Indels: computational methods, evolutionary dynamics, and biological applications.

Insertions and deletions (indels) constitute the second most important source of natural genomic variation. Indels make up to 25% of genomic variants in humans and are involved in complex evolutionary processes including genomic rearrangements, adaptation and speciation. Recent advances in long-read sequencing technologies allow detailed inference of indel variation in species and populations. Yet, despite their importance, evolutionary studies have traditionally ignored or mishandled indels due to a lack of comprehensive methodologies and statistical models of indel dynamics. Here we discuss methods for describing indel variation and modeling insertions and deletions over evolutionary time. We provide practical advice for tackling indels in genomic sequences and illustrate our discussion with examples of indel-induced effects in human and other natural populations, and their contribution to evolutionary processes. We outline promising directions for future developments in statistical methodologies that would allow researchers to analyze indel variation and their effects in large genomic datasets and to incorporate indels in evolutionary inference.