Advantages of an Improved Rhesus Macaque Genome for Evolutionary Analyses.

ABSTRACT

The rhesus macaque (Macaca mulatta) is widely used in molecular evolutionary analyses, particularly to identify genes under adaptive or unique evolution in the human lineage. For such studies, it is necessary to align nucleotide sequences of homologous protein-coding genes among multiple species. The validity of these analyses is dependent on high quality genomic data. However, for most mammalian species (other than humans and mice), only draft genomes are available. There has been concern that some results obtained from evolutionary analyses using draft genomes may not be correct. The rhesus macaque provides a unique opportunity to determine whether an improved genome (MacaM) yields better results than a draft genome (rheMac2) for evolutionary studies. We compared protein-coding genes annotated in the rheMac2 and MacaM genomes with their human orthologs. We found many genes annotated in rheMac2 had apparently spurious sequences not present in genes derived from MacaM. The rheMac2 annotations also appeared to inflate a frequently used evolutionary index, ω (the ratio of nonsynonymous to synonymous substitution rates). Genes with these spurious sequences must be filtered out from evolutionary analyses to obtain correct results. With the MacaM genome, improved sequence information means many more genes can be examined for indications of selection. These results indicate how upgrading genomes from draft status to a higher level of quality can improve interpretation of evolutionary patterns.