Sullivan nodded to indicate understanding, and Allison hid another mental smile. Interesting that he showed no discomfort at all with the way the conversation was headed. Of course, with the high percentage of stillborn boys on this planet, Graysons had been fanatical about prenatal care for centuries, and men were just as involved in the process (at one remove, of course! she amended) as women.
"They had no real option about that," she went on. "Not if they wanted the change to be a permanent addition to the planetary genome. But in the process, they also got an unintended mutation. Their intervention introduced a stable trinucleotide repeat on the X chromosome, which wouldnt have been a problem... except that it in turn affected one of the AGG codons." Sullivan looked blank. "AGG codons are adenine-guanine-guanine sequences that act as locks on the expansion of other trinucleotide repeats," she explained helpfully.
"Of course," Sullivan agreed. He didnt look too terribly enlightened, but he nodded for her to continue, and she punched a new command into her holo unit. The imagery changed to a color-coded schematic of nucleotidesan enormous chain composed of the color-coded letters "A," "C," "G," and "T," repeating again and again in jumbled patterns. As Sullivan watched, the image zoomed in on a single sectiontwo three-letter groups of "CGG" in yellow, green, and green, separated by an "AGG" in red, green, and green.
"Essentially, it was a very tiny change," Allison told the Reverend. "An adenine here" she touched another key, and one of the "AGG" codes flashed brilliantly "mutated to cytosine" another key, and the flashing red "A" turned into a yellow "C" and the three-letter group to its right grew suddenly into an enormous chain of the same codes, repeating again and again "which deactivated the lock and allowed unstable expansion of"
"Excuse me, My Lady," Sullivan interrupted, "but I think were drifting into deep water here. What, precisely, does that m No." He stopped and raised one hand. "Im certain that if you told me what it meant, I would be no closer to understanding than I am now. What I truly need to know, I suppose, is what the consequences of this... unstable whatever are."
"Um." Allison sipped some more tea, then shrugged.
"DNA is composed of four nucleotides, Your Grace: adenine, cytosine, guanine, and thymine. They link together in thousands of repeatscodes, if you willwhich combine to carry the blueprint for our bodies... and transmit it to the next generation. They link in groups of three, hence the term trinucleotide, which usually occur in runs of thirty or less, but there are several diseases, such as the one we call Fragile X, in which the number of repeats expands enormously, often into the thousands, effectively... well, scrambling a portion of the master code, as it were. Are you with me so far?"
"I believe so," he said cautiously.
"All right. This schematic represents a portion of the nucleotidesin this case cytosine, adenine, and guaninefrom the Grayson genome. This trinucleotide here" she touched her controls and the holo reverted to its original form with the "AGG" flashing once more "is what we call a lock, sort of a blocker to prevent the CGG repeats on either side of it from expanding in a way that would scramble the code. What happened, though, was that when the adenine mutated into cytosine, the lock disappeared... and that allowed an unstable expansion of the CGG chain downstream of it."
"I wont pretend to understand completely, My Lady," Sullivan said after a moment, "but I believe I understand the process, in general terms at least. And just how serious a problem is this unstable expansion?"
"Well, in Fragile X, the consequence isor was, before we learned to repair itmoderate mental retardation. But what resulted here was worsemuch worse. It destroyed a portion of the chromosome necessary for early embryonic development."
"Which means, My Lady?" Sullivan asked intently.
"It means that it produced an embryonic lethal mutation in males, Your Grace," Allison said simply.
This time the Reverend came bolt upright in his chair, and she nodded to the display still glowing above the coffee table.
"Any male embryo with this mutation cannot be carried to term," she said. "Female embryos each have two X chromosomes, however, which gives them the chance for an extra copy of the destroyed gene. And the lyonization process, which inactivates one X chromosome in a female, almost always inactivates the structurally damaged one in cases like this, which means that, unlike males with the same problem, they survive."
"But in that case" Sullivan stared into the holo for several seconds, then looked back at Allison. "If I understand you correctly, My Lady, youre saying that no male child with this mutation could live?" She nodded. "In that case, how could our ancestors possibly have survived? If everyone who received the benign mutation also received this one, then how were any living male children born at all?"
"The two mutations are linked in that they were both introduced by the same vector, Your Grace, but thats the only linkage between them. Everyone got the intended mutationwell, thats probably an overstatement. Lets say that everyone who survived got the intentional one, but the unintentional one, fortunately, had incomplete penetrance. That means that thirty percent or so of the males didnt express the mutation and so survivedbut even those who survived could be carriers. To use the Fragile X analogy again, the fragile site from that disease is seen in forty percent of the cells of affected males, but carriers may not show the fragile site at all."
"I... see," Sullivan said very slowly.
"There was nothing anyone could have done about it, Your Grace. The original modification was essential if your people were to survive at all. It had to be made, and even assuming that any of the original med team were still alive by the time the harmful side effect began to manifest, and even assuming that they still had the technical capability for genetic level examinations, it was too late to do anything about it," Allison said quietly, and sat back to wait.
"Sweet Tester," Sullivan murmured at last, his voice so soft Allison hardly heard him. Then he pushed himself all the way back in his chair and inhaled deeply. He gazed at her for endless seconds, then shook himself.
"I feel certain that you must have felt very confident in your findings before you brought them to my attention, My Lady. May I also assume that your documentation of them will be sufficient to convince other experts of them?"
"Yes, Your Grace," she said positively. "For one thing, it explains the two things about your population which have most puzzled the Star Kingdoms geneticists from the beginning of the Alliance." Sullivan raised an eyebrow, and she shrugged. "Ive already mentioned the incredible rapidity with which your ancestors evolved a natural defense against heavy metals. That was number one. But a disparity in male-female birth rates on the scale of Graysons, while not all that unusual under distressed conditions, seldom lasts as long as yours has."
"I see." He gazed at her meditatively, then drank more tea. "And is there anything which can be done about this, My Lady?"
"Its really too early for me to say yes or no to that one, at least with any degree of confidence. Ive isolated two or three possible approaches, but the site of the problem may well make things difficult, because the mutated gene on the X is near the zinc-finger X protein gene. Thats a key gene in sex determination, and its at the Xp22.2" She paused as his expression began to indicate that he was lost once more.