Multiple orthogonal polynomials with respect to two weights on the step-line are considered. A connection between different dual spectral matrices, one banded (recursion matrix) and one Hessenberg, respectively, and the Gauss–Borel factorization of the moment matrix is given. It is shown a hidden freedom exhibited by the spectral system related to the multiple orthogonal polynomials. Pearson equations are discussed, a Laguerre–Freud matrix is considered, and differential equations for type I and II multiple orthogonal polynomials, as well as for the corresponding linear forms are given. The Jacobi–Piñeiro multiple orthogonal polynomials of type I and type II are used as an illustrating case and the corresponding differential relations are presented. A permuting Christoffel transformation is discussed, finding the connection between the different families of multiple orthogonal polynomials. The Jacobi–Piñeiro case provides a convenient illustration of these symmetries, giving linear relations between different polynomials with shifted and permuted parameters. We also present the general theory for the perturbation of each weight by a different polynomial or rational function aka called Christoffel and Geronimus transformations. The connections formulas between the type II multiple orthogonal polynomials, the type I linear forms, as well as the vector Stieltjes–Markov vector functions is also presented. We illustrate these findings by analyzing the special case of modification by an even polynomial.