Evidence for a convergent slowdown in primate molecular rates and its implications for the timing of early primate evolution Michael E. Steipera,b,c,d,1 and Erik R. Seifferte aDepartment of Anthropology, Hunter College of the City University of New York (CUNY), New York, NY 10065; Programs in bAnthropology and cBiology, The Graduate Center, CUNY, New York, NY 10016; dNew York Consortium in Evolutionary Primatology, New York, NY; and eDepartment of Anatomical Sciences, Stony Brook University, Stony Brook, NY 11794-8081 Edited by Richard G. Klein, Stanford University, Stanford, CA, and approved February 28, 2012 (received for review November 29, 2011) A long-standing problem in primate evolution is the discord divergences—that molecular rates were exceptionally rapid in between paleontological and molecular clock estimates for the the earliest primates, and that these rates have convergently time of crown primate origins: the earliest crown primate fossils slowed over the course of primate evolution. Indeed, a conver- are ∼56 million y (Ma) old, whereas molecular estimates for the gent rate slowdown has been suggested as an explanation for the haplorhine-strepsirrhine split are often deep in the Late Creta- large differences between the molecular and fossil evidence for ceous. One explanation for this phenomenon is that crown pri- the timing of placental mammalian evolution generally (18, 19). mates existed in the Cretaceous but that their fossil remains However, this hypothesis has not been directly tested within have not yet been found. Here we provide strong evidence that a particular mammalian group. this discordance is better-explained by a convergent molecular Here we test this “convergent rate slowdown” hypothesis in rate slowdown in early primate evolution. We show that molecu- primates using a two-step analysis. First, using a comprehensive lar rates in primates are strongly and inversely related to three paleontological and neontological primate dataset (Table S2), life-history correlates: body size (BS), absolute endocranial volume we modeled the evolutionary history of three phenotypic traits: (EV), and relative endocranial volume (REV). Critically, these traits body size (BS), absolute endocranial volume (EV), and relative can be reconstructed from fossils, allowing molecular rates to be endocranial volume (REV). These traits were chosen because ANTHROPOLOGY predicted for extinct primates. To this end, we modeled the evo- they are correlated with primate life history (20–22), which is in lutionary history of BS, EV, and REV using data from both extinct turn related to molecular evolutionary rates (23). Furthermore, and extant primates. We show that the primate last common an- BS, EV, and REV are much more easily estimable from fossils cestor had a very small BS, EV, and REV. There has been a subse- than are life-history variables themselves. These analyses yielded quent convergent increase in BS, EV, and REV, indicating that there ancestral reconstructions for BS, EV, and REV from the entire has also been a convergent molecular rate slowdown over primate primate radiation, enabling assessments of phenotypic and life- evolution. We generated a unique timescale for primates by pre- history changes over primate evolution. Second, we explicitly dicting molecular rates from the reconstructed phenotypic values tested whether patterns of variation in molecular rates are corre- for a large phylogeny of living and extinct primates. This analysis lated with patterns of variation in BS, EV, and REV. Molecular – suggests that crown primates originated close to the K Pg bound- rates were estimated from four large DNA-sequence datasets to- ary and possibly in the Paleocene, largely reconciling the molecular taling over 100 Mb, and these rates were correlated with BS, EV, and fossil timescales of primate evolution. and REV using phylogenetically corrected regression techniques. Finally, we joined the results of these two analyses as a mo- hen molecular rates are constant, divergence dates can be lecular clock technique. We predicted molecular rates for pri- Westimated by using fossils to calibrate “molecular clocks” (1). mates based on the BS, EV, and REV reconstruction from our However, there is great variation in molecular rates among species analysis of fossil and extant primates and our regression for- (2–7), and this phenomenon can lead to inaccurate or biased mo- mulae. In other words, we predict the molecular rates of long- lecular clock estimates. This problem has precipitated the de- extinct primates using our knowledge of their phenotypic velopment of methods that model rate variation across lineages to attributes rooted in the fossil and extant data. This is a significant date phylogenies when rates vary (8–11). These “relaxed clock” departure from the traditional method of generating molecular methods use multiple calibrations and allow rates to vary according rates using fossils as calibrations. Because our method estimates to the parameters of a model. Relaxed clock methods are especially molecular rates by using paleontological, phylogenetic, geo- appropriate for primates, because this clade exhibits large and logical, and neontological sources, we feel that it has strong systematic variation in molecular rates both within and among advantages over traditional calibration techniques. groups (e.g., the “hominoid slowdown”) (2, 4, 7, 12, 13, 14). Nev- ertheless, the application of these methods still results in large Results differences between paleontological and molecular estimates for First, we tested whether BS, EV, and REV have changed many primate groups (Fig. 1 and Table S1). This discordance is directionally over primate evolution by using a Bayesian method particularly striking for the origin of the primate crown group, to calculate the harmonic mean-likelihood values for a number because recent molecular studies suggest a Late Cretaceous esti- of models (Table 1). For all three traits, the nondirectional mate (an average of ∼82 Ma) for this event and yet the oldest crown primate fossils are ∼56 Ma old (15)—adifferenceof∼45%. Fur- thermore, studies that have statistically modeled sampling, speci- Author contributions: M.E.S. designed research; M.E.S. and E.R.S. performed research; ation, and preservation rates over the course of primate evolution M.E.S. and E.R.S. analyzed data; and M.E.S. and E.R.S. wrote the paper. are similarly consistent with an ancient origin for crown primates The authors declare no conflict of interest. (16, 17), showing that there are also wide gaps between these This article is a PNAS Direct Submission. methods and “direct reading” approaches to the fossil record. 1To whom correspondence should be addressed. E-mail: [email protected]. Here we investigate an alternative hypothesis for the dis- This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. crepancy between molecular and fossil estimates of early primate 1073/pnas.1119506109/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1119506109 PNAS Early Edition | 1of6 Downloaded by guest on September 24, 2021 Dates from the literature: Oldest fossil Avg. molecular Hominidae Great apes This study’s dates: Uncorrected EV corrected BS corrected REV corrected Old World Monkeys Cebidae Marmosets, tamarins, owl & squirrel monkeys Tarsius Tarsiers Strepsirrhini Lemurs & lorises 80 70 60 50 40 30 20 10 0 Cretaceous PALEO. EOCENE OLIGO. MIOCENE Pl-Pl Cenozoic Fig. 1. Time-scaled phylogeny depicting divergence dates for the main groups of primates. Dates along the x axis are in Ma. Average molecular clock date estimates are from six recent studies (Table S1). The fossil femur cartoon indicates the earliest paleontological crown representatives of each taxon: crown Primates and crown Haplorhini, Teilhardina asiatica, 55.8 Ma, or, less securely, slightly older Altiatlasius koulchii (15, 57, 58); crown Strepsirrhini, Sahar- agalago,37Ma(59–61); crown Anthropoidea, Biretia, 37 Ma (59); crown Catarrhini, Morotopithecus, 20.6 Ma (62), crown Cebidae, long-lineage hypothesis (63), Branisella,26–27 Ma (64); crown Cebidae, successive radiation hypothesis (65), Lagonimico (66) and others, 13.3 Ma (66, 67); crown Cercopithecoidea, Microcolobus, 9.9 Ma (68); crown Hominidae, Sivapithecus, 12.5 Ma (69). The colored circles indicate the average divergence estimates from both uncorrected and corrected methods (Table 3). Brownian-motion model was rejected in favor of a directional result alone generally supports a slowdown in molecular rates in evolution model based on an analysis of the harmonic mean- primate evolution. likelihood values using Bayes factors (SI Text and Tables S3–S6). Second, we tested for a specific relationship between BS, EV, Subsequently, we used a Bayesian method to reconstruct the and REV and molecular rates in four large DNA-sequence ancestral values for BS, EV, and REV at nodes throughout the datasets. In 10 of the 12 phylogenetically corrected regressions primate phylogeny (24) (Fig. 2 and Tables S7 and S8). This there is a significant inverse relationship between molecular rates analysis reconstructed the BS of the primate last common an- and our three phenotypic predictors: BS, EV, and REV (Fig. 3 cestor (LCA) as ∼55 g, with a small EV (2.3 cm3; cc) only slightly and Table 2). These traits explain a large proportion of the larger than the fossil plesiadapiform Ignacius (2.14 cc) (25). The variance in molecular rates. This result provides strong evidence REV of the primate LCA was reconstructed as having been that life-history correlates are related to molecular rates in pri- lower than that of any known primate, living or extinct. mates, as has been found for primates and other mammals (6, 23, fi fi We conclude that BS, EV, and REV have evolved direction- 26). Speci cally noteworthy is the nding that molecular rates ally over primate evolution. Since the primate LCA, all major are very rapid in primates with small BS and EV and low REV. primate lineages have convergently evolved higher BS, EV, and Critically, these analyses generated regression models that can be used to predict molecular rates from BS, EV, and REV data REV.