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Exam 2: Fundamentals of Gene Structure, Gene Expression, and Human Genome Organization

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Question 1

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Sequence conservation analyses often use computer-based alignment of the nucleotide sequences of equivalent genes in different organisms, or of the amino acid sequences of the corresponding proteins. The alignment below shows a BLAST alignment of the first 100 amino acids of the human CFTR (cystic fibrosis transmembrane receptor) protein (shown as the Query) and the equivalent sequence in the corresponding mouse protein (shown as Sbjct, an abbreviation of subject). The intervening middle line shows whether at the same position in the two sequences the amino acids are identical or chemically similar. Query 1 MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLSEKLEREWDRE 60 MQ+SPLEKAS +SKLFFSWT PILRKGYR LELSDIYQ PS DSAD+LSEKLEREWDRE Sbjct 1 MQKSPLEKASFISKLFFSWTTPILRKGYRHHLELSDIYQAPSADSADHLSEKLEREWDRE 60 Query 61 LASKKNPKLINALRRCFFWRFMFYGIFLYLGEVTKAVQPL 100 ASKKNP+LI+ALRRCFFWRF+FYGI LYLGEVTKAVQP+ Sbjct 61 QASKKNPQLIHALRRCFFWRFLFYGILLYLGEVTKAVQPV 100 Calculate (a) the degree of sequence identity for the aligned sequences (b) the degree of sequence similarity.

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a) Sequence identity = the number of per...

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Question 2

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Which, if any, of the following statements is false?

A) Unlike DNA, RNAs are unmethylated, and only the four standard bases - A, C, G and U - are found in RNAs.
B) The primary structure of an RNA is the linear sequence of nucleotides.
C) The secondary structure of an RNA is dominated by hydrogen bonding between bases on the same strand.
D) Stem-loop structures are common in RNA and consist of complementary sequences that form stable base pairs, separated by a short sequence of unpaired bases.

E) All of the above
F) C) and D)

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Question 3

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Regarding protein structure, which, if any, of the following statements is incorrect?

Four different levels of protein structure are recognized. What are they? Illustrate your answer with examples, wherever possible.

Fill in the blanks below. Retrotransposon repeats account for just over ___1___ % of our genome and are classified into three broad families. One family resembles a class of RNA virus, known as a ___2____. Like a ___2____, they contain direct repeats at their ends, known as ___3____ ____4____ repeats, and full-length family members have the same gene structure as a simple ____2____. A second family of retrotransposon repeats, known as ____5____ , has some full-length copies with sizes of 6-8 kb, and like the retrovirus-like family some of them are able to make a specialized DNA polymerase known as _____6____ ____7_____. A third family of retrotransposon repeats, known as ___8____, have short full-length sequences of between 100 and 300 bp, and are exemplified by ___9____ repeats, the most prolific DNA sequence in the human genome, with a copy number of more than ____10____ ____11_____ repeats. Only a small fraction of the retrotransposon repeats can actively transpose (most are truncated copies or have ____11_____ mutations). ___8____ repeats and other _____8_____ are unable to make a ____6____ ____7_____ but very occasionally do transpose using a ____6____ ____7_____ produced by another retrotransposon.

Which, if any, of the following statements are false? a) Constitutive heterochromatin remains highly condensed throughout the cell cycle. b) Unlike constitutive heterochromatin, facultative heterochromatin describes chromatin that can de-condense and behave as euchromatin under certain circumstances. c) Most of the long arm of the Y chromatin is made up of constitutive heterochromatin. d) In women one of the two X chromosomes in each diploid cell is heterochromatinised.

Which, if any, of the following statements are false?

Illustrate, with examples, how noncoding RNAs are more than ubiquitous general regulators of transcription or protein synthesis.

Which, if any, of the following statements are false?

Fill in the blanks below with single words. When a gene is expressed, the two DNA strands are locally unwound to allow access by the ____1_____ machinery. One of the DNA strands serves as a ____2____ for an RNA polymerase to synthesize a complementary RNA. The initial transcript, often called the ____3____ transcript, is identical in base sequence (except that U replaces T) to the sequence of the other DNA strand, which is known as the ____4____ strand (and so the opposing strand that serves as the ___2____ is also known as the ____5____ strand). The segment of genomic DNA that corresponds to the ____3____ transcript is known as the ___6___ ___7____.

In some gene families the genes are clustered in defined chromosomal regions as a result of ___1____ gene duplication. That often occurs as a result of misalignment of chromatids: over a limited chromosomal region, the DNA sequences are paired but out of register. Subsequent ___2_____ in the mispaired region can generate chromatids with two copies of a gene. Successive gene duplications results in a cluster of highly related genes. Not all the gene copies are functional: some acquire inactivating mutations to become a type of ____3_____ known as a _____4_____ ____3____. In other gene families there may be up to many hundreds of more members scattered across the genome. They often have large numbers of ____5____ ____3______ , also known as ____6_____ that arose by copying the RNA transcripts of a functional gene using a ____7____ _____8_____ to make cDNA copies that integrated into the genome at other locations but subsequently acquired deleterious mutations.

What is the type of natural selection that is responsible for strong evolutionary conservation of functionally important DNA sequences, and how does it work?

Fill in the blanks below. During gene expression, the initial RNA transcript needs to undergo processing to make a mature RNA, either a ____1____ RNA or a ____2___ RNA. For many of our genes, the initial RNA transcript needs to be cleaved into pieces. Some of the pieces, called ____3____, are discarded, but other alternating pieces called ___4____ are retained and fused in the same linear order as their order when transcribed. The junctions between ___4____ and ____3____ contain some highly conserved nucleotides, notably a ____5____ dinucleotide at the beginning of ___3____ and an ___6____ dinucleotide at the ends of ____3____. For ____4_____ and _____3_____ the original definitions have been broadened to include the corresponding segments of _____7_____ ____8______

What is the total DNA content of (a) our genome; (b) an average human chromosome; (c) the human mitochondrial genome?

Roughly what percentage of our genome is made up of coding sequence?

The endosymbiont hypothesis can explain why we have two very different genomes in our cells. What does it propose?

Describe the DNA composition of the centromeres of our chromosomes. To what extent are these DNA sequences conserved between different chromosomes, and to what extent do they resemble the sequences of centromeres in other organisms?

What is the purpose of RNA splicing? Why do some of our genes not undergo RNA splicing?

Fill in the blanks below. Our genome has numerous identical or similar copies of certain DNA sequences. Some of these are ____1____ ____2______, neighboring duplicated segments that are more than 1 kb in length (and often much larger), and that show more than 90% sequence identity, having duplicated very recently during evolution. Many of our genes are present in multiple copies that are collectively known as ____3_____ ____4_____ (and often contain both functional gene copies and ____5______ ). They arose by a slow process of intermittent gene duplication over sometimes long periods of evolutionary time. Extremely similar gene copies, such as the two human ___6____ - globin genes that make identical proteins, arose by evolutionarily recent gene duplications. More distantly related gene copies generally arose from comparatively ___7___ gene duplications.

What is the approximate ratio between the DNA content of our nuclear genome and our mitochondrial genome?