by Sarah Bagby
Answer: FLAGSHIP
Problem: Arbor Day Town/​Bloomsday Town

Solvers are presented with eight sets of two or three clues, and a “sequence library” containing 26 numbered 13-nucleotide sequences. The first clue in each set begins “Number of . . .”; the second or third in each set looks initially like a biological trivia question, but ends in a citation to an unknown reference from a given year. The portion of the trivia clue that’s given is woefully underspecified; clearly, you need to know what the reference is to solve the clue.

Path to solution:

  1. Notice which references are used: in order, refs. 16, 21, 2, 13, 5, 4, 9, and 4 again. In the standard alphanumeric mapping, this spells PUBMED ID: the unique 8-digit number assigned to each research paper deposited in the National Library of Medicine’s repository, PubMed.
  2. Figure out how to turn what you’ve been given into PubMed IDs (PMIDs). The flavortext and title provide hints: taking A = 0, C = 1, G = 2, T = 3 (ordering: “A cool green tree. A cozy grove. Tea.”), each sequence in the library can be translated to an integer represented in base 4 (quaternary; hinted by the puzzle title) and then converted to base 10. (“Back to basics” and “10-4” in the flavortext are additional hints at base shenanigans.) As confirmation, you should find that the publication years given in the clues match up to the papers with the corresponding PubMed IDs.
  3. Use the cited papers to solve the underspecified clues. This should be straightforward; in every case, the title or abstract of the paper referenced supplies the needed information. Thus, for instance, PMID 26066833 is a paper titled “The 4G/4G Genotype of PAI-1 Polymorphism Is Associated with Higher Plasma PAI-1 Concentrations and Mortality in Patients with Severe Sepsis”; the allele present in two copies in the patients studied here is 4G. (What of the sequences in the sequence library that aren’t referenced by clues? These are also valid PubMed IDs, each to a different paper whose title includes the phrase “red herring.”)
Resolution Clue Sequence in library As base 4 As base-10 PMID Answer
3.3Å Number of ATP produced (theoretical maximum, to the nearest integer) per respiratory NADH oxidation 3
Chirality of amino acids incorporated into proteins by ribosomes L
Homozygous allele in ref. 16 (2015) CGATCGTTTGCAC 1203123332101 26066833 4G
2.05Å Number of carbons transferred to THF by EC 6.3.4.3 1
Method of approximation applied to rare events in ref. 21 (2018) CTAGTCAACTTTG 1302310013332 30097918 WKB
1.45Å Number of net positive charges transferred to the extracellular space by the Na+/K+ ATPase 1
rRNA region sequenced in ref. 2 (2018) CTATGTGGGATCT 1303232220313 30337591 V4
Heaviest atom in the moiety transferred by a kinase P
2.9Å Number of pyruvate produced per glucose entering glycolysis 2
Enzyme studied in ref. 13 (2015) CGAAGGTTGGTAA 1200223322300 25345712 PME
3Å Number of CO2 molecules released in each turn of the Krebs cycle 2
Plant gene studied in ref. 15 (2012) CCCTAGAGCCGTT 1113020211233 22841711 ZR3
2.85Å Number of residues whose sidechains contribute to serine protease catalysis 3
Type of damage found to promote HK2 pyroptosis in ref. 4 (2016) CGGGTCCGCGAAC 1222311212001 28006785 HRI
1.8Å Number of ATP required per DNA ligase turnover 1
First base of the amber, ochre, and opal codons U
Brain region whose connectivity is found to be reorganized in ref. 9 (2013) CCGGAAAAATATG 1122000003032 23593166 DZ
1.9Å Number of carbons in either product of the second Calvin cycle reaction catalyzed by transketolase 5
Mammalian chromosome whose activity is modulated by dosage compensation X
Family of genes whose 18 and 1β forms’ response to a microRNA is measured in ref. 4 (2016) CGGGTCCGCGAAC 1222311212001 28006785 IL
  1. String together each set’s answers to form a four-character Protein Data Bank (PDB) ID (e.g., 3L4G), i.e., a unique identifier for the crystal structure of a particular protein. The nature of these identifiers is clued both by the puzzle title (quaternary structure is a level of protein organization) and by the notation that heads each set of clues, which gives the resolution to which that crystal structure has been solved (e.g., 3.3Å). Googling a PDB ID, independent of other information, should bring up the appropriate record in the PDB.
  2. Look up the PDB IDs. In all cases, the proteins referenced are aminoacyl-tRNA synthetases, the class of enzymes that charge tRNAs with their cognate amino acids. Each of these enzymes is specific for just one amino acid; in the time-honored fashion of biology puzzles, the thing to do is to represent that amino acid by its single-letter code and read off the answer FLAGSHIP.
PDB ID Enzyme Amino acid code
3L4G phenylalanyl-tRNA synthetase F
1WKB leucyl-tRNA synthetase L
1V4P alanyl-tRNA synthetase A
2PME glycyl-tRNA synthetase G
2ZR3 seryl-tRNA synthetase S
3HRI histidyl-tRNA synthetase H
1UDZ isoleucyl-tRNA synthetase I
5XIL prolyl-tRNA synthetase P