Using Alu Elements to Identify Orthologous Chromosomes Across Primates

Abstract

Orthologous chromosome identification provides a basis for detecting the chromosomal locations of various genes between species. In non‐human primates, this information is instrumental to model organism research and pharmacogenetics. Thus far, ascertaining orthologous chromosome pairings between primate species has been constrained by resource and time‐intensive biochemical or bioinformatic approaches. As such, current methods have had only limited progress in identifying orthologous chromosomes in primates. Large‐scale genetic sequence analysis remains impractical, largely due to the computational overload associated with simultaneously analyzing millions of nucleotides. As such, an accurate and efficient strategy to identify orthologous chromosomes remains to be developed. Such a strategy would ideally compare short, rapidly diverging genetic sequences that originated preceding speciation. In addition, these sequences should be easily distinguishable from surrounding DNA, have a unidirectional mode of evolution, and be homoplasy‐free. These characteristics best describe Short Interspersed Nuclear Elements (SINEs). Yet, comparative analysis of primate SINEs has traditionally been limited to a binary state, detecting merely the presence or lack of a specific transposable element. Here, we propose a novel strategy to identify orthologous chromosomes in primates by analyzing the divergence of Alu sequences, a ubiquitous primate SINE. Alu elements were first obtained from the University of California Santa Cruz Genome Table Browser for 11 distinct primate species. Each parent sequence in a given species was then aligned using the Smith‐Waterman algorithm to all other sequences of the same subfamily in a second species. The sequence with the highest Smith‐Waterman score was assigned to be homologous to the parent sequence. The chromosome number of the parent and homologous sequences were recorded. After over 5 million sequences were analyzed, the results were tabulated to determine which chromosomes had the highest frequency of homologous pairings across any two compared primate species. This approach allowed us to determine orthologous chromosomes between two primates with a minimum z score of 2.5 (p < 0.007) and regularly above 4 (p < 1e–4). A sample of our results was compared with previously published lists of orthologous chromosomes, and a near‐perfect match verified the validity of our methodology. Our next goal is to generate a publicly available interactive repository of primate orthologous chromosome pairings.