Thomas Cline practicing developmental geneticist (Drosophila melanogaster) former Berkeley undergrad (‘64-68) Office hours: Monday 5-6pm (door closes @ 5:15p) Friday 4-5 pm 11 Koshland Hall

Topics for today: recombination (genetic maps) complementation (bacterio)phage as an experimental system famous geneticists Reading for today and Monday: Chapter 7 (and skim Chapter 8) Problems: Chp 7, 16-24

genetics: epigenetics: From your textbook’s glossary: the science of heredity epigenetics: study of states of gene functionality that are not encoded within the DNA sequence but that are still heritable from one generation to the next.

X genetics: genes epigenetics: study of states of gene functionality From your textbook’s glossary: genetics: X the science of heredity genes epigenetics: study of states of gene functionality that are not encoded within the DNA sequence but that are still heritable from one generation to the next.

From your textbook’s glossary: genetics: the science of genes gene: basic unit of biological information; specific segment of DNA in a discrete region of a chromosome that serves as a unit of function by encoding a particular RNA or protein. (only in cis) encodes what what about aspects relevant to when? where? how much?

What do we do with the Drosophila Dscam gene? basic unit of biological information; specific segment of DNA in a discrete region of a chromosome that serves as a unit of function by encoding a particular RNA or protein. (only in cis) What do we do with the Drosophila Dscam gene? (Down syndrome cell adhesion molecule) …encodes 38,000 different proteins (via alternative pre-mRNA splicing) (Drosophila has “only” 14,000 genes)

a difference that makes a difference w/ respect to biological function gene: basic unit of biological information; specific segment of DNA in a discrete region of a chromosome that serves as a unit of function by encoding a particular RNA or protein. (only in cis) information: a difference that makes a difference w/ respect to biological function “nonsense” DNA sequence (encodes nothing… …such as DNA between genes?) gene DNA sequence (encodes particular RNA or protein) VS.

“nonsense” DNA sequence gene DNA sequence VS. (encodes nothing… …such as DNA between genes?) gene DNA sequence (encodes particular RNA or protein) VS. This is NOT the difference that really concerns geneticists. (although we will touch on it today) genetic map

alleles: The difference that really concerns geneticists. alternative forms of a single gene DIFFERENT forms of a single gene If you understand the concept of allelism, you will understand what genetics is all about and what geneticists mean by genes

(with respect to seed color) Mendel defined alleles (but it is not a particularly useful definition): given: Heritable character difference (e.g. seed color) IF: pure-breeding yellow pure-breeding green X hybrid (yellow) hybrid (yellow) X (1:2:1) (genotype) pure-breeding pure-breeding yellow pure-breeding green hybrid yellow yellow (phenotype) AND NOTHING ELSE (with respect to seed color) This particular seed color difference is due to a difference in (the alleles of) a single gene Then: Y & y are alleles; hybrid yellow is Y/y

(with respect to seed color) pure-breeding yellow pure-breeding green X hybrid (yellow) hybrid (yellow) X (1:2:1) pure-breeding yellow pure-breeding green hybrid yellow AND NOTHING ELSE (with respect to seed color)

…and by extension the allele responsible for the difference between the recessive and dominant characters

(with respect to seed color) hybrid (yellow) X pure-breeding yellow pure-breeding green hybrid yellow AND NOTHING ELSE (with respect to seed color) (1:2:1) Y vs. y are alleles as defined by a segregation test (1) unchanged in the hybrid (2) segregate during meiosis The gene defined as the unit of segregation during meiosis (…not with respect to function)

Problem: What if there are really TWO genes involved … that are very closely linked? AB/AB X ab/ab AB/ab How hard do we have to look before deciding we must be dealing with a single gene difference? self almost all: AB/AB AB/ab ab/ab but occasionally rare recombinants (“non-parentals”) such as: Ab/ab

Problem with the segregational definition of allelism (= definition of the gene as the unit of segregation) arose in the case of multiple alleles difference between pb. whiteeosin vs. white+ = one gene diff. = alleles difference between pb. white-1 vs. white+ = one gene diff. = alleles difference between pb. white-1 vs. whiteeosin = one gene diff. = alleles (all based on Mendel’s test for segregation) Hence, two different alternative mutant forms (we = orange, & w-1 = white) of one wildtype gene: white+ (= red)

What’s the problem with multiple alleles? w-1/weosin X w-1/Y very rarely: w+/Y (hardly “unchanged in the hybrid”) Isn’t this just a revertant? y- w-1 sn-/ y+ we sn+ y+ w+ sn- only from heterozygous moms 2) always associated with recombination of flanking genetic markers and a specific nonparental arrangement of those markers!

w+ w-1 we Must not be “true” alleles (true alternative forms of the same gene) but rather “pseudoalleles” genetic map: yellow w-1 we singed white-A white-B genes as “beads on a string”

Must not be “true” alleles w+ w-1 we Must not be “true” alleles but rather “pseudoalleles” Didn’t pass the smell test two genes? genetic map: yellow w-1 we singed white-A white-B genes as “beads on a string”

The first example of “pseudoallelism” was lozenge: Gene A Gene B wt lz(g) lz(BS) wt Aa Bb And many more cases followed in flies, and even more in micro-organisms where one had much greater mapping resolution power

The cis-trans (complementation) test, 1949: lozenge (M. Greene) Two different recessive mutants, both with the same phenotype (small eyes and fused facets). Are they mutations in the same gene? Make two different fly lines and compare their phenotypes. Cis: Trans: wt wt wt lz(g) lz(BS) lz(g) lz(BS) wt

If flies are normal, then mutations are in different genes. Cis: Trans: wt wt wt lz(g) lz(BS) lz(g) lz(BS) wt This is a control experiment. The flies will be wild-type regardless of whether BS and g are in the same gene or not. If flies are normal, then mutations are in different genes. If the phenotype is still mutant, then BS and g must be in the same gene!!! A test for allelism (a definition of the gene) based on the PHENOTYPE OF THE HYBRID (function, not segregation & NOT MENDEL!)

genetic map based on segregation frequencies meiotic recombination can separate the parts of a “gene” like white or lozenge How does a genetic map of regions within a gene (as defined by the complementation test) compare with that for regions between genes (as defined by the complementation test)? do true “segregational alleles” exist, and if so, how do they compare with “functional alleles”?

Who said it?

genetic map based on segregation frequencies meiotic recombination can separate the parts of a “gene” like white or lozenge How does a genetic map of regions within a gene (as defined by the complementation test) compare with that for regions between genes (as defined by the complementation test)? do true “segregational alleles” exist, and if so, how do they compare with “functional alleles”?

Fig. 7.20 p228

American Naturalist, v56 p32 (1922) … =bacteriophage