Biology 321. Ì The inheritance patterns discovered by Mendel are true for genes that are located on autosomes. Ì What is an autosome?

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1 Biology 321 Ì The inheritance patterns discovered by Mendel are true for genes that are located on autosomes Ì What is an autosome? 1

2 The fly room at Columbia University ~ 1920 l to r: Calvin Bridges, A. sturtevant, Thomas Hunt Morgan Early 20 th century fly guys Ì What do the inheritance patterns of sex-linked traits look like? Ì First look at experiments done in the early 1900 s by a fruitfly geneticist named Thomas Hunt Morgan 2

3 Ì The fruit fly Drosophila melanogaster has been used extensively in genetic research because it is a good experimental organism: small size (2mm) 12 day generation time large broods of progeny external anatomy provides for all sorts of possibilities for interesting phenotypic variation The complete DNA sequence of the fly genome was completed in

4 Ì Morgan was doing a routine transfer of his wildtype stocks when he noted a white-eyed male fly in among a stock of wild-type red-eyed animals What do we mean by wild-type phenotype? 4

5 Wild-type phenotype: the phenotype observed in the standard lab stock or seen most commonly in the wild population In Drosophila, red eye color is the wild-type phenotype 5

6 Morgan retrieved this white-eyed fly and did a series of crosses: Male fruitflies have a stereotyped courtship display involving following and wing-extension and vibration: see link below form or info 6

7 MEANWHILE back to MORGAN S experiments [we will work through the crosses on the board] Ì These results differed from typical Mendelian results in two ways: 1. The results of reciprocal crosses were different 2. F2 progeny ratios not in quarters Ì Remember that when Mendel performed reciprocal crosses between his various plant lines, he always go the same result: when he crossed yellow with green he always got yellow F1 regardless of whether the pollen came from the green-seeded plant or the yellow-seeded plant Ì This will almost always be true if the gene for the trait is located on an autosome Ì Morgan interpreted the results of these crosses using information that he had about the chromosome constitution of Drosophila Ì Morgan knew that Drosophila females had 4 regular chromosome pairs but that Drosophila males had 3 regular chromosome pairs plus a heteromorphic pair 7

8 What does heteromorphic mean? prophase of meiosis I in the testis of a salamander 8

9 Ì Heteromorphic means literally different form: a heteromorphic chromosome pair is a chromosome pair in which there is some difference in size or shape between the two chromosomes that synapse during prophase of the first meiotic division 9

10 Ì A Drosophila male has an X and a Y chromosome Ì These X and Y chromosomes synapse and segregate during meiosis I like autosomal homologues would. Ì To explain his data, Morgan proposed that a gene for eye color in Drosophila was present on the X chromosome with no counterpart on the Y chromosome Ì Thus females would have two copies of the gene and males would have one copy 10

11 Ì Assigning allele symbols Ì Mendel s style of allele notation would use the letter R (dominant phenotype is red eyes) as the gene designation with R= red (dominant) allele r= white recessive allele Ì Drosophila geneticists assign a name and letter symbol to the gene based on the mutant phenotype. So the gene that differs in the white and red-eyed flies is designated the white (w) gene In Drosophila, wild-type allele is often indicated as a + superscripted. w + = wildtype (red) allele w = mutant (white) allele Ì Fill in the genotypes of the reciprocal crosses: use X w+ for red, wild-type allele and X w for white allele. Ì The results of the reciprocal crosses are consistent with the eye color gene being on the X chromosome with no counterpart on the Y chromosome 11

12 Conventions that you must adhere to with respect to designating allele symbols: if you are using upper and lower case letters, the upper case always symbolizes the dominant allele a (+) superscript, always symbolizes the wild-type allele -- assuming that you have a reference point that indicates what phenotype is wildtype and what is mutant a wild-type allele is often, BUT NOT always dominant Ú make no a priori assumptions regarding the dominance of a wild-type allele 12

13 The Gene Name Game Nature 411: The complex, confusing, sometimes amusing and often intimidating world of gene names 13

14 The naming of genes: Drosophila style 14

15 question 1 pop culture quiz : Like many Drosophila genes, the tinman gene is named for its mutant phenotype. What structure is missing in a fly with a mutated tinman gene? 15

16 lots of genes are named for their loss-of-function phenotypes [OK, we re all adults here] question 2: what structure(s) are missing in flies mutated in the ken and barbie gene? 16

17 Don t believe there is a gene with this name? Check it out at the Interactive Fly: Zebrafish geneticists are not immune to this gene naming weaknesses: nicotine response genes (hbog and bdav) named for these two people: 17

18 Gene names: clever, obscure and often downright bad 18

19 19

20 Nettie Stevens was a talented cytogeneticist who discovered heteromorphic chromosome pair in insects. She was the first to propose that the X and Y -bearing sperm determined the sex of the zygote. 20

21 The Drosophila heteromorphic pair consists of the X and the Y chromosome: They synapse and segregate during meiosis like autosomal homologs Ì Implicit in our analysis of Morgan s crosses is the idea that sex chromosomes segregate into different gametes as paired homologs would Ì But Morgan suggested that these chromosomes do not carry the same genes -- so why or how do they pair in meiosis? 21

22 Sex chromosomes can be divided into two regions Pairing: region of genetic homology where pairing occurs during meiosis Differential region: non-homologous region à genes in this region have no counterpoint on the other sex chromosome 22

23 Hemizygous: genes located in the differential region of the X chromosome are hemizygous in males because males only have one copy of the gene Human X (left) and Y chromosomes Nature 423: 810 June 19, 2003 Tales of the Y chromosome 23

24 Gene and DiseaseMapView of autosomes, X & Y chromosomes 24

25 View of Homo sapiens genome Gene and DiseaseMapView of autosomes, X & Y chromosomes 25

26 Chromosomal Sex-determining Mechanisms Organism* Female Male Comments Mammals Some amphibians and reptiles Many insects such as the fruitfly Drosophila Some plants with male and female sexes XX XY Males produce two different types of sperm: 50% carry an X chromosome and 50% a Y chromosome Cannabis sativa: XX females and XY male plants * While the taxa listed have XX & XY chromosomes, the primary sex-determining signal varies. For example in humans, sex is determined by the presence or absence of the Y-linked SRY gene. But, in Drosophila, sex is determined by the number of X chromosomes. 26

27 Organism female male Comments Some insects (including spiders) Some roundworms -such as Caenor habditis elegans XX XO Y chromosome is absent. Males have a single X chromosome and produce two different types of sperm: 50% bearing an X chromosome and 50% with no sex chromosome Pattern of sex linkage same as XX, XY species 27

28 Organism Birds Some insects such as moths and butterflies Some amphibians and reptiles such as KOMODO dragons female male Comments ZW ZZ By convention, Z and W are used to indicate the sex chromosomes in these species. The Z chromosome is equivalent to the X chromosome. Females produce two different types of eggs: 50% carry the Z chromosome and 50% carry the W chromosome. 28

29 Organism female male Comments Bee, wasps and ants (Hymenoptera) diploid haploid Males usually develop from unfertilized eggs; females from fertilized eggs. There are no sex chromosomes per se 29

30 Why are there so many different mechanisms of genetic sex determination? What do you know about non-genetic sex-determining mechanisms? 30

31 In many lineages, the primarily Sex Determining signal evolved from an ancestral environmental signal (probably TSD) into a diverse array of genetic mechanisms as illustrated in the previous slides Current Biology 16, R736 R743, September 5,

32 Where did the X and Y come from? Clues from the present-day mammalian Y Genes in the NRY, or nonrecombining region of the Y (blue in diagram), have helped reveal the evolutionary history of the X and the Y. The region is so named because it cannot recombine, or exchange DNA, with the X. Only genes that still work are listed. About half have counterparts on the X (red); some of these are housekeeping genes, needed for the survival of most cells. Certain NRY genes act only in the testes (purple), where they likely participate in male fertility. 32

33 Y is the Y a shadow of its former self? About 300 million years ago the mammalian X and Y chromosome probably looked a lot like a regular pair of homologous autosomes* (300 million years = paleozoic/mesozoic/cenozoic?) before/during/after dinosaurs?) The functionally specialized Y chromosome highlights two evolutionary processes that are thought to have produced the mammalian chromosome: genetic decay accumulation of genes that specifically benefit male fitness * the Z & W sex chromosomes evolved independently from a different set of autosomes 33

34 Sex chromosomes (in birds and mammals) are thought to have evolved independently from what were 300 million years ago a regular pair of chromosomes 34

35 The loss of genes in the Y chromosome probably resulted from a series of events which included: Evolution of the male-determining SRY gene from a gene (called SOX) found on both ancestral chromosomes (the X chromsome still carries a copy of this gene) Chromosomal rearrangements occur between the ancestral chromosomes: progressive loss of recombination between increasingly larger segments of the ancestral X and Y chromosomes [due to structural rearrangements of the Y chromosome that inhibited pairing and crossing-over with the X] Ancestral Y starts to accumulate mutations: loss of recombination meant that on the evolving Y chromosome mutations accumulated in genes-- these mutations couldn t be purged by recombination with a homolog (see diagram below) Over millions of years, the number of functional genes on the Y chromosome declines dramatically Due to this genetic decay the non-recombining region of the human Y chromosome has retained only about 3% (19/ 664) of its ancestral autosomal genes 35

36 Huh? Genetic Decay? BUT why didn t the X chromosome decay? 36

37 Mutations on the evolving X chromosome could be purged by recombination that occurred during meisois in female animal + = wildtype allele a, b = deleterious mutation 37

38 Gene Score Card Sort the Y linked genes into three categories: 1. Genes in the pairing region (synapsis and crossing-over during prophase of meiosis I occurs here): about two dozen (29 to be exact) ancestral genes are found on both the X and Y chromosome in this region 2. Residual ancestral genes in the non-recombining region (are also on the X chromosome): 19 genes 3. Genes required for male sex-determination (Sry) and male fitness (not represented on the X chromosome): at least several genes male fertility genes include those required for normal spermatogenesis (infertile men have deletions of specific regions) NATURE VOL MARCH

39 Speculative map of the Y chromosome showing genes related to male fitness that have may accumulated on the Y chromosome From less politically correct days: Science 261: 679 August 6,

40 Y-linked genes in other species Male (top) guppy with colorful ornamentation thought to enhances sexual attraction but tradeoff is increased visibility to predators Female (bottom) does not exhibit bright colors -- apparently for female, the colors do not enhance attractiveness to potential mates enough to overcome increasing visibility to predators This trait is know to be Y-linked 40