Biology 321 The inheritance patterns discovered by Mendel are true for genes that are located on autosomes What is an autosome? 1
The fly room at Columbia University ~ 1920 l to r: Calvin Bridges, A. sturtevant, Thomas Hunt Morgan Early 20 th century fly guys What do the inheritance patterns of sex-linked traits look like? First look at experiments done in the early 1900 s by a fruifly geneticist named Thomas Hunt Morgan 2
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 2000 3
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
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
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 http://fire.biol.wwu.edu/trent/trent/fruitflymating.jpg 6
It s not just about white vs red eyes or curled vs straight wings There are many mutant strains of Drosophila where the male courtship display is abnormal. The fruitless mutation (next page) causes males to court other males as well as females. 7
. Genetics. 1989 April; 121(4): 773 785. See also: http://fire.biol.wwu.edu/trent/trent/nytgayfruitflies.pdf 8
Jargon check Statement: Fruitless homozygotes court both male and female fruitflies What we really mean: Male fruitflies that are homozygous for a loss-of-function mutation in the fruitless gene court both male and female fruitflies. Wild-type males court females only. 9
Using models to explore the genetic control of behavior A male Drosophila fruitfly performs a wing threat, typical aggression behaviour, towards a rival male. Liming Wang and David Anderson show that the volatile pheromone cva promotes male-to-male aggression by activating olfactory sensory neurons expressing the receptor protein, Or67d. This work opens the study of aggressive behaviour to detailed genetic manipulation and investigation. Cover image: Liming Wang & Michael Maire, Caltech. 10
One way a male Drosophila shows aggression is by "lunging," in which it rears up on its hind legs and snaps down with its forelegs on its opponent. (Credit: Caltech/Liming Wang and Michael Maire) Want to know more about genes and behavior? Check out this link: http://www.nature.com/scitable/topicpage/behavioral-genomics-29093 11
MEANWHILE back to MORGAN S experiments [we will work through the crosses on the board] 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 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 This will almost always be true if the gene for the trait is located on an autosome Morgan interpreted the results of these crosses using information that he had about the chromosome constitution of Drosophila Morgan knew that Drosophila females had 4 regular chromosome pairs but that Drosophila males had 3 regular chromosome pairs plus a heteromorphic pair What does heteromorphic mean? 12
prophase of meiosis I in the testis of a salamander 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 pair 13
A Drosophila male has an X and a Y chromosome These X and Y chromosomes synapse and segregate during meiosis I like autosomal homologues would. 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 Thus females would have two copies of the gene and males would have one copy 14
Assigning allele symbols 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 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 Fill in the genotypes of the reciprocal crosses: use X w+ for red, wild-type allele and X w for white allele. 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 15
The naming of genes: Drosophila style http://tinman.vetmed.helsinki.fi/eng/drosophila.html 16
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? 17
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? 18
Don t believe there is a gene with this name? Check it out at the InteractiveFly: http://www.sdbonline.org/fly/genebrief/ken&barbie.htm 19
Gene names: clever, obscure and often downright bad 20
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 make no a priori assumptions regarding the dominance of a wild-type allele 21
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. 22
The Drosophila heteromorphic pair consists of the X and the Y chromosome: They synapse and segregate during meiosis like autosomal homologs Implicit in our analysis of Morgan s crosses is the idea that sex chromosomes segregate into different gametes as paired homologs would But Morgan suggested that these chromosomes do not carry the same genes -- so why or how do they pair in meiosis? 23
Sex chromosomes can be divided into two regions Pairing: region of genetic homology where pairing occurs during meiosis Differential region: non-homologous region genes in this region have no counterpoint on the other sex chromosome 24
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 25
Gene and DiseaseMapView of autosomes, X & Y chromosomes http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gnd&part=a272 26
View of Homo sapiens genome http://www.ncbi.nlm.nih.gov/projects/mapview/map_search.cgi?taxid=9606 Gene and DiseaseMapView of autosomes, X & Y chromosomes http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gnd&part=a272 27
Chromosomal Sex-determining Mechanisms Shaded cells = diploid animals 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 28
Organism female male Comments Some insects (including spiders) Some roundworms (such as Caenorhabditis 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 29
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. 30
Organism female male Comments Bee, wasps and ants diploid haploid Males usually develop from unfertilized eggs; females from fertilized eggs. There are no sex chromosomes per se 31
What about non-chromosomal sex-determining mechanisms? 32
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. 33
The X & Y chromosomes originated a few hundred million years ago from the same ancestral autosome. Y then is the Y a shadow of its former self? 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 Huh? Genetic Decay? About 300 million years ago the mammalian X and Y chromosome probably looked a lot like a pair of homologous autosomes* (300 million years = paleozoic/mesozoic/cenozoic?) before/during/after dinosaurs?) * the Z & W sex chromosomes evolved independently from a different set of autosomes 34
The dis d (disrespected) Y chromosome: quote from Nature August 14, 2003.Until recently, the Y chromosome seemed to fulfil the role of juvenile delinquent among human chromosomes -- rich in junk, poor in useful attributes, reluctant to socialize with its neighbors and with an inescapable tendency to degenerate.. HUH what does this mean? This question is serious. Want to know more? Check out this Scientific American article: Why is the Y so weird? http://fire.biol.wwu.edu/trent/trent/whyyweird.pdf 35
Sex chromosomes (in birds and mammals) are thought to have evolved from what were 300 million years ago a regular pair of chromosomes ome probably resulted from series of events which included: Th e los s of ge ne s in th e Y ch ro m os a 36
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 chromosomal inversions that inhibited crossing-over] 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 BUT why didn t the X chromosome decay? 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 38
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Speculative map of the Y chromosome Science 261: 679 from less politically correct days: August 6, 1993 42