New SAT Reading Practice Test 82: Alternative Splicing

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Alternative Splicing

With James Watson and Francis Crick's landmark article on the double helical
structure of DNA now more than a half-century old, the sheer volume of knowledge
we have since amassed regarding the regulation and expression of genetic material is
staggering, and continues to expand daily. Yet for all that has been accomplished in
05 the study of genetics, there comes now and again a discovery to underscore just how
many mysteries we have yet to unravel.
Historically, we have defined a gene as a region of DNA responsible for encoding
and regulating the expression of a discrete, heritable trait. The use of?regulating?here
is of no small importance, as the protein-coding sequence itself represents only a
10 fraction of the DNA contained within a given gene. A "promoter" region, for instance,
does not directly contribute to the mRNA transcript, but instead provides binding sites
for transcription factor proteins, and functions as sort of an "on" or "off" switch for
the expression of the gene's corresponding trait. Similarly, "silencer" and "enhancer"
regions can also bind regulatory proteins, and help to fine-tune the precise degree to
15 which a gene will be expressed under various circumstances and in response to varying
stimuli. However, perhaps the most implicitly fascinating non-coding regions of
DNA are those embedded within the protein-coding region itself.
During transcription, nucleotides are polymerized into a strand of mRNA whose
sequence is complementary to that of the template DNA. This "pre-mRNA" typically
20 contains several regions of non-coding material, or "introns," that must be excised
prior to translation of the protein-coding regions, which are referred to as "exons." In
a complex process known as?splicing,?the introns are removed and degraded, while the
adjacent ends of exons are adjoined, and trafficked out of the nucleus to the endoplasmic
reticulum, where protein synthesis can at last begin.
25 Predictably, mutations that affect a gene's splicing pattern may precipitate severe
functional impairments to its encoded protein, and some studies have estimated that
as many as half of all disease-causing mutations in humans—including those responsible
for Alzheimer's disease, Parkinson's disease, and certain forms of cystic fibrosis—
are ultimately a result of altered splicing. Furthermore, an increasing body of research
30 has also reported patterns of altered splicing in a wide variety of cancer cells, though
it remains to be seen as to whether these changes contribute to oncogenesis, or are
simply symptomatic of dysregulated growth.
With such grim potential for genetic misstep, one might wonder how evolution
could have ever favored the development of such a precarious and seemingly superfluous
35 system of gene expression in the first place. The answer to this lies in the fact that
alternative splicing patterns are not exclusively pathological, but can and do occur
under physiological circumstances as well. That is to say, through tightly controlled
changes to the differential removal of introns and retention of exons, two identical
strands of pre-mRNA can, ultimately, code for two entirely different proteins.
40 Calcitonin gene-related peptide, or CGRP, was among the first proteins identified as
a product of physiological alternative splicing. Whereas calcitonin is a well-known
hormone produced by the medullary cells of the thyroid gland, and is involved in the
regulation of calcium levels in the blood, CGRP is believed to mediate pain sensations
within central and peripheral neurons. Despite their unique structures and vastly differing
45 functions, both proteins are nonetheless encoded by the same gene.
The discovery of physiological alternative splicing came as a challenge to our traditional
understanding of genes, which held that each coding region was responsible
for the expression of a single protein. Today, of course, we know this line of thought
to be an elegant but erroneous oversimplification. Scientists have demonstrated that
50 the vast majority of animal genes participate in alternative splicing to one extent
or another; far from a mere biochemical curiosity, it is a vital biological strategy to
maximize the economy of genetic material, which must be laboriously reproduced
with each cell division, while maintaining an immense diversity in the protein-encoding
capacity of a genome. In an extreme example, the genome of the insect species
55 Drosophila melanogaster contains about 15,000 genes. Yet, through alternative splicing,
one single D melanogaster gene—known as DSCAM—has been shown to encode
about 38,000 different proteins.

The table illustrates the corresponding exons for the pre-mRNA transcipt and nine alternative splicing isoforms of the the α-tropomyosin gene.

mRNA Splicing Isoforms of α-tropomyosin

1. What is the overall purpose of this passage?

  • A. To make an argument
  • B. To introduce a topic
  • C. To present opposing views
  • D. To give medical advice

2. The first paragraph of the essay (lines 1-6) primarily serves to

  • A. pay homage to the great scientists who made the discoveries highlighted in the passage.
  • B. put the subject of the passage in a wider context.
  • C. illustrate how little is known about a particular topic.
  • D. express the optimism the author has toward scientific advancement.

3. As used in line 3, the word "amassed" most closely means

  • A. inquired.
  • B. fused.
  • C. accumulated.
  • D. weighed.

4. As used in line 20, the word "excised" most closely means

  • A. removed.
  • B. translated.
  • C. coded.
  • D. mutated.

5. Lines 29-32 ("Furthermore . . . growth.") most strongly suggest that the author of the passage believes that scientific thinking regarding the contribution of altered splicing to cancer is

  • A. malignant.
  • B. skeptical.
  • C. assured.
  • D. unsettled.

6. Based on lines 54-57, which expression gives the most likely range of values for the total number of proteins in a Drosophila melanogaster genome?

  • A. Number of total proteins = 15,000 + 38,000
  • B. Number of total proteins = 38,000 - 15,000
  • C. Number of total proteins ≤ 38,000 × 15,000
  • D. Number of total proteins > 38,000 / 15,000

7. Which of the following statements accurately describes the relationship between the pre-mRNA and all the other isoforms portrayed in the table?

  • A. The pre-mRNA is spliced into the different isoforms in the sequence provided from top to bottom.
  • B. The other isoforms represent alternative splicing patterns derived from the original pre-mRNA.
  • C. The pre-mRNA represents a combination of the other isoforms' exons when they mutate during cellular reproduction.
  • D. The other isoforms use alternative splicing to create the given sequence of pre-mRNA.

8. Which option gives the best evidence for the answer to the previous question?

  • A. Lines 10-13 ("A ‘promoter' . . . trait")
  • B. Lines 13-16 ("Similarly . . . stimuli")
  • C. Lines 18-19 ("During . . . DNA")
  • D. Lines 37-39 ("That is . . . proteins")

9. Scientists who thought along the lines outlined in lines 49-54 ("Scientists . . . genome") would most likely have what opinion about the information in the given table?

  • A. Supportive, because it demonstrates how alternative splicing can help maximize the economy of genetic material.
  • B. Supportive, because it shows the process whereby mRNA transforms into a potential variety of isoforms.
  • C. Unsupportive, because this data illustrates the potential pitfalls, such as cancerous mutations, associated with alternative splicing.
  • D. Unsupportive, because it mentions exons but ignores introns and their deletion during the alternative splicing process.

10. Based on the passage, what would someone who believed in the first historical theory of DNA most likely think would be the number of unique protein transcripts that would result from the replication of the α-tropomyosin gene outlined in the table?

  • A. 1
  • B. 3
  • C. 9
  • D. 12 or more

11. Which option gives the best evidence for the answer to the previous question?

  • A. Lines 1-4 ("With . . . daily")
  • B. Lines 4-6 ("Yet for . . . unravel")
  • C. Lines 29-32 ("Furthermore . . . growth")
  • D. Lines 46-48 ("The discovery . . . protein")