype XH Xh) mates with a normal male (genotype XH Y), 50% of the sons will be affected. If the female was instead homozygous for the trait (genotype Xh Xh ), none of her daughters would be hemophiliacs but 100% of her sons would be. The differential phenotypic ratios seen in sons and daughters appears to violate Mendel’s laws, yet Mendel’s first law still applies; each offspring has a 50% chance of inheriting an X-chromosome carrying the hemophilia allele from a heterozygous mother5.
Like humans, the fruit fly Drosophila melanogaster has an XY-sex determination system. D. melanogaster make excellent laboratory organisms because they are easy to keep, breed, and manipulate. Wild-type flies have what is considered normal body morphology and red eyes. Many lines are readily available for purchase, including some with mutations resulting in flies without eyes, with eyes of varying color, or missing wings. These organisms can be used to study or demonstrate both Mendelian and non-Mendelian inheritance patterns. In fact, 1933 Nobel Prize winner, Thomas Hunt Morgan, first noticed that some genes are sex-linked using this system6.
An inheritance is something passed from one generation to another. In some contexts, this means stuff like houses and money. In the context of biology, however, the study of genes and how they are inherited, is called genetics. Gregor Mendel is credited with being the father of modern genetics. His work is responsible for our understanding of how noticeable physical traits, or phenotypes, are passed from one generation to the next. Famously, he studied such traits in pea plants.
The pieces of information controlling those phenotypes are called genes. As there are two copies of each gene, known as alleles, we can represent these as letters. Here, we'll use the letter P. This is the first step of Mendel's famous experiment on pea flower coloration, represented here, using a tool called the Punnett square. Mendel found that when he crossed purple flowers with white ones, all of the progeny, or the first-generation plants, had purple flowers. This is because the purple color is dominant, shown using uppercase P. And carrying even one dominant allele means the phenotype will be expressed. But interestingly, when these purple flowers were crossed again, 1/4 of them were white. Where were the white flowers in the first generation? All of the first generation of purple-flowered plants were heterozygous, meaning that they had one capital purple P and one lowercase, or white, P. When they passed on their alleles in the F2 generation cross, this meant that 1/4 of the offspring received two small P alleles, and so, expressed the white phenotype. Mendel didn't have the Punnett square tool to use, he had to figure all of this out by keeping track of thousands of plants, and then noticing patterns in their numbers.
From this evidence, and a lot more, we now know that genes are also present in two copies in other organisms, too, like humans, and flies. In following up on Mendel's work, several scientists found that not all inheritance patterns followed the simple, basic model that Mendel proposed. For example, in hemophilia, a genetic clotting disorder, unaffected mothers were capable of transmitting the disease to their male children. The reason behind this lies in chromosomes, which were studied by Thomas Hunt Morgan, using his famous fruit flies, Drosophila. Because of Morgan and others, we now know that chromosomes are long strands of DNA that typically exist in pairs. Here, we can see that Drosophila has four of them. These chromosomes have genes on them for different traits, much like how a cookbook contains lots of different recipes. Nowadays, using modern microscopy, we can actually see these chromosomes and even organize them. The product of this process is called a karyotype. Here, you can see a human one. In both humans and flies, there are autosomes, and sex chromosomes. Humans, like flies, have X and Y chromosomes controlling their sex. However, most of the genes on these chromosomes control things that have nothing to do with sex. In the rare form of hemophilia that we mentioned earlier, the reason that it occurs more frequently in males, is because the phenotype is controlled by a gene found on the X chromosome, in a section which has no partner on the Y chromosome. If a female has a bad copy of the gene, and her male child inherits this copy, he will have the disorder, he has no backup copy of the X chromosome. Since one copy of the gene is sufficient for a person to clot normally, a female must inherit two bad alleles of the gene, one from each parent, in order to exhibit the disease. Which, in this case, is not possible, because the father is unaffected. As a result, this type of hemophilia affects more males than females.
In this lab, we'll look at inheritance in Drosophila. Eye color in flies is controlled by a series of genes, some controlling what kinds of pigments are made, and one particularly important gene, called the ABC transporter, which controls transports of pigments into granules in the eye. If that gene is broken, even if the fly is making pigment, that pigment will be invisible, and the fly will have white eyes. The lab exercise is to recreate one of Thomas Hunt Morgan's most famous experiments, and explore the genetic inheritance pattern of the gene encoding the pigment transporter. Is it inherited like the purple color of Mendel's pea flowers, or is it sex-linked, like hemophilia?
