Present-day Humans Research Articles

Modelling the recent common ancestry of all living humans.

If a common ancestor of all living humans is defined as an individual who is a genealogical ancestor of all present-day people, the most recent common ancestor (MRCA) for a randomly mating population would have lived in the very recent past. However, the random mating model ignores essential aspects of population substructure, such as the tendency of individuals to choose mates from the same social group, and the relative isolation of geographically separated groups. Here we show that recent common ancestors also emerge from two models incorporating substantial population substructure. One model, designed for simplicity and theoretical insight, yields explicit mathematical results through a probabilistic analysis. A more elaborate second model, designed to capture historical population dynamics in a more realistic way, is analysed computationally through Monte Carlo simulations. These analyses suggest that the genealogies of all living humans overlap in remarkable ways in the recent past. In particular, the MRCA of all present-day humans lived just a few thousand years ago in these models. Moreover, among all individuals living more than just a few thousand years earlier than the MRCA, each present-day human has exactly the same set of genealogical ancestors.

Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution.

Humans are genetically deficient in the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc) because of an Alu-mediated inactivating mutation of the gene encoding the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase (CMAH). This mutation occurred after our last common ancestor with bonobos and chimpanzees, and before the origin of present-day humans. Here, we take multiple approaches to estimate the timing of this mutation in relationship to human evolutionary history. First, we have developed a method to extract and identify sialic acids from bones and bony fossils. Two Neanderthal fossils studied had clearly detectable Neu5Ac but no Neu5Gc, indicating that the CMAH mutation predated the common ancestor of humans and the Neanderthal, approximately 0.5-0.6 million years ago (mya). Second, we date the insertion event of the inactivating human-specific sahAluY element that replaced the ancestral AluSq element found adjacent to exon 6 of the CMAH gene in the chimpanzee genome. Assuming Alu source genes based on a phylogenetic tree of human-specific Alu elements, we estimate the sahAluY insertion time at approximately 2.7 mya. Third, we apply molecular clock analysis to chimpanzee and other great ape CMAH genes and the corresponding human pseudogene to estimate an inactivation time of approximately 2.8 mya. Taken together, these studies indicate that the CMAH gene was inactivated shortly before the time when brain expansion began in humankind's ancestry, approximately 2.1-2.2 mya. In this regard, it is of interest that although Neu5Gc is the major sialic acid in most organs of the chimpanzee, its expression is selectively down-regulated in the brain, for as yet unknown reasons.

Reply to comments by Previc: Endocrine differences between humans and great apes—Did environmental factors provide genetic opportunities?

We are very glad to read of Dr. Previc’s enthusiasm for our recent findings on thyroid hormone differences between humans and great apes (Gagneux et al., 2001). We are responding herewith to some of the interesting issues that he has raised. Our paper presented human-ape comparative results on plasma thyroid hormone levels and levels of transthyretin (TTR) in plasma and cerebrospinal fluid (CSF). Given the crucial role of thyroid hormone in brain development, we suggested that developmental studies of humans and great ape thyroid hormone levels are warranted, especially for the CSF/brain side of the blood brain barrier. We did not hypothesize about how such hormonal differences originally came about. Extrapolating from currentday human-ape differences to the series of events that brought about these changes sometime during our evolutionary past is fraught with difficulty. However, we are glad if our results provide potential support to other existing hypotheses. Increased consumption of animal foods and frequent strenuous exercise may indeed have played a crucial role in resetting dopaminergic levels in hominoids, as proposed by Dr. Previc’s extensively researched paper on this subject (Previc, 1999). However, it is also evident that present-day humans can achieve aboveaverage cognitive capacities in the absence of meatrich diets or increased physical activity levels. As far

Primate Evolution of an Olfactory Receptor Cluster: Diversification by Gene Conversion and Recent Emergence of Pseudogenes

The olfactory receptor (OR) subgenome harbors the largest known gene family in mammals, disposed in clusters on numerous chromosomes. We have carried out a comparative evolutionary analysis of the best characterized genomic OR gene cluster, on human chromosome 17p13. Fifteen orthologs from chimpanzee (localized to chromosome 19p15), as well as key OR counterparts from other primates, have been identified and sequenced. Comparison among orthologs and paralogs revealed a multiplicity of gene conversion events, which occurred exclusively within OR subfamilies. These appear to lead to segment shuffling in the odorant binding site, an evolutionary process reminiscent of somatic combinatorial diversification in the immune system. We also demonstrate that the functional mammalian OR repertoire has undergone a rapid decline in the past 10 million years: while for the common ancestor of all great apes an intact OR cluster is inferred, in present-day humans and great apes the cluster includes nearly 40% pseudogenes.

The “Eve” Hypotheses: A Genetic Critique and Reanalysis

Ext d'A.: The simplest hypothesis is that all the mitochondrial DNA (mtDNA) variation found in present-day humans is derived from a single common female ancestor. There is no controversy concerning this hypothesis from a population-genetic perspective. All homologus DNA copies in a population must ultimately be traceable to a common ancestor under the theory of evolution. Since mtDNA is maternally inherited in primates, this implies that all copies of human mitochondrial DNA must trace backward to a common femal ancestor.

Comprehending Kidney Disease

Comprehending Kidney Disease