The selective forces acting on amino acid substitutions may be different in the two phases of molecular evolution: polymorphism and fixation. Negative selection and genetic drift may dominate the first phase, whereas positive selection may become much more significant in the second phase. However, the conventional dichotomy of synonymous vs. nonsynonymous changes does not offer the resolution needed to study the dynamics of these two phases. Following previously published methods, we separated amino acid changes into 75 elementary types (1-bp substitution between their respective codons). The likelihood of each type of amino acid change becoming polymorphic (PI, which stands for ''polymorphic index''), relative to synonymous changes, can then be calculated. Similarly, the likelihood of fixation (FI, for "fixation index"), conditional on common polymorphisms, is also calculated. Using Perlegen and HapMap data on human polymorphisms and the chimpanzee sequences as the outgroup, we compared the evolutionary dynamics of the 75 elementary changes in the two phases. We found a strong ''L-shaped'' negative correlation (P < 0.001) between FI and PI. Only those changes with low PIs show FI > 1, which is often a signature of adaptive evolution. These patterns suggest that negative and positive selection operate more effectively on the same set of amino acid changes and that Ϸ10 -13% of amino acid substitutions between humans and chimpanzee may be adaptive. 2). Many studies have attempted to address this issue by considering levels of within-species polymorphism or between-species divergence (3, 4). One may gain further resolution by dividing the process of mutation substitution into two separate phases, polymorphism and fixation. When a new mutation arises in a population, it exists as a low-frequency polymorphism. In this first phase of evolution, the dominant forces are genetic drift and negative selection. If this mutation can reach a substantial frequency (say, 20% in humans), then it is unlikely to be strongly deleterious. Hence, the second phase of evolution, the process of fixation, is governed mainly by drift and positive selection. Whether these two phases are positively or negatively correlated will inform us about how natural selection operates. In this report, we shall address these questions by using human data, but the approach should be general.To investigate the evolutionary dynamics and correlation between these two phases, we need to be able to classify mutations in coding regions into more categories than the traditional nonsynonymous and synonymous dichotomy. We follow the procedure developed by Tang et al. (refs. 5 and 6, see also ref. 7), who classified amino acid changes into 75 elementary types. An elementary amino acid change is one that can be reached by 1-bp substitution in the codons (Phe to Leu, for example). The rest of the 115 types are all composites of two or three elementary changes (Phe to Pro, for example). One can then ask how these 75 elementary changes differ in their likelihoods of ...

Mesoamerica has an important role in the expansion of Paleoamericans as the route to South America. In this study, we determined complete mitogenome sequences of 113 unrelated individuals from two indigenous populations of Mesoamerica, Mazahua and Zapotec. All newly sequenced mitogenomes could be classified into haplogroups A2, B2, C1 and D1, but one sequence in Mazahua was D4h3a, a subclade of haplogroup D4. This haplogroup has been mostly found in South America along the Pacific coast. Haplogroup X2a was not found in either population. Genetic similarity obtained using phylogenetic tree construction and principal component analysis showed that these two populations are distantly related to each other. Actually, the Mazahua and the Zapotec shared no sequences (haplotypes) in common, while each also showed a number of unique subclades. Surprisingly, Zapotec formed a cluster with indigenous populations living in an area from central Mesoamerica to Central America. By contrast, the Mazahua formed a group with indigenous populations living in external areas, including southwestern North America and South America. This intriguing genetic relationship suggests the presence of two paleo-Mesoamerican groups, invoking a scenario in which one group had expanded into South America and the other resided in Mesoamerica.

The Japanese wolf (Canis lupus hodophilax Temminck, 1839) was a subspecies of the gray wolf that inhabited the Japanese Archipelago and became extinct 100-120 years ago. In this study, we determined the whole genomes of nine Japanese wolves from the 19th- early 20th centuries and 11 Japanese dogs and analyzed them along with both modern and ancient wolves and dogs. Genomic analyses indicate that the Japanese wolf was a unique subspecies of the gray wolf that was genetically distinct from both modern and ancient gray wolves, lacking gene flow with other gray wolves. A Phylogenetic tree that minimizes the effects of introgression shows that Japanese wolves are closest to the dog monophyletic group among the gray wolves. Moreover, Japanese wolves show significant genetic affinities with East Eurasian dogs. We estimated the level of introgression from the ancestor of the Japanese wolves to the ancestor of East Eurasian dogs that had occurred in the transitional period from the Pleistocene to the Holocene, at an early stage after divergence from West Eurasian dog lineages. Because of this introgression, Japanese wolf ancestry has been inherited by many dogs through admixture between East Eurasian dog lineages. As a result of this heredity, up to 5.5% of modern dog genomes throughout East Eurasia are derived from Japanese wolf ancestry.

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There have been conflicting arguments as to what happened in the human-chimpanzee speciation event. Patterson et al. (2006, Genetic evidence for complex speciation of humans and chimpanzees. Nature 441:1103-1108) proposed a hypothesis that the human-chimpanzee speciation event involved a complicated demographic process: that is, the ancestral lineages of humans and chimpanzees experienced temporal isolation followed by a hybridization event. This hypothesis stemmed from two major observations: a wide range of human-chimpanzee nucleotide divergence across the autosomal genome and very low divergence in the X chromosome. In contrast, Innan and Watanabe (2006, The effect of gene flow on the coalescent time in the human-chimpanzee ancestral population. Mol Biol Evol. 23:1040-1047) demonstrated that the null model of instantaneous speciation fits the genome-wide divergence data for the two species better than alternative models involving partial isolation and migration. To reconcile these two conflicting reports, we first reexamined the analysis of autosomal data by Patterson et al. (2006). By providing a theoretical framework for their analysis, we demonstrated that their observation is what is theoretically expected under the null model of instantaneous speciation with a large ancestral population. Our analysis indicated that the observed wide range of autosomal divergence is simply due to the coalescent process in the large ancestral population of the two species. To further verify this, we developed a maximum likelihood function to detect evidence of hybridization in genome-wide divergence data. Again, the null model with no hybridization best fits the data. We conclude that the simplest speciation model with instantaneous split adequately describes the human-chimpanzee speciation event, and there is no strong reason to involve complicated factors in explaining the autosomal data.

Fluorescent proteins (FPs) are well known and broadly used as bio-imaging markers in molecular biology research. Many FP genes were cloned from anthozoan species and it was suggested that multi-copies of these genes are present in their genomes. However, the full complement of FP genes in any single coral species remained unidentified. In this study, we analyzed the FP genes in two stony coral species. FP cDNA sequences from Acropora digitifera and Acropora tenuis revealed the presence of a multi-gene family with an unexpectedly large number of genes, separated into short-/middle-wavelength emission (S/MWE), middle-/long-wavelength emission (M/LWE), and chromoprotein (CP) clades. FP gene copy numbers in the genomes of four A. digitifera colonies were estimated as 16–22 in the S/MWE, 3–6 in the M/LWE, and 8–12 in the CP clades, and, in total, 35, 31, 33, and 33 FP gene copies per individual shown by quantitative PCR. To the best of our knowledge, these are the largest sets of FP genes per genome. The fluorescent light produced by recombinant protein products encoded by the newly isolated genes explained the fluorescent range of live A. digitifera, suggesting that the high copy multi-FP gene family generates coral fluorescence. The functionally diverse multi-FP gene family must have existed in the ancestor of Acropora species, as suggested by molecular phylogenetic and evolutionary analyses. The persistence of a diverse function and high copy number multi-FP gene family may indicate the biological importance of diverse fluorescence emission and light absorption in Acropora species.

The vast majority of marine invertebrates spend their larval period as pelagic plankton and are exposed to various environmental cues. Here we investigated the thermotaxis behaviors of the bipinnaria larvae of the starfish, Patiria pectinifera, in association with TRPA ion channels that serve as thermal receptors in various animal species. Using a newly developed thermotaxis assay system, we observed that P. pectinifera larvae displayed positive thermotaxis toward high temperatures, including toward temperatures high enough to cause death. In parallel, we identified two TRPA genes, termed PpTRPA1 and PpTRPA basal, from this species. We examined the phylogenetic position, spatial expression, and channel properties of each PpTRPA. Our results revealed the following: (1) The two genes diverged early in animal evolution; (2) PpTRPA1 and PpTRPA basal are expressed in the ciliary band and posterior digestive tract of the larval body, respectively; and (3) PpTRPA1 is activated by heat stimulation as well as by known TRPA1 agonists. Moreover, knockdown and rescue experiments demonstrated that PpTRPA1 is involved in positive thermotaxis in P. pectinifera larvae. This is the first report to reveal that TRPA1 channels regulate the behavioral response of a marine invertebrate to temperature changes during its planktonic larval period.

Homopolymeric amino acid repeats are tandem repeats of single amino acids. About 650 genes are known to have repeats of this kind comprising seven residues or more in the human genome. According to the evolutionary conservativeness, we classified the repeats into three categories: those whose length is conserved among mammals (CM), those whose length differs among nonprimate mammals but is conserved among primates (CP), and those whose length differs among primates (VP). The frequency of each repeat, especially Ala, Leu, Pro, and Glu repeats, varies greatly in each category. The 3D structure of homopolymeric amino acid repeats is considered to be intrinsically disordered. As expected, a large proportion of the repeats had a disordered structure, and nearly half of the repeats were predicted as completely disordered. However, a number of the repeats predicted to have nondisordered structure: 13% and 25% of the repeats for categories CM and VP, respectively. Comparison of the substitution rates showed a higher Ka/Ks ratio for the genes with not disordered repeats than the genes with disordered repeats. These results indicate that amino acid substitution rates have been elevated in the genes with nondisordered repeats.