Genetics-5

Chromosomes are still

attached by chiasmata and cohesin.

Males, in contrast, have only

a single X chromosome (from the female parent), and thus only a single allele for each of these genes.

Instead, a comparison of the two experiments with these particular

X chromosome genes demonstrates that the observed frequencies of the various types of progeny depend on how the arrangement of alleles in the F1 females originated

All the F1 progeny are

double heterozygotes (b c+ / b+ c) and are phenotypically wild type

The phenotypes of the offspring thus indicate the kinds of ________________ + example

gametes received from the mother. - For example, a black fly with normal wings would be genotype b c+ / b c; because we know it received the b c combination from its father, it must have received b c+ from its mother

Syntenic genes -

genes located on the same chromosome

The hallmark of linkage is that a dihybrid produces

more parental gametes than recombinant gametes; as a result, the progeny ratio in a dihybrid cross involving linked genes is not 9:3:3:1

The relative numbers of the four X-linked gene combinations passed on by the dihybrid F1 females' gametes reflect

significant departure from the 1:1:1:1 ratio expected of independent assortment

You should also pay attention to

slash symbol (/), which is used to separate genes found on the two chromosomes of a pair (either the X and Y chromosomes as in this case, or a pair of X chromosomes or homologous autosomes).

Had Mendel's two genes been linked, the phenotypic ratio in the F2 would no longer have been 9:3:3:1 because

the parental gametes would have been present at greater frequency than the recombinant gametes

Conversely, if the alleles of the parents are configured differently (A b / A b × a B / a B) and the F1 are therefore A b / a B, then

two 3/16 genotypic classes would increase at the expense of the 9/16 and 1/16 classes (not shown).

As we outline various crosses, remember that females carry

two X chromosomes, and thus two alleles for each X-linked gene

This preponderance of parental combinations among the F2 genotypes reveals that

two genes are linked: The parental combinations of alleles travel together more often than not.

Figure 5.5 depicts a cross between

two pure-breeding strains: black-bodied females with straight wings (b c+ / b c+) and brown-bodied males with curved wings (b+ c / b+ c)

The remaining half of the gametes will be of

two recombinant types, in which reshuffling has produced either w+y+ or w y allele combinations not seen in the P generation parents of the F1 females

Figure 5.5 Autosomal genes can also exhibit linkage

- A testcross shows that the recombination frequency for the body color (b) and wing shape (c) pair of Drosophila genes is 23%. - Because parentals outnumber recombinants, the b and c genes are genetically linked and must be on the same autosome

Detecting linkage by analyzing the progeny of dihybrid crosses: X-linked genes #2

- Compare allele configurations in F2 to P generation - Deviation from 1:1:1:1 segregation in F2 indicates the genes are linked - Note that in this cross involving X-linked genes, only the F2 male progeny were counted

Note that in this cross:

- F1 males get their only X chromosome from their mothers - F1 females are dihybrids

We can explain why the two genes fail to assort independently in one of two ways. [3]

- The w y+ and w+ y combinations could be preferred because some intrinsic chemical affinity exists between these particular alleles. - Alternatively, these combinations of alleles might show up most often because they are parental types. - That is, the F1 female inherited w and y + together from her P generation mother, and w+ and y together from her P generation father; the F1 female is then more likely to pass on these parental combinations of alleles, rather than the recombinant combinations, to her own progeny.

Recombination frequencies between two genes never exceed

50%

Of the F2 males,

67.2% are parental types (w+ m+ and w m), while the remaining 32.8% are recombinants (w m+ and w+ m).

Linked autosomal genes are not inherited according to

9:3:3:1 Mendelian ratio expected for two independently assorting, noninteracting genes, each with one completely dominant and one recessive allele

Linkage thus undoes the basis of

9:3:3:1 ratio

Figure 5.2 When genes are linked, parental combinations outnumber recombinant types

Doubly heterozygous w y+/ w+ y F1 females produce four types of male offspring. Sons that look like the father (w+ y / Y) or mother (w y+/ Y) of the F1 females are parental types. Other sons (w+y+/ Y or w y / Y) are recombinant types. For these closely-linked genes, many more parental types are produced than recombinant types.

Figure 5.3 Designations of parental and recombinant relate to past history

Figure 5.2 has been redrawn here as Cross Series A for easier comparison with Cross Series B, in which the dihybrid F1 females received different allelic combinations of the white and yellow genes. Note that the parental and recombinant classes in the two cross series are the opposite of each other. The percentages of recombinant and parental types are nonetheless similar in both experiments, showing that the frequency of recombination is independent of the arrangement of alleles.

Figure 5.4 The 9:3:3:1 ratio is altered when genes A and B are linked.

For linked genes, the F2 genotypic classes produced most often by parental gametes increase in frequency at the expense of the other classes. In the A B/a b dihybrid cross shown here, the A- B- and aa bb classes in the F2 will occur at higher frequencies, and the two other classes (A- bb and aa B-) at lower frequencies than predicted by the 9:3:3:1 ratios. Note that the blue colors and the relative sizes of the boxes in the Punnett square denote the frequencies at which particular genotypic classes will appear in the F2 generation

Detect linkage by generating

a double heterozygote and crossing to homozygous recessive (testcross)

We look first at two X-linked genes that determine

a fruit fly's eye color and body color. These two genes are said to be syntenic because they are located on the same chromosome.

Parental gametes contain __________________, recombinant gametes contain _______________________

alleles inherited together from a single grandparent; recombinant gametes contain alleles inherited from different grandparents

To avoid confusion, note that lowercase y and y+ refer to

alleles of the yellow gene, while capital Y refers to the Y chromosome (which does not carry genes for either eye or body color)

The expected 9:3:3:1 ratio of genotypes is

altered when genes are linked

A cross of red-eyed females with normal wings (w+ m+ / w+ m+) and white-eyed males with miniature wings (w m / Y) yields

an F1 generation containing all red-eyed, normal-winged flies

The genes for eye and body color that reside on the X chromosome in Drosophila are

an extreme illustration of the linkage concept.

Genes on the same chromosome that do not

assort independently are said to be linked.

Genes linked together on the same chromosome usually

assort together

Autosomal linkage

b - black body c -- curved wing

Fruit flies, for example, carry an autosomal gene for

body color (in addition to the X-linked y gene); the wild type is once again brown, but a recessive mutation in this gene gives rise to black (b)

Frans Janssens - 1909, observed

chiasmata at chromosomes during prophase of meiosis I

T. H. Morgan - suggested

chiasmata were sites of chromosome breakage and exchange

We can see whether the 1:1:1:1 ratio of the four kinds of gametes actually materializes by

counting the different types of male progeny in the F2 generation, as these sons receive their only X-linked genes from their maternal gamete.

Early twentieth-century geneticists found it difficult to interpret

crosses involving autosomal genes such as that shown in Fig. 5.4 because it was hard to trace which alleles came from which parent

Recombination: A result of

crossing-over during meiosis

A second set of crosses involving the same genes but with a different arrangement of alleles explains why

dihybrid F1 females do not produce a 1:1:1:1 ratio of the four possible types of gametes

If these two Drosophila genes for eye and body color assort independently, as predicted by Mendel's second law,

dihybrid F1 females should make four kinds of gametes, with four different combinations of genes on the X chromosome—w y+, w+ y, w+ y+, and w y

H. Creighton and B. McClintock (corn) and C. Stern (Drosophila) - 1931,

direct evidence that genetic recombination depends on reciprocal exchanged of chromosomes

In a cross between a female with mutant white eyes and a wild-type brown body (w y+/w y+) and a male with wildtype red eyes and a mutant yellow body (w+ y / Y), the F1 offspring are

divided evenly between brown-bodied females with normal red eyes (w y+/w+ y) and brown-bodied males with mutant white eyes (w y+/Y)

The white gene was introduced in Chapter 4; you will recall that

dominant wild-type allele w+ specifies red eyes, while the recessive mutant allele w confers white eyes.

Equal numbers of each of the four gamete types— independent assortment—means that

each one of the 16 boxes in the Punnett square for the F2 is an equally likely fertilization with a frequency of 1/16

With two alleles for each X-linked gene, one derived from

each parent, the dominance relations of each pair of alleles determine the female phenotype.

Testcrosses clarify linkage because

each phenotypic class of progeny corresponds to each gamete type produced by the dihybrid parent.

These four types of gametes should occur with

equal frequency, that is, in a ratio of 1:1:1:1. - If it happens this way, approximately half of the gametes will be of the two parental types, carrying either the w y+ allele combination seen in the original female of the P generation or the w+y allele combination seen in the original male of the P generation.

The RF of linked genes cannot __________ + [2]

exceed 50% • Meioses without crossovers produce only parental chromosomes. • Single and double crossovers produce a 1:1 parental to recombinant chromosome ratio on average

In Drosophila, a mutation for miniature wings (m) is also

found on the X chromosome

Mendel observed the 9:3:3:1 phenotypic ratio in the F2 of his dihybrid crosses because

four possible gamete types (A B, A b, A B, and a b) were produced at equal frequency by both parents.

Recombination frequencies are the basis of

genetic maps

Figure 5.4 shows the consequences of linkage if the F1 dihybrid individuals were both of

genotype A B / a b : The 9/16 and 1/16 classes of F2 would have increased at the expense of the two 3/16 classes.

Thus w y / Y represents

genotype of a male with an X chromosome bearing w and y, as well as a Y chromosome; phenotypically this male has white eyes and a yellow body.

Synaptonemal complexes help

homologous chromosomes pair, but they disappear during prophase I.

If people have roughly 27,000 genes but only 23 pairs of chromosomes, most human chromosomes must carry

hundreds, if not thousands, of genes.

Physical markers were used to

identify specific chromosomes

Designation of "parental" and "recombinant" relate to

past history

The RF of unlinked genes is 50% due to

independent assortment

The reshuffled recombinant classes occur

less often

Autosomal genes can also exhibit

linkage

By comparison, two genes are considered

linked when the number of F2 progeny with parental genotypes exceeds the number of F2 progeny with recombinant genotypes

If recombination did not occur

nondisjunction during meiosis I would happen frequently

However, by setting up testcrosses in which

one parent was homozygous for the recessive alleles of both genes, as detailed in the next section, geneticists can easily analyze the gene combinations received in the gametes from the other, doubly heterozygous parent

Note that the parental configurations in these two crosses are

opposite of each other

When genes assort independently, the numbers of

parental and recombinant F2 progeny are equal because a doubly heterozygous F1 individual produces an equal number of all four types of gametes.

It is important to appreciate that the designation of

parental and recombinant gametes or progeny of a doubly heterozygous F1 female is operational, that is, determined by the particular set of alleles she receives from each of her parents

Note that in both experiments, it is

parental classes—the combinations originally present in the P generation—that show up most frequently in the F2 generation

The two genes are so tightly coupled that

parental combinations of alleles— w y+ and w+ y (in Cross Series A of Fig. 5.3) or w+ y+ and w y (in Cross Series B)—are reshuffled to form recombinants in only 1 out of every 100 gametes formed

By far, the largest numbers of gametes carry

parental combinations w y+ and w+y.

Recombinant gametes are less frequent than

parental gametes when genes are linked

As Fig. 5.5 shows, roughly 77% of the testcross progeny in one experiment received

parental gene combinations (that is, allelic combinations transmitted to the F1 females by the gametes of each of her parents), while the remaining 23% were recombinants.

Genetic markers were used as

points of reference for recombination

Unequal numbers of the four gamete types are

produced, so each box of the Punnett square in Fig. 5.4 no longer represents an equally likely fertilization

Detecting linkage by analyzing

progeny of dihybrid crosses: X-linked genes #1

Recombination helps ensure

proper chromosome segregation during meiosis I

The same is not true for the F1 females, who

received w and y + on the X from their mother and w+ y on the X from their father. - These F1 females are thus dihybrids.

In a testcross of the F1 females with b c / b c males, all the offspring receive

recessive b and c alleles from their father.

Evidence that recombination results from

reciprocal exchanges between homologous chromosomes

Because the parental classes outnumbered

recombinant classes, we can conclude that the autosomal genes for black body and curved wings are linked

Linked genes may become separated by

recombination

A. H. Sturtevant - proposed that

recombination frequencies (RF) could be used as a measure of physical distance between two linked genes

In this second set of crosses, the original parental generation consists of

red-eyed, brown-bodied females (w+ y+ / w+ y+) and white-eyed, yellow-bodied males (w y / Y), and the resultant F1 females are all w+ y+ / w y dihybrids

The parental combinations for color and wing size are

reshuffled in roughly 33 (instead of 1) out of every 100 gametes.

A second gene on the same autosome helps determine

shape of a fruit fly's wing, with the wild type having straight edges and a recessive mutation (c) producing curves.

This time, as Cross Series B in Fig. 5.3 shows, w+ y / Y and w y+ / Y are

the recombinants that account for little more than 1% of the total, while w y / Y and w+ y+ / Y are the parental combinations, which again add up to almost 99%.

Note that the male progeny look like

their mother because their phenotype directly reflects the genotype of the single X chromosome they received from her.

. Instead of assorting independently, the genes behave as if

they are connected to each other much of the time

In other words, the two parental allele combinations of these

tightly linked genes are inherited together 99 times out of 100

It is easy to understand how genes that are physically connected on the same chromosome can be transmitted

together and thus show genetic linkage.

But compared to the 99% linkage between the w and y genes for eye color and body color, the linkage of

w to m is not that tight.

You can see that no preferred association of

w+ and y or of y+ and w exists in this cross.

The genotype of the dihybrid F1 females is

w+ m+ / w m

The alleles of the yellow body color gene are

y+ (the dominant wild-type allele for brown bodies) and y (the recessive mutant allele for yellow bodies).

Two X-linked genes in Drosophila with recessive alleles

• w+ (red eyes) and w (white eyes) • y + (brown body) and y (yellow body)