Comparative analysis of homologous sequences enables the understanding of evolutionary patterns at the molecular level, unraveling the functional constraints that shaped the underlying genes. Bioinformatic pipelines for comparative sequence analysis typically include procedures for (i) alignment quality assessment and (ii) control of sequence redundancy. An additional, underassessed step is the control of the amount and distribution of missing data in sequence alignments. While the number of sequences available for a given gene typically increases with time, the site-specific coverage of each alignment position remains highly variable because of differences in sequencing and annotation quality, or simply because of biological variation. For any given alignment-based analysis, the selection of sequences thus defines a trade-off between the species representation and the quantity of sites with sufficient coverage to be included in the subsequent analyses.