The common marmoset genome provides insight into primate biology and evolution

Abstract

We report the whole-genome sequence of the common marmoset (Callithrix jacchus). The 2.26-Gb genome of a female marmoset was assembled using Sanger read data (6×) and a whole-genome shotgun strategy. A first analysis has permitted comparison with the genomes of apes and Old World monkeys and the identification of specific features that might contribute to the unique biology of this diminutive primate, including genetic changes that may influence body size, frequent twinning and chimerism. We observed positive selection in growth hormone/insulin-like growth factor genes (growth pathways), respiratory complex I genes (metabolic pathways), and genes encoding immunobiological factors and proteases (reproductive and immunity pathways). In addition, both protein-coding and microRNA genes related to reproduction exhibited evidence of rapid sequence evolution. This genome sequence for a New World monkey enables increased power for comparative analyses among available primate genomes and facilitates biomedical research application.

Figure 1. Predicted let-7 Regulated Genes (miRNA targets)

The number of protein coding genes with predicted targets for let-7 miRNA binding in the 3′ UTR are shown. Only single copy orthologs are counted and numbers are relative to the number found in human (100% on scale). The number of gene targets shared with human (in blue) falls as the evolutionary distance increases, as expected. However, the proportion of let-7 targets shared with human is comparable for marmoset, dog, horse and cow, while mouse and rat share fewer targets with human than other non-primate placental mammals.

Figure 2. Gains and Losses of let-7 Regulated Genes

The conserved let-7 miRNA targets variable numbers of genes. Let-7 targets gains (in green) and losses (in blue) mapped to the phylogenetic tree of the analyzed species, line thickness indicates the rate of gain or loss. Gains and losses that occurred twice on independent lineages were omitted. Gains exceed losses on each branch of the tree, and the total gained (196) is four times the losses (49). Primate lineage changes (gains plus losses) exceed non-primate lineage changes (except for the branch leading to rat after divergence from mouse).

Figure 3. Residues under Positive Selection in IGF1R

The insulin-like growth factor 1 receptor (IGF1R) interacts with other genes in growth hormone pathways and has a role in both prenatal (left) and postnatal (right) growth. Genes in these pathways in marmoset that have residues under positive selection are tallied, the number changes that can be assigned to either the marmoset or callitrichine NWM lineages are also shown. In the middle, the first three domains of the IGF1R alpha chain are shown with positively selected residues in red (Bayes empirical Bayes analysis PP>0.95) and yellow (PP>0.5). Leucine-rich repeat domains L1 and L2 are shown in green with L1 on top, cystein-rich region CR is shown in blue. A multiple alignment of IGF1R proteins from several mammalians species (bottom) exhibits several marmoset changes in a short region corresponding to the part of structure enclosed in the black rectangle.

Figure 4. Twinning species and WFIKKN1 sequence variation

Primate species tree showing species that regularly produce twins in green and those that produce singletons in blue or purple. Phylogeny from. In the table, marmoset WFIKKN1 NS changes sequenced labeled by the amino acid change (T307A Chr12:642862, P to S Chr12:642877 multiple base insertion, A496V Chr12:643445, R545H Chr12:643592). R545H is predicted by SIFT to alter protein function and by Polyphen to be probably damaging. Features related to reproduction including twin offspring, pair bonding, and reproductive suppression in non-breeding females and adult female weight are shown. Adult female weights from IUCN 2013. IUCN Red List of Threatened Species. Version 2013.2. (see URLs) and Primate Info Net (apes and marmoset, see URLs). Species on the green branches exhibit phyletic dwarfing, an early period of developmental quiescence, and a shared chimeric placenta. Sequence changes in the WFIKKN1 gene support the phylogenetic tree with four changes occurring on the branch leading to tamarins and marmosets and a single change in Callimico goeldii back to the residue found in other primates that produce singletons (purple).