Alleles and Inheritance

Genetic information for human is stored in 23 chromosomes, which come in pairs - one from the mother, the other from the father. Thus every individual has two copies of each gene. Alleles are different forms of a gene located in exactly the same position on homologous chromosomes as shown in the left of Figure 01. The sequence of the DNA base pairs for the brown eye and blue eye alleles (the bey2 gene) as shown in the right of Figure 01 is essentially similar except the one base pair A-T in the former is replaced by G-C in the latter. Homozygous refers to the case where the two alleles are identical; while heterozygous signifies the alleles have different forms. The allele expressed in the heterozygote is dominant; while the one not expressed is recessive. In the bey2 example, brown is dominant over blue unless it is damaged. In that case, the recessive allele takes over as the functional gene.

Figure 01 Allele [view large image]

Genotype is the genetic make-up of an allele. The allele responsible for a trait is usually indicated by a capital letter for the dominant factor (such as B for brown eye) and by a lowercase letter for the recessive factor (such as b for blue eye). Phenotype refers to the physical characteristics (such as brown eye or blue eye). The transmission of traits is usually plotted on the Punnett square. The following examples trace the eye colour transmission to progeny from different combination of male/female genotypes.

The above example for eye colour genotype is over simplified. Actually, at least three genes are involved in eye colour determination.

		The distinction between dominant and recessive alleles as proposed by the Augustinian monk Gregor Mendel in 1866 has been modified somewhat by the discovery of imprinting in the last 20 years. An imprinted gene is the silenced gene in either the male or female, and in effect the gene becomes haploid - only one allele works (see Figure 02). Thus, the advantage of having a backup copy is lost. As a result of this unique genetic make-up, imprinted genes act as nodes of susceptibility for all kinds of diseases such as asthma, cancer, diabetes, obesity and many behavioral and developmental disorders - a list that is surprisingly long given the limited number of imprinted genes identified so far. The imprint is reset in each new generation as shown in Figure 03 such that the maternal and paternal imprints would reestablished according to the offspring's own sex.
Figure 02 Imprint [view large image]	Figure 03 Imprint Reset

	Genetic imprinting seems to coevolve with the practice of live birth in primitive mammals about 180 million years ago. Egg-laying monotremes such as the platypus are the most ancient group of mammals and do not have imprinted genes. The first example of imprinting appeared in a common, now-extinct ancestor of marsupials and eutherian, or placental, mammals (Figure 04).
Figure 04 Evolution of Imprint [view large image]

Despite the genetic vulnerability that imprinting dictates, every placental mammal studied so far has retained this attribute in its genome. Clearly there must be some advantage that offsets the risk, although exactly what this benefit might be has generated much debate. One theory argues that imprinting is a mechanism to prevent unfertilized eggs developing into new individual (virgin birth). A second hypothesis is that the imprinting gene is disabled because it is too close to a

Figure 05 Theory of Imprinting
[view large image]

parasite DNA sequence. Yet another conjecture suggests that imprinting protects females against germ-cell tumors by guarding against excess placental growth.

However, most scientists do not think imprinting is a beneficial adaptation. The most widely accepted theory of its origin is the conflict hypothesis. It suggests that imprinting arose because of a genomic tug-of-war between mothers and fathers over the use of maternal resources by the fetus. In mammals that bear live offspring, the male's evolutionary fitness is maximized if his offspring monopolizes the female's energy reserves during gestation. The female's best strategy demands that she not invest all of her resources in a single offspring (see Figure 05). It is important to note that these theories are about the evolutionary logic of imprinting rather than the molecular mechanisms, which is still unknown.