ASSESSING THE RELIABILITY OF SEQUENCE BASED METHODS USED TO IDENTIFY DE NOVO GENES

Abstract

The pN/pS ratio test, the frequency of non-synonymous substitutions (pN) versus the frequency of synonymous substitutions (pS), is used to infer what type of selection is acting on certain sections of DNA within a species. Researchers attempting to identify de novo genes have suggested that if a DNA sequence has a pN/pS ratio of less than one, then that is sufficient evidence that the sequence is a functional de novo gene due to it experiencing purifying selection against nonsynonymous substitutions. We explored the hypothesis that under random mutation and chance, a deleterious translated open reading frame (ORF) can have a pN/pS value of less than one which opposes the belief that a pN/pS values of less than one for a putative de novo gene signifies functionality. In this project, we use SLiM, a forward-in-time evolutionary simulation software, along with C code, to simulate evolution of a population. Fitness of individuals was determined by assigning fitness contributions to each amino acid based on the analysis of Kosinski et al. (2020) and summing the values of amino acids within ORFs present in that individual. Due to inefficient simulation runtimes, we were unable to produce timely results that could support or refute our original hypothesis.