A BI311 Student Resource
8.4: MALISASY (in single-letter amino acid code)
8.9: 5’-AUU = Isoleucine at amino terminus of protein; UUA-3’ = Leucine at carboxy terminus
8.10: This encodes the alternating polypeptide Cys-Val
8.18: There are three possible reading frames, each encoding a different repeating polymer. One has a repeating Val (GUC), one has a repeating Ser (UCG), and one has a repeating Arg (CGU).
Here are a few questions from last year’s Midterm #2 to help with your studying. Answers will appear on the blog in a few days.
#7. (3 points) In domestic cats, an X-linked gene influences coat coloration. One allele results in black coloration and a second allele causes orange coloration. Female cats with both black and orange spots are heterozygous at this X-linked locus. What is the explanation for this genotype-phenotype relationship?
a) Incomplete dominance
b) Codominance
c) Epistasis
d) Dosage compensation
#13. (3 points) A genetic distance of 0.01 cM corresponds to what recombination frequency?
a) 1
b) 0.01
c) 0.001
d) 0.0001
#20. (6 points) Cyclins and cyclin-dependent kinases (CDKs) form heterodimers that function to regulate the cell cycle. Briefly describe the specific, molecular function played by cyclins in this process, as well as the specific molecular function of CDKs.
#21. (6 points) You are studying three linked genes: D, E and F. There are two alleles for each gene (D and d, E and e, F and f). E is the gene in the middle. The genetic distance between D and E is 0.5 cM. The genetic distance between E and F is 10 cM. You perform a cross between a triply heterozygous organism and a triply homozygous recessive tester and analyze 10,000 progeny. Among the progeny, only two double-recombinants were observed. What is the degree of crossover interference (i)?
Hint: i = 1 – (coefficient of coincidence)
= 1 – (obs. # double recombinants/exp. # double recombinants)
It was all about recombination! We learned about the inheritance patterns of linked genes nearby one another on a chromosome, most importantly how to quantitatively express the incidence of co-inheritance of linked markers in terms of recombination frequencies (or, genetic distance as measured in cM). In addition, we gained an understanding of how patterns of genetic distance between marker genes with clear associated phenotypes led to the creation of genetic maps: maps revealing the relative ordering of genes along chromosome physical space. These genetic maps have been enormously helpful to both scientists learning about genetic and other biological processes in their study systems, and also to plant and animal breeders interested in producing high-value crops and livestock in the world of agriculture. The three-point testcross – appearing in lecture, homeworks, and recitation – illustrates the basic logic that underlies the construction of genetic maps.
We also learned about recombination rates (not covered in the book). This is an expressed as the genetic distance (in cM) divided by the physical distance (in Mb). Looking at recombination this way, it becomes very apparent that different regions of DNA can vary extensively in term of how ‘recombinogenic’ they are. A human chromosome example was provided, showing lots of recombination hotspots, and coldspots, across the length of the chromosome space.
We started to talk about the molecular mechanism of homologous recombination on Thursday and I discussed things a bit differently than the treatment in the book. Understanding the molecular DNA-level actions and movements of DNA during recombination has been a central area of genetics research for decades. This was an area of great controversy for a very long time, until the development of the double-stranded DNA break and repair (DSBR) model was established, which has been well-accepted and experimentally supported every since. The first model was the Holliday Model which posited that the whole process began with a pair of single-stranded DNA nicks at homologous positions at the two participating DNA molecules. After nicking, reciprocal strand invasion occurred (forming Holliday or chi structure) followed by branch migration followed by endonucleolytic resolution. Though many of the details were right, the Holliday model was ultimately discounted because there was no known enzymatic activity that could cause ssDNA nicks at the same exact (homologous) sites in two DNA molecules – still nothing known to this day that can do that. The Meselson-Radding (M-R) Model modified things by suggesting that a single-stranded nick could start the process – the free end of the nicked strand (“donor strand”, gray in diagram) could then carry out strand invasion of the “acceptor” DNA molecule (pink in diagram) which would then cause a displacement loop (or, D-loop) strand from the acceptor that could undergo base-pairing with homologous sites in the invading molecule. This model was widely regarded as essentially correct, but there was still one puzzle related to recombination – gene conversion – that could not be explained by the M-R model. Gene conversion, originally only observed in certain species of fungi, is a process whereby there is allelic “conversion” during meiosis that is in opposition to predictions of basic Mendelian genetics (e.g. one ‘a’ allele is “converted” into a ‘A’ allele in the example shown). Since this phenomenon was only observed in gametes, it was presumed to be closely associated with a meiosis-specific process such as recombination. This led researchers to develop the double-strand break & repair (DSBR) model. The DSBR model has been strongly supported over the last few decades in all lab experiments and is also able to effectively account for gene conversion. At the end of the DSBR mechanism there are tracts of DNA at the end of the process where there is base pairing between nucleotides from the “donor” strand and the “acceptor” strand. There is the possibility of nucleotide mispairing between these two strands (because they originally came from different dsDNA molecules) – these mispairings are recognized by the mismatch DNA repair enzymatic machinery that ultimately removes one of the mismatching nucleotides and replaces it with a correct complementary base. Thus, there is the possibility in this DSBR path for one allele to be converted into the other allele! Since this was all worked out, we’ve come to discover that gene conversion outcomes occur much more frequently than recombinant chromosome outcomes of the molecular recombination process in virtually all eukaryotic life forms, from fungus to human.
Week 6 Sneak Peek: Next week we will quickly recap recombination, and then transition to talk about the mutation process (Ch. 12) on Tuesday. On Thursday we will talk about the molecular genetics of cancer (Ch. 13), and how yeast (a single-celled organism…) provided key insights into the genetic underpinnings of cancer in humans.
Tuesday was the first midterm – we are about halfway done with grading and aim to return them to students next week during lecture.
On Thursday, we moved into the world of mammalian and human chromosome biology, discussing some basic terminology and conventions used in karyotype studies. We discussed some interesting chromosome evolution stories in the human lineage, demonstrating the utility of nonrecombining chromosomes (e.g., Y) for certain genetic applications. We learned about methods for studying chromosome biology, such as chromosome painting and G-banding. After the not-thinking break, we started to move into the topic of recombination…
Week 5 preview: The upcoming week will be dedicated to the topic of recombination, linkage, and gene mapping. We will cover chapter 4 – make sure you look at the material ahead-of-time. It is important to wear your ‘thinking caps’ for Chapter 4 material, and to be engaged in lectures and recitations.
This week we expanded our knowledge of different variations on dominance concepts (for example, incomplete dominance and codominance) and entered the world of pedigree analysis. Pedigrees are particularly useful in species (such as humans) where it is impossible or highly impractical to get the very large numbers of offspring required for the analytical approaches of Mendel. The patterns by which affected individuals appear on the pedigree provide ‘tell tale’ signs indicative of the dominance relationships of the alleles. We also entered the fun (IMO) world of epistasis where the interactions between gene products, for example in biochemical pathway contexts, can perturb the F2 dihybrid ratios away from the usual expected 9:3:3:1 for genes whose products do not interact. There are lots of different possible modifications of the 9:3:3:1 that result from epistasis, such as 12:3:1, 9:7, and 15:1. These different ratios result from different particular underlying biochemical explanations. You don’t need to memorize these, but do need to be able to reason your way to these modified ratios (and their corresponding phenotypes, genotypes) when given cross data. After our epistasis adventure, we moved into a review of mitosis and meiosis, emphasizing the dynamics of chromosomes during these cell division processes. We concluded Thursday’s lecture with an overview of sex chromosome transmission processes, and learned about nematode sex 🙂
Week 4 Sneak Peek: Of course, the main event will be the Tuesday Midterm during Week 4. Study hard! Bring your calculators! Know your probabilities! After the midterm, we will delve further into chromosome biology in Chapter 5.
This week, a study was published in Science magazine about the genetics underlying skin color in human populations. You can read a NY Times piece highlighting the research here.
#1. (3 points) The process of replication in most cellular organisms involves:
a) synthesis of a RNA product from a DNA template
b) synthesis of a protein product from a RNA template
c) synthesis of a DNA product from a DNA template
d) synthesis of a DNA product from a RNA template
#6. (3 points) You are a geneticist studying feather color in pigeons. You cross a true-breeding white pigeon to a true-breeding black pigeon. All of the F1 offspring have black feathers. You then mate F1 males to F1 females. The F2 offspring have the following phenotypic ratio 9 black : 7 white.
What genetic phenomenon is the most likely cause of this result?
a) epistasis
b) codominance
c) incomplete dominance
d) incomplete codominance
#16. In goldfish, black scales (G) are dominant to gold scales (g). A separate, independent gene controls eye shape where bubble eyes (N) are dominant to normal eyes (n). You cross a true-breeding black, normal eyed male fish with a true-breeding gold, bubble eyed female fish to create F1 offspring.
Part A. (3 points) What is the phenotype of the F1 offspring?
Part B. (4 points) If you intercross the F1 offspring to create F2 offspring, what is the probability of finding a gold, normal eyed fish in the F2 offspring?
Part C. (4 points) If you genotype 100 F2 fish, how many do you expect to have the genotype GgNn?
#20. You are studying a species of sea cucumbers and analyzing seven unlinked genes, each having two alleles that demonstrate simple dominant/recessive relationships, with no epistasis. You set up the following cross:
AaBbCcddEeFFGG X aabbccDdeeFfGG
Part A. (4 points) How many of the seven phenotypes are shared by the two cucumbers in the above cross?
Part B. (5 points) What is the probability of an F1 progeny of the following genotype?:
aaBbCcDdEeFFGG
A link to a pretty good YouTube video about the basics of Mendelian genetics can be found here. Lasts about 15 minutes.
Today in class, we will focus a lot on experimental methods for studying DNA in the lab. One major technique we will explore is the polymerase chain reaction (PCR). We will watch a video in class; am posting it here too in case students want to review the video. Enjoy!
I will create blog posts once per week, usually on Friday afternoons. The blog will serve three main functions:
I encourage everyone to take the few minutes to visit the blog once or twice a week to help learn the material presented in lecture. There will NEVER be content found only in the blog that appears on midterms and the final. Rather, the blog serves to supplement and provide a different voice for material covered during lectures, recitations, and in the homework.
Enjoy!