Evolutionary and Biomedical Insights from the Rhesus Macaque Genome

Abstract

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineagespecific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

Limitations of the rhesus macaque draft genome assembly and annotation

“…The draft rhesus assembly was described in a publication which appeared in April 2007 [1]. As with all draft sequences, there were substantial gaps in the assembly as well as sequencing errors.…”

“…How significant were these errors? Global statistics were provided in the paper describing this assembly [1]. However, these types of statistics, while providing useful general information, can leave the reader with an incorrect perception of completeness at the gene level.…”

“…To address these issues, we examined the draft genome sequence and assembly of the rhesus macaque ( Macaca mulatta ) [1], an important biomedical research model [2-8]. Like many vertebrate draft genomes, an animal was sequenced to 5-6-fold coverage using Sanger sequencing.…”

“…Like many vertebrate draft genomes, an animal was sequenced to 5-6-fold coverage using Sanger sequencing. Several different assemblers were used and their results combined [1]. The human genome assembly was used to correct errors in the rhesus assembly.…”

Computational challenges in the analysis of ancient DNA

“…Neandertal data are well suited for investigating the potential effects of having a progressively more distantly related comparison genome, since complete genome sequences are available from three great apes and several more distantly related primates. By using only the increasingly more distantly related genome sequences of human [27], chimpanzee [28], orangutan, rhesus macaque [29], mouse lemur, bushbaby and mouse [30], we gauge how many Neandertal sequences could be identified if each of these genomes was the only one that was available. We also investigated the accuracy of the observed number of pairwise nucleotide differences in each of these comparisons ([31].…”