Large-scale analysis of Macaca fascicularis transcripts and inference of genetic divergence between M. fascicularis and M. mulatta

Itsuro Inoue,Yosuke Kameoka,Yutaka Suzuki,Katsuyuki Hashimoto,Sumio Sugano,Yasuhiro Uno,Ichiro Takahashi,Munetomo Hida,Jun Kusuda,Makoto Hirata,Reiko Tanuma,Keiji Terao,Naoki Osada

doi:10.1186/1471-2164-9-90

Abstract

BackgroundCynomolgus macaques (Macaca fascicularis) are widely used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as rhesus macaques (M. mulatta). We isolated 85,721 clones and determined 9407 full-insert sequences from cynomolgus monkey brain, testis, and liver. These sequences were annotated based on homology to human genes and stored in a database, QFbase .ResultsWe found that 1024 transcripts did not represent any public human cDNA sequence and examined their expression using M. fascicularis oligonucleotide microarrays. Significant expression was detected for 544 (51%) of the unidentified transcripts. Moreover, we identified 226 genes containing exon alterations in the untranslated regions of the macaque transcripts, despite the highly conserved structure of the coding regions. Considering the polymorphism in the common ancestor of cynomolgus and rhesus macaques and the rate of PCR errors, the divergence time between the two species was estimated to be around 0.9 million years ago.ConclusionTranscript data from Old World monkeys provide a means not only to determine the evolutionary difference between human and non-human primates but also to unveil hidden transcripts in the human genome. Increasing the genomic resources and information of macaque monkeys will greatly contribute to the development of evolutionary biology and biomedical sciences.

Highlights

Cynomolgus macaques (Macaca fascicularis) are widely used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as rhesus macaques (M. mulatta)
When we limited the human reference genes to the validated protein-coding genes (i.e., RefSeq accession beginning with NM), 47% of the human reference genes were represented in the macaque cDNAs
After filtering the ambiguous entries, in the untranslated region (UTR) of macaque cDNAs, we found 262 exons that were not found in the human cDNA

Summary

Introduction

Cynomolgus macaques (Macaca fascicularis) are widely used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as rhesus macaques (M. mulatta). Genomic resources and information about primates are valuable for evolutionary and biomedical studies to determine how and why phenotypes specific to humans, as well as human diseases, have been formed They are important for extrapolating the results of laboratory experiments to medical research because the physiology of primates is more similar to that of humans as compared with other common experimental animals such as rodents. The cynomolgus macaque (Macaca fascicularis), known as the long-tailed or crab-eating macaque, is an Old World monkey living in Southeast Asia It is bred in laboratories worldwide and is one of the most popular primates used for laboratory animal studies, such as those on infectious diseases, immunology, pharmacology, tissue engineering, gene therapy, senescence, and learning [1]. The US government funded genome sequencing of the rhesus macaque because it is the most common laboratory animal bred in the US, and in 2007, the draft sequence of the rhesus macaque was published [5]

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