Unit 18: Inheritance — Long Questions

After establishing the law of segregation using single traits, Mendel examined two characters together: seed shape (round R, dominant; wrinkled r, recessive) and seed colour (yellow Y, dominant; green y, recessive). He established pure-breeding lines: plants with both dominant traits (RRYY, round yellow) and plants with both recessive traits (rryy, wrinkled green). He crossed these pure-breeding plants (RRYY × rryy); all F1 seeds were heterozygous dihybrids (RrYy), showing both dominant traits (round, yellow). To test the F1 genotype, he self-fertilized the F1 plants to produce F2. Instead of a simple 3:1 ratio, the F2 generation showed four phenotypes — round yellow, round green, wrinkled yellow, and wrinkled green — in a 9:3:3:1 ratio.

Interpretation In the F1 dihybrid (RrYy), gamete formation produces four combinations (RY, Ry, rY, ry) in equal numbers. When these four types of gametes combine (4 male × 4 female), 16 combinations form in F2, giving the four phenotypes in a 9:3:3:1 ratio (9 round yellow : 3 round green : 3 wrinkled yellow : 1 wrinkled green). The appearance of new combinations not seen in either parent (round green, wrinkled yellow) proved that the alleles for seed shape segregate independently of the alleles for seed colour. On this basis, Mendel proposed the law of independent assortment: each pair of alleles assorts independently of other pairs of alleles during gamete formation.

Incomplete dominance is a type of inheritance in which neither allele of a gene pair is fully dominant over the other; in a heterozygous individual, the phenotype is intermediate between the phenotypes of both parents, rather than resembling one parent completely.

Example — Japanese Four-O'clock plant Flower colour is controlled by two alleles, red (R) and white (W), with incomplete dominance. When a pure red-flowered plant (RR) is crossed with a pure white-flowered plant (WW), all the F1 offspring are heterozygous (RW) and have pink flowers — an intermediate colour, showing that neither the red nor the white allele is completely dominant. When two pink-flowered plants are crossed (RW × RW), the F2 offspring appear in a 1:2:1 ratio: 1 red (RR) : 2 pink (RW) : 1 white (WW).

Erythroblastosis foetalis is a haemolytic disease of the foetus/newborn caused by Rh incompatibility between an Rh-negative pregnant mother and an Rh-positive foetus.

Antigen-antibody mechanism It occurs when an Rh-negative mother (dd) carries an Rh-positive baby (DD or Dd, Rh-antigen present). During pregnancy or delivery, some foetal blood (carrying Rh-antigen) may enter the mother's bloodstream. Since the mother lacks the Rh-antigen, her immune system recognizes it as foreign and produces anti-Rh antibodies against it. These antibodies can cross the placenta and enter the foetal blood, where they bind to the Rh-antigen on foetal RBCs and destroy them (antigen-antibody reaction), causing haemolytic anaemia. In severe cases this can lead to miscarriage or stillbirth. If the foetus survives, the liver and spleen enlarge trying to compensate by making more RBCs, and the breakdown of RBCs produces excess bilirubin, which causes jaundice and can damage brain cells if levels are very high.

Preventive measures Since the first Rh-positive pregnancy usually sensitizes the mother (antibody levels are initially low and the first baby is often unaffected), danger arises mainly in later pregnancies. To prevent this, an Rh-negative mother at risk is given an injection of Rh-antiserum (anti-Rh antibodies) during early pregnancy and immediately after birth. This destroys any of the baby's RBCs that may have crossed into the mother's blood before they can sensitize her immune system, preventing her from forming her own anti-Rh antibodies. (Also, interestingly, if the mother is also ABO-incompatible with the foetus, her existing anti-A or anti-B antibodies may destroy foetal RBCs quickly before she can be sensitized to the Rh-antigen, offering some natural protection.)

Polygenic inheritance is a type of inheritance in which a trait is controlled by many gene pairs (not just one), and all the alleles of these genes contribute to the trait in an additive way (some alleles increase the effect, others decrease it). The combined effect of all these genes produces a single trait that shows continuous variation in a population, rather than distinct either/or categories.

Example — Wheat grain colour Wheat grain colour ranges continuously from white to dark red and is controlled by three polygenes: A, B, and C. Each gene has a dominant allele (A, B, C) that produces red pigment, and a recessive allele (a, b, c) that produces no pigment. The genotype AABBCC produces the maximum red pigment (dark red grains), while aabbcc produces no pigment (white grains). When dark red wheat (AABBCC) is crossed with white wheat (aabbcc), the F1 generation (AaBbCc) shows an intermediate red colour. When F1 plants are self-crossed to produce F2, a wide range of grain colours appears: only 1 plant out of 64 will have the darkest red grains (AABBCC) and 1 plant will have white grains (aabbcc), while the remaining 62 plants show various intermediate shades of red (moderate to very light red), producing a continuous range of colour. Environmental factors like light, water, and nutrients also influence the final grain colour.

Gene linkage counters independent assortment: The law of independent assortment states that different gene pairs segregate independently during gamete formation. However, since thousands of genes are present on a limited number of chromosomes, many genes lie close together in a line on the same chromosome. Such genes, called linked genes, tend to be inherited together as a unit rather than assorting independently, because they travel together on the same chromosome during meiosis. This is why linkage is considered a limitation/exception to the law of independent assortment — only genes on different chromosomes, or far enough apart on the same chromosome, truly assort independently.

Crossing-over modifies the progeny During meiosis-I, homologous chromosomes undergo crossing over, in which chromatids of the two homologous chromosomes line up and exchange (swap) segments of DNA through breakage and rejoining. This recombination shuffles the alleles of linked genes between the two homologous chromosomes, so that new combinations of alleles (recombinant chromatids) are produced that were not originally present on either parental chromosome. When these recombinant chromatids go into different gametes, they produce new gene combinations in the offspring, overriding the simple 'inherited together' pattern of linkage and increasing genetic variability in the progeny.

Thomas Hunt Morgan studied two traits in Drosophila: wing length (long wing L, dominant; vestigial/short wing l, recessive) and abdomen width (broad abdomen B, dominant; narrow abdomen b, recessive).

He crossed a fly with broad abdomen and long wings to a fly with narrow abdomen and vestigial wings. All F1 flies had long wings and broad abdomens (showing dominance). He then crossed two F1 flies together (F1 × F1). According to the law of independent assortment, the F2 should have shown four phenotypes in a 9:3:3:1 ratio — 9 long wing/broad abdomen, 3 long wing/narrow abdomen, 3 vestigial wing/broad abdomen, and 1 vestigial wing/narrow abdomen. But Morgan observed only the two parental-type combinations in F2: 3/4 of the flies had long wings and broad abdomen, and 1/4 had vestigial wings and narrow abdomen — no new (recombinant) combinations appeared at all.

From this result, Morgan concluded that the genes for wing length and abdomen width are located on the same chromosome (linked genes) and therefore do not assort independently; they are inherited together as parental combinations.

In Drosophila, mammals, and most other vertebrates, sex is determined by the XX-XY mechanism, based on one pair of sex chromosomes: a rod-shaped X chromosome and a hook-shaped Y chromosome. Females have two X chromosomes (XX) while males have one X and one Y chromosome (XY). Drosophila has 3 pairs of autosomes plus 1 pair of sex chromosomes; humans have 22 pairs of autosomes plus 1 pair of sex chromosomes.

In this system, females are homogametic — they produce only one type of egg, all carrying a single X chromosome. Males are heterogametic — they produce two types of sperm in equal numbers: half carry an X chromosome and half carry a Y chromosome. If an X-bearing sperm fertilizes the egg, the resulting zygote is XX, which develops female sex organs, producing a female offspring. If a Y-bearing sperm fertilizes the egg, the zygote is XY, which develops male sex organs, producing a male offspring. Since the male's sperm determines which sex chromosome is passed on, it is the father's gamete that determines the offspring's sex in this system.

XX-XO system Found in some insects (e.g., grasshopper). There is no Y chromosome at all. A karyotype of a male grasshopper would show 22 autosomes (11 pairs) plus a single, unpaired X chromosome, giving a total of 23 chromosomes (XO). The male produces two types of sperm: half carrying an X chromosome and half being 'nullo' (carrying no sex chromosome). A karyotype of a female grasshopper would show 22 autosomes plus a pair of X chromosomes, giving 24 chromosomes total (XX); all her eggs carry one X chromosome. If an X-bearing sperm fertilizes the egg, an XX female results; if a nullo sperm fertilizes the egg, an XO male results.

ZZ-ZW system Common in birds. The autosome number varies between species, but the sex chromosomes are ZW in females and ZZ in males — the reverse pattern from mammals. A karyotype of a male bird shows a matched pair of Z chromosomes (homogametic male), while a karyotype of a female bird shows one Z and one W chromosome (heterogametic female). The female produces two kinds of eggs (half Z-carrying, half W-carrying), while all sperm from the male carry a Z chromosome. An egg fertilized with a Z-carrying egg (ZZ) gives a male offspring, and fertilization involving the W-carrying egg (ZW) gives a female offspring — so in this system it is the mother's gamete (egg) that determines offspring sex, the opposite of the XX-XY system.

Karyotype evaluation In both systems, a karyotype (the complete set of chromosomes arranged by number, size, and shape) lets one identify the sex of an individual directly — by checking whether the sex-chromosome pair is XX/XO (grasshopper) or ZZ/ZW (birds), and whether it is matched (homogametic) or unmatched (heterogametic).

In 1910, Thomas Hunt Morgan observed a mutant male Drosophila with white eyes instead of the normal red. He crossed this white-eyed male with a normal red-eyed female; all F1 progeny (both males and females) had red eyes, showing red is dominant over white.

When Morgan crossed the red-eyed F1 flies with each other, the F2 generation of 4252 flies showed a ratio greater than 3:1 (red:white), but strikingly, all the white-eyed F2 flies were males — no white-eyed females appeared.

To test whether a white-eyed female could even exist, Morgan test-crossed an F1 red-eyed female with the original white-eyed male. This cross produced both white-eyed and red-eyed males and females in a 1:1:1:1 ratio, proving that white-eyed females could indeed exist. He then crossed a white-eyed female with a red-eyed male; all the female offspring had red eyes and all the male offspring had white eyes.

From these results, Morgan concluded that the gene for eye colour is located on the X chromosome, and that the Y chromosome does not carry an allele for this gene. He called such genes sex-linked genes and the traits they control sex-linked traits — this explains why the inheritance pattern of eye colour differed between males and females in his crosses.

Sex-limited traits These are traits whose genes are present in both sexes but are expressed (switched on) in only one sex, due to anatomical or hormonal differences between males and females. Examples in humans: the genes for beard growth are present in both sexes but expressed only in males; the genes for prostate cancer are expressed only in males, while the genes for ovarian cancer are expressed only in females — in both cases, the genes are present in both sexes but anatomically relevant/expressed in only one.

Sex-influenced traits These are traits in which the same gene is expressed in both sexes, but the alleles behave with different dominance relationships depending on sex, due to hormonal differences. Example in humans: baldness. The allele for baldness is dominant in men but recessive in women — so a man can become bald if he is either homozygous (BB) or heterozygous (Bb) for the baldness allele, while a woman becomes bald only if she is homozygous recessive (bb) for it, explaining why baldness is far more common in men than women even though both sexes carry the same gene.

Haemophilia is a rare disorder in which blood fails to clot properly after an injury, due to the reduction, malfunctioning, or absence of specific blood clotting factors. There are three types: Haemophilia A and B are due to abnormal clotting factors VIII and IX, respectively, and both are X-linked recessive traits, which makes them more common in males than females (since males need only one copy of the recessive allele on their single X chromosome to be affected, while females need two copies). Haemophilia C is due to abnormal clotting factor XI and is an autosomal recessive trait, so it occurs equally in both genders.

Inheritance pattern (for the X-linked types A and B): Since the disease allele is recessive and X-linked, an affected mother will pass it to all of her sons (who have only one X chromosome and so cannot be 'protected' by a second, normal allele); a carrier (heterozygous) mother has a 50% chance of passing it to each son. If the father is haemophiliac, all his daughters will become carriers (since daughters inherit his only X chromosome) but none of his sons will inherit the trait from him (since sons get his Y chromosome, not his X).

In people with normal (trichromatic) vision, the retina has three kinds of cone cells — red-sensitive, green-sensitive, and blue-sensitive — each containing a specific opsin pigment protein. The genes for red and green opsins are located on the X chromosome, while the gene for blue opsin is on autosome 7. Colour blindness results from recessive alleles of these opsin genes.

Types Dichromacy is the perception of only two primary colours, with blindness to the third whose opsin is missing — this may be red-blindness (protanopia), green-blindness (deuteranopia), or blue-blindness (tritanopia). Monochromacy (total colour blindness) is the perception of only one colour, with blindness to two others; in blue-cone monochromacy (also called red-green colour-blindness), both red and green opsins are absent; red-cone and green-cone monochromacy are very rare.

Inheritance Since the red and green opsin genes are X-linked recessive, colour blindness follows the X-linked recessive inheritance pattern described for haemophilia — it is much more common in males (who need only one recessive allele on their single X) than in females (who need two copies). There is currently no cure for colour blindness, though colour-blind glasses, special software, and colour discrimination training can help affected individuals.

Thomas Hunt Morgan studied the inheritance of wing length (long wing L, dominant; vestigial wing l, recessive) and abdomen width (broad abdomen B, dominant; narrow abdomen b, recessive) in Drosophila. He crossed a fly with broad abdomen and long wings to one with narrow abdomen and vestigial wings; the F1 generation all had long wings and broad abdomens. He then crossed F1 flies with each other (F1 × F1).

According to the law of independent assortment, this dihybrid-type cross should have produced F2 offspring in a 9:3:3:1 ratio across four phenotype classes. Instead, Morgan found only the two parental-type combinations in F2 — 3/4 long wing/broad abdomen and 1/4 vestigial wing/narrow abdomen — with no recombinant types at all. This showed that the genes for wing length and abdomen width are located on the same chromosome, i.e., they are linked genes, and therefore did not assort independently (gene linkage).

Crossing over Gene linkage explains why genes located close together on the same chromosome usually stay together. However, during meiosis-I, homologous chromosomes can undergo crossing over, in which chromatids of the two homologous chromosomes line up and physically exchange (swap) segments of DNA by breaking and rejoining. This recombination process rearranges the alleles of linked genes, producing recombinant chromatids. When such recombinant chromatids go into different gametes, new (non-parental) combinations of traits can appear in a smaller fraction of the offspring, which is how linked genes can still show some separation — this is the basis of 'incomplete linkage', as opposed to 'complete linkage' (as Morgan observed in this particular cross, where no recombinants appeared at all).