BIS 101

Fun with three linked loci: recombination rates and map distances
Michael Turelli

Suppose we have three diallelic loci, creatively named locus A, locus B and locus C. These loci are
linked with B between A and C. At each locus, there is a recessive allele; these alleles are denoted
(surprise!) a, b and c. We start with two pure-breeding lines with genotypes AABBCC and aabbcc,
produce an F1, then test-cross the F1 to the triple recessive parental stock. By examining the resulting
progeny, we can directly assess the gametes produced by meiosis with recombination in the triple
heterozygote F1, ABC/abc.

As usual, we expect eight distinct gametes that fall into four classes. In each of these four classes, the
two complementary gametes are expected to be equally frequent.

The four classes are:

C∅, the parental (non-recombinant) class, corresponding to gametes: ABC and abc;
Cab, recombinant only between loci A and B, corresponding to gametes: Abc and aBC;
Cab, recombinant only between loci B and C, corresponding to gametes: ABc and abC;
Cabc, double recombinant, corresponding to gametes: AbC and aBc.

We assume that the fraction of gametes falling into class Ci is Pi, with P∅ + Pab + Pbc + Pabc = 1.

Let rab denote the recombination rate between loci A and B, let rbc denote the recombination rate
between loci B and C, let rac denote the recombination rate between loci A and C, and let rabc denote the
double recombination rate between loci A, B and C.

By the definition of “recombination rate,” we have the following identities:

rab = Pab + Pabc, (1a)
rbc = Pbc + Pabc, (1b)
rac = Pab + Pbc, and (1c)
rabc = Pabc. (2)

Adding equations (1a) and (1b), then looking at (1c) and (2), we see that for any level of pairwise and
double recombination,

rac = rab + rbc – 2rabc; or equivalently (3a)

rabc = (½)(rab + rbc – rac). (3b)

If there is no interference, rabc = rabrbc and rac = rab(1 – rbc) + (1 – rab)rbc. (4)
Obviously, these identities are consistent with (3).

Application to map distances: We see immediately from (3) that recombination rates are additive
(i.e., rac = rab + rbc) only over intervals (locus A to locus C) in which double recombination events do not
occur, i.e., rabc = 0. In fact, geneticists build genetic maps using marker loci sufficiently close that
double recombination can be ignored. Once you have a scaffold of markers, you just fill in additional
loci as they become available. Map distances correspond to recombination rates only over distances
that are short enough that double recombinants occur with negligible frequency.