Title: Reconsidering the Significance of Genomic Word Frequencies 1 2 Short Title: Genomic Word Frequencies 3 4 Introduction

NOTICE: this is the authors' version of a work that was accepted for publication in Trends in Genetics. Changes resulting from the publishing process such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Abstract 1 By conventional wisdom, a feature that occurs too often or too rarely in a genome can indicate a 2 functional element. To infer functionality from frequency, it is crucial to precisely characterize 3 occurrences in neutrally evolving DNA. We find that the frequency of oligonucleotides in a 4 genomic sequence follows primarily a Pareto-lognormal distribution, which encapsulates 5 lognormal and power-law features found across all known genomes. Such a distribution may be 6 the result of completely random evolution by a copying process. Our characterization of the 7 entire frequency distribution of genomic words opens a way to a more accurate reasoning about 8 their over-and under-representation in genomic sequences.