Primate Rates Research Articles

Reproductive Longevity Predicts Mutation Rates in Primates

Mutation rates vary between species across several orders of magnitude, with larger organisms having the highest per-generation mutation rates. Hypotheses for this pattern typically invoke physiological or population-genetic constraints imposed on the molecular machinery preventing mutations [1]. However, continuing germline cell division in multicellular eukaryotes means that organisms with longer generation times and of larger size will leave more mutations to their offspring simply as a byproduct of their increased lifespan [2, 3]. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from six multi-generation pedigrees to demonstrate that paternal age is the major factor determining the number of de novo mutations in this species. We find that owl monkeys have an average mutation rate of 0.81× 10-8 per site per generation, roughly 32% lower than the estimate in humans. Based on a simple model of reproductive longevity that does not require any changes to the mutational machinery, we show that this is the expected mutation rate in owl monkeys. We further demonstrate that our model predicts species-specific mutation rates in other primates, including study-specific mutation rates in humans based on the average paternal age. Our results suggest that variation in life history traits alone can explain variation in the per-generation mutation rate among primates, and perhaps among a wide range of multicellular organisms.

REST, a master regulator of neurogenesis, evolved under strong positive selection in humans and in non human primates

The transcriptional repressor REST regulates many neuronal genes by binding RE1 motifs. About one third of human RE1s are recently evolved and specific to primates. As changes in the activity of a transcription factor reverberate on its downstream targets, we assessed whether REST displays fast evolutionary rates in primates. We show that REST was targeted by very strong positive selection during primate evolution. Positive selection was also evident in the human lineage, with six selected sites located in a region that surrounds a VNTR in exon 4. Analysis of expression data indicated that REST brain expression peaks during aging in humans but not in other primates. Because a REST coding variant (rs3796529) was previously associated with protection from hippocampal atrophy in elderly subjects with mild cognitive impairment (MCI), we analyzed a cohort of Alzheimer disease (AD) continuum patients. Genotyping of two coding variants (rs3796529 and rs2227902) located in the region surrounding the VNTR indicated a role for rs2227902 in modulation of hippocampal volume loss, indirectly confirming a role for REST in neuroprotection. Experimental studies will be instrumental to determine the functional effect of positively selected sites in REST and the role of REST variants in neuropreservation/neurodegeneration.

Covariance between Testes Size and Substitution Rates in Primates

Understanding the causes of substitution rate variation is an important goal in the study of molecular evolution. It has been proposed that sperm competition intensity may affect genome-wide rates of substitution as a by-product of selection on sperm numbers. Here, I test this hypothesis by applying recently developed Bayesian methods to a data set consisting of approximately 35 kb of sequence data from 55 primate species. I find evidence for positive covariance between testes mass and the rate of substitution, independently of the potentially confounding effects of body mass and longevity.

Evidence for a convergent slowdown in primate molecular rates and its implications for the timing of early primate evolution

A long-standing problem in primate evolution is the discord between paleontological and molecular clock estimates for the time of crown primate origins: the earliest crown primate fossils are ~56 million y (Ma) old, whereas molecular estimates for the haplorhine-strepsirrhine split are often deep in the Late Cretaceous. One explanation for this phenomenon is that crown primates existed in the Cretaceous but that their fossil remains have not yet been found. Here we provide strong evidence that this discordance is better-explained by a convergent molecular rate slowdown in early primate evolution. We show that molecular rates in primates are strongly and inversely related to three life-history correlates: body size (BS), absolute endocranial volume (EV), and relative endocranial volume (REV). Critically, these traits can be reconstructed from fossils, allowing molecular rates to be predicted for extinct primates. To this end, we modeled the evolutionary history of BS, EV, and REV using data from both extinct and extant primates. We show that the primate last common ancestor had a very small BS, EV, and REV. There has been a subsequent convergent increase in BS, EV, and REV, indicating that there has also been a convergent molecular rate slowdown over primate evolution. We generated a unique timescale for primates by predicting molecular rates from the reconstructed phenotypic values for a large phylogeny of living and extinct primates. This analysis suggests that crown primates originated close to the K-Pg boundary and possibly in the Paleocene, largely reconciling the molecular and fossil timescales of primate evolution.

Primate Growth in the Slow Lane: A Study of Inter-Species Variation in the Growth Constant A

Primates grow and develop slowly for mammalian standards. Charnov showed that primates grow at only about 40% of the rates observed in other mammals of similar size. However, previous estimates of growth rates in primates were derived from regressions of adult body weight on age at first reproduction in different species, and therefore represent only an average trend for primates. Based on Charnov’s ‘growth law’, we estimated the growth constant A directly from published growth curves for 36 primate species from strepsirrhines to apes. We show that although primate growth is slow in all sampled species in comparison with the mammalian average, there is significant variation around the primate mean. Lemurids are particularly interesting due to their wide range of A values, and further study is required to determine whether environmental unpredictability could lead to the evolution of both very fast and very slow grow in different species. Results also indicate significant negative correlations between the growth constant A and both age at first reproduction and duration of the juvenile period, lending support to the juvenile risk hypothesis.

Proboscidean mitogenomics: chronology and mode of elephant evolution using mastodon as outgroup.

We have sequenced the complete mitochondrial genome of the extinct American mastodon (Mammut americanum) from an Alaskan fossil that is between 50,000 and 130,000 y old, extending the age range of genomic analyses by almost a complete glacial cycle. The sequence we obtained is substantially different from previously reported partial mastodon mitochondrial DNA sequences. By comparing those partial sequences to other proboscidean sequences, we conclude that we have obtained the first sequence of mastodon DNA ever reported. Using the sequence of the mastodon, which diverged 24–28 million years ago (mya) from the Elephantidae lineage, as an outgroup, we infer that the ancestors of African elephants diverged from the lineage leading to mammoths and Asian elephants approximately 7.6 mya and that mammoths and Asian elephants diverged approximately 6.7 mya. We also conclude that the nuclear genomes of the African savannah and forest elephants diverged approximately 4.0 mya, supporting the view that these two groups represent different species. Finally, we found the mitochondrial mutation rate of proboscideans to be roughly half of the rate in primates during at least the last 24 million years.

High rate of chimeric gene origination by retroposition in plant genomes.

Retroposition is widely found to play essential roles in origination of new mammalian and other animal genes. However, the scarcity of retrogenes in plants has led to the assumption that plant genomes rarely evolve new gene duplicates by retroposition, despite abundant retrotransposons in plants and a reported long terminal repeat (LTR) retrotransposon-mediated mechanism of retroposing cellular genes in maize (Zea mays). We show extensive retropositions in the rice (Oryza sativa) genome, with 1235 identified primary retrogenes. We identified 27 of these primary retrogenes within LTR retrotransposons, confirming a previously observed role of retroelements in generating plant retrogenes. Substitution analyses revealed that the vast majority are subject to negative selection, suggesting, along with expression data and evidence of age, that they are likely functional retrogenes. In addition, 42% of these retrosequences have recruited new exons from flanking regions, generating a large number of chimerical genes. We also identified young chimerical genes, suggesting that gene origination through retroposition is ongoing, with a rate an order of magnitude higher than the rate in primates. Finally, we observed that retropositions have followed an unexpected spatial pattern in which functional retrogenes avoid centromeric regions, while retropseudogenes are randomly distributed. These observations suggest that retroposition is an important mechanism that governs gene evolution in rice and other grass species.

Evolutionary Conservation of 5' upstream Sequence of Nine Genes between Human and Great Apes

Nucleotide sequences of nine 5' upstream gene regions for human, chimpanzee, gorilla, and orangutan were determined. We estimated nucleotide differences (d) for each region between human and great apes. The overall d was 0.027 (ranged from 0.004 to 0.052). Rates of nucleotide substitution were estimated by using d and divergence times of human, chimpanzee, gorilla, and orangutan. The overall rate of nucleotide substitution between human and other hominoids was estimated to be 0.52-0.85 x 10(-9). This rate in 5' upstream regions was lower than that of synonymous sites, suggesting that 5' upstream regions have evolved under some functional constraints. Because lower rates have been reported for coding sequences in primates compared to rodents, we also estimated the rate (1.17-1.76 x 10(-9)) of nucleotide substitutions for the corresponding 5' upstream regions in rodents (mouse/rat comparison). Thus the primate rate was lower than rodent rate also for the 5' upstream regions.

Conformal rotation therapy with central axis beam block is a feasible alternative to intensity-modulated radiotherapy for chordomas of the cervical spine

Paraspinal tumours, such as chordoma, represent a treatment challenge for oncologists, requiring high dose to the target volume without exceeding the tolerance dose of the spinal cord. Intensity-modulated radiotherapy (IMRT) is helpful in achieving sharp dose gradients and conformation of dose to the target volume. We present a simpler technique--conformal rotation therapy with a central axis beam block (CRT + BB), which can provide similar dose distributions. A patient with a cervical chordoma developed postoperative recurrence and was treated with high-dose palliative radiotherapy. Treatment was delivered using CRT + BB, with three fixed beams and three coplanar arcs. A dose of 62 Gy in 31 fractions was delivered to the 100% isodose, giving a maximum spinal cord dose of 49.6 Gy. The patient relapsed 2 years later, and was re-treated using the same technique to a dose of 57 Gy in 30 fractions. Estimates of spinal cord repair rates in primates were used to determine the tolerance dose of the spinal cord for re-treatment. The patient remained well for a further 25 months before developing local recurrence, which was treated with palliative chemotherapy. Re-treatment plans using CRT + BB and IMRT were compared. Dose-volume histograms show equivalence of dose to the spinal cord, although the IMRT plan delivered a slightly higher dose to tumour and lower dose to surrounding soft tissues. Treatment using CRT + BB requires careful planning and discussion with neurosurgeons before surgery. The normal curvature of the cervical spine must be eliminated if possible, and the patient must be immobilised with the neck horizontal. If these geometric constraints can be satisfied, then CRT + BB can be used as a safe and effective alternative treatment to IMRT for tumours at this site.

Molecular Evolution of Cytochrome c Oxidase Subunit I in Primates: Is There Coevolution between Mitochondrial and Nuclear Genomes?

Phylogenetic analyses carried out on cytochrome c oxidase (COX) subunit I mitochondrial genes from 14 primates representing the major branches of the order and four outgroup nonprimate eutherians revealed that transversions and amino acid replacements (i.e., the more slowly occurring sequence changes) contained lower levels of homoplasy and thus provided more accurate information on cladistic relationships than transitions (i.e., the more rapidly occurring sequence changes). Several amino acids, each with a high likelihood of functionality involving the binding of cytochrome c or interaction with COX VIII, have changed in Anthropoidea, the primate suborder grouping New World monkey, Old World monkey, ape, and human lineages. They are conserved in other mammalian lineages and in nonanthropoid primates. Maximum-likelihood ancestral COX I nucleotide sequences were determined utilizing a near most parsimonious branching arrangement for the primate sequences that was consistent with previously hypothesized primate cladistic relationships based on larger and more diverse data sets. Relative rate tests of COX I mitochondrial sequences showed an elevated nonsynonymous (N) substitution rate for anthropoid–nonanthropoid comparisons. This finding for the largest mitochondrial (mt) DNA-encoded subunit is consistent with previous observations of elevated nonsynonymous substitution/synonymous substitution (S) rates in primates for mt-encoded COX II and for the nuclear-encoded COX IV and COX VIIa-H. Other COX-related proteins, including cytochrome c and cytochrome b, also show elevated amino acid replacement rates or N/S during similar time frames, suggesting that this group of interacting genes is likely to have coevolved during primate evolution.

Ecological and social determinants of birth intervals in baboons

Birth rates in primates have long been proposed to result from an interaction between ecological and social factors. We analyzed a variety of social and environmental variables to determine which ones best explain the observed variation in interbirth intervals across 14 baboon populations. Both the number of females in the group and mean annual temperature were found to be important, and a multivariate equation containing the quadratic components of both these variables accounts for almost all the observed variance in interbirth intervals. The quadratic relationship with temperature is explained in terms of the energetic costs of maintaining a stable body temperature at both low and high temperatures. The quadratic relationship with number of females results from relationships with both food availability and the costs of increasing intragroup competition as group size increases. Although females may be able to exert a certain degree of choice in their reproductive scheduling decisions, they are ultimately constrained by limits imposed upon them by the complex interactions between their ecological and demographic environment.

Unexpectedly similar rates of nucleotide substitution found in male and female hominids.

In 1947, it was suggested that, in humans, the mutation rate is dramatically higher in the male germ line than in the female germ line. This hypothesis has been supported by the observation that, among primates, Y-linked genes evolved more rapidly than homologous X-linked genes. Based on these evolutionary studies, the ratio (alpha(m)) of male to female mutation rates in primates was estimated to be about 5. However, selection could have skewed sequence evolution in introns and exons. In addition, some of the X-Y gene pairs studied lie within chromosomal regions with substantially divergent nucleotide sequences. Here we directly compare human X and Y sequences within a large region with no known genes. Here the two chromosomes are 99% identical, and X-Y divergence began only three or four million years ago, during hominid evolution. In apes, homologous sequences exist only on the X chromosome. We sequenced and compared 38.6 kb of this region from human X, human Y, chimpanzee X and gorilla X chromosomes. We calculated alpha(m) to be 1.7 (95% confidence interval 1.15-2.87), significantly lower than previous estimates in primates. We infer that, in humans and their immediate ancestors, male and female mutation rates were far more similar than previously supposed.

Diversity components of impending primate extinctions.

Many extant species are at risk to go extinct. This impending loss of species is likely to cause changes in future ecosystem functions. Ecological components of diversity, such as dietary or habitat specializations, can be used to estimate the impact of extinctions on ecosystem functions. As an approach to estimate the impact of future extinctions, we tested interdependency between ecological and taxonomic change based on current predictions of extinction rates in primates. We analyzed the ecological characteristics of extant primate faunas having species in various categories of endangerment of extinction and forecasted the future primate faunas as if they were paleontological faunas. Predicting future faunas combines the wealth of ecological information on living primates with large, fossil record-like changes in diversity. Predicted extinction patterns of living primates in Africa, Asia, Madagascar, and South America show that changes in ecology differ among the regions in ways that are not reducible to taxonomic measures. The ecological effects of primate extinctions are initially least severe in South America and larger in Asia and Africa. Disproportionately larger ecological changes are projected for Madagascar. The use of taxonomy as a proxy for ecology can mislead when estimating competence of future primate ecosystems.

Sex Differences in Mutation Rate in Higher Primates Estimated from AMG Intron Sequences

To study sex differences in mutation rate in primates, we sequenced the third introns of the AMGX and AMGY genes from humans, orangutans, and squirrel monkeys and estimated that the male-to-female ratio of mutation rate is alpha = 5.14 with the 95% confidence interval (2.42, 16.6). Combining this data set and the data sets from ZFX/ZFY and SMCX/SMCY introns, we obtained an estimate of alpha = 5.06 with the 95% confidence interval reduced to (3.24, 8.79). The alpha value is significantly higher in higher primates than in rodents.

Measurement of Retinal Blood Velocity and Flow Rate in Primates Using a Liposomedye System

A recently developed liposome-dye method was used to make quantitative measurements of blood velocity and volumetric flow rates in the retina of the rhesus monkey. After systemic injection of a liposome-encapsulated fluorescent dye (calcein), the release of a bolus of the dye in the retina was triggered by an ophthalmic argon laser. Initially, calcein was entrapped at a high concentration and the fluorescence of the dye in the lipid vesicle was quenched. After laser exposure, the liposomes released a bolus of dye at the laser exposure site in a specific vessel of the retina. The released dye formed a well-defined, fluorescent wavefront in the exposed artery or vein. By measuring the distance the dye traveled in the vein over a set time interval, it was possible to measure blood velocity in retinal vessels of various diameters, and to calculate volumetric flow rates in those vessels.

Basal metabolic rates in primates—the possible role of phylogenetic and ecological factors

Basal metabolic rates in primates—the possible role of phylogenetic and ecological factors

Is There a Constant Rate of Molecular Substitution

The current concept of the molecular clock is primarily based on the assumption that there is a constant rate of molecular substitution in all mammals. The calibration of the albumin clock of SARICH & CRONIN (1976) set 100 albumin immunological distance units (IDU) between two taxa equal to a most probable divergence time of 60 m, y. ago, based primarily on the early primate data. On this scale the marsupial-placental albumin immunological distance is about 210 units, corresponding to a period about 125m.y. ago, and the antiquity of the basic placental adaptive radiation is set at 90-100 m.y. ago. These values are will in accord with the paleontological data. According to SARICH & CRONIN, the catarrhine-platyrrhine divergence must have occurred about half as long ago as the beginning of of the prosimian-anthropoid split (70m.y. ago), that is, about 35m. y. ago. The conclusion that the catarrhine-platyrrhine divergence occurred about 35m. y. ago is in concordance with the paleontological records. However, the data of 70m. y. ago for the prosimian-anthropoid split does not agree with the initial assumption of a divergence date of 60m.y. ago given the substitution rate as 0.6m. y. per 1 IDU. Moreover, the paleontological records suggest that their divergence date is 50m.y. ago. These data do not support the assumption that there is a constant rate of molecular substitution. FITCH & LANGLEY (1976) described the relationship between nucleotide substitution and the divergence dates of mammals. The linear relationship between time elapsed and nucleotide substitution is beautifully observed, but all the primate pairs fall significantly below the line. From these results, FITCH & LANGLEY concluded that primates show a lower evolutionary rate of nucleotide substitution. However, they did not show the magnitude of the slowing down of its rate in primates. To correct the observed divergence of the prime data, the primate pairs were re-plotted according to the following method: the numbers for nucleotide substitution of each pair are unchanged, but the paleontologically estimated dates of divergence of each pair are shortened to one-half of the elapsed time estimates used by FITCH & LANGLEY. These new points are beautifully arranged closed to the original correlation line. Most of the new points are still below the line, but the older divergent pair (cercopithecids-pongids) is replotted above the line. This means that the divergence dates predicted by using the cor relation line represent less than half the elapsed time estimated paleontologically, except for the elder divergent pair. This evidence may indicate that the magnitude of the discrepancy between the paleontologically estimated dates and the dates predicted by the molecular clock depends on relative age of divergence among anthropoids: the more recent divergence date, the greater the magnitude of the discrepancy.

Evolution of primate DNA sequences

Abstract This study is concerned with comparing the DNA sequences of different mammals, mainly primates, by utilizing nucleic acid hybridization. Nucleotide sequence differences between different species have been quantitated. Rates of nucleotide sequence change have been calculated. These data suggest that nucleotide sequence change has been decreasing with the development of the primate line. They also indicate that the rate of nucleotide sequence change in Primates is 10 – 20 × lower than that for rodents during recent evolutionary times. When corrected for generation time the rodent and primate rates are essentially equal.