Evidence of positive selection acting at the human dopamine receptor D4 gene locus

Associations have been reported of the seven-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene with both attention-deficit/hyperactivity disorder and the personality trait of novelty seeking. This polymorphism occurs in a 48-bp tandem repea

Intra- and interspecific variation of the CCR5 gene in higher primates

We have evaluated the molecular evolution of the chemokine receptor CCR5 in primates. The chemokine receptor CCR5 serves as a major co-receptor for human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection. Knowledge of evolution of the CCR5 molecule and selection on the CCR5 gene may shed light on its functional role. The comparison of differences between intraspecific polymorphisms and interspecific fixed substitutions provides useful information regarding modes of selection during the course of evolution. There is marked polymorphism in the CCR5 gene sequence within different primate species, whereas sequence divergence between different species is small. By using contingency tests, we compared synonymous (SS) and nonsynonymous (NS) CCR5 mutations occurring within and between a broad range of primates. Our results demonstrate that CCR5 evolution did not follow expectations, of strict neutrality at the level of the whole gene. The proportion of NS to SS at the intraspecific level was significantly higher than that observed at the interspecific level. These results suggest that most CCR5 NS polymorphisms are slightly deleterious. However, at domains more closely correlated with its known biological functions, there was no obvious evidence to support deviation from neutrality.

Evolution and biogeography of talpid moles from continental East Asia and the Japanese islands inferred from mitochondrial and nuclear gene sequences

We sequenced the cytochrome b gene from two little-studied mammal species from the highlands of Southwest China, the long-tailed mole Scaptonyx fusicaudus and the gracile shrew-like mole Uropsilus gracilis. This data was used to examine the phylogenetic r

Analysis of 18S rRNA gene of Octostigma sinensis (Projapygoidea : Octostigmatidae) supports the monophyly of Diplura

The phylogenetic position of Diplura within Hexapoda has been controversial. There are three major lineages in Diplura: Campodeoidea, Projapygoidea, and Japygoidea. However, most of the previous studies were restricted to Campodeoidea and Japygoidea. Unti

Phylogeographic analysis of mitochondrial DNA haplogroup F2 in China reveals T12338C in the initiation codon of the NDS gene not to be pathogenic

In this report, we studied on a homoplasmic T12338C change in mitochondrial DNA (mtDNA), which substituted methionine in the translational initiation codon of the NADH dehydrogenase subunit 5 gene (ND5) with threonine. This nucleotide change was originall

Phylogenetic relationships of Drosophila melanogaster species group deduced from spacer regions of histone gene H2A-H2B

Nucleotide sequences of the spacer region of the histone gene H2A-H2B from 36 species of Drosophila melanogaster species group were determined. The phylogenetic trees were reconstructed with maximum parsimony, maximum likelihood, and Bayesian methods by u

Evolution of the DRD2 gene haplotype and its association with alcoholism in Mexican Americans

The human D2 dopamine receptor gene (DRD2) plays a central role in the neuromodulation of appetitive behaviors and is implicated in having a possible role in susceptibility to alcoholism. We genotyped an SNP in DRD2 Exon 8 in 251 nonalcoholic, unrelated, healthy controls and 200 alcoholic Mexican Americans. The DRD2 haplotypes were analyzed using the Exon 8 genotype in combination with five other SNP genotypes, which were obtained from our previous study. The ancestral origins of the DRD2 polymorphisms have been determined by sequencing the homologous region in other higher primates. Twenty DRD2 haplotypes, defined as H1 to H20 based on their frequency from high to low, were obtained in this major minority population. The ancestral haplotype "I-132-G-C-G-A1" and two one-step mutation haplotypes were absent in our study population. The haplotype H1, "I-B1-T-C-A-A1", with the highest frequency in the population, is a three-step mutation from the ancestral form. The first five or eight major haplotypes make up 87% or 95% of the entire population, respectively. The prevalence of the haplotype H1+ (H1/H1 and H1/Hn genotypes) is significantly higher in alcoholics and alcoholic subgroups, including early onset drinkers and benders, than in their respective control groups. The Promoter -141C allele is in linkage disequilibrium (LD) with five other loci in the nonalcoholic group, but not in the alcoholic group. All of the other five loci are in LD in both the alcoholic and control groups. The DRD2 TaqI B allele is in complete LD with the allele located in intron 6. Five SNPs, Promoter -141C, TaqI B (or Intron 6), Exon 7, Exon 8, and TaqI A, are sufficient to define the DRD2 haplotypes in Mexican Americans. Our data indicate that the DRD2 haplotypes are associated with alcoholism in Mexican Americans. (c) 2005 Elsevier Inc. All rights reserved.

Episodic evolution of prolactin receptor gene in mammals: coevolution with its ligand

Divergence of proteins in signaling pathways requires ligand and receptor coevolution to maintain or improve binding affinity and/or specificity. In this paper we show a clear case of coevolution between the prolactin (PRL) gene and its receptor (prolactin receptor, PRLR) in mammals. First we observed episodic evolution of the extracellular and intracellular domains of the PRLR, which is closely consistent with that seen in PRL. Correlated evolution was demonstrated both between PRL and its receptor and between the two domains of the PRLR using Pearson's correlation coefficient. On comparing the ratio of the nonsynonymous substitution rate to synonymous substitution rate (omega=d(N)/d(S)) for each branch of the star phylogeny of mammalian PRLRs, separately for the extracellular domain (ECD) and the transmembrane domain/intracellular domain (TMD/ICD), we observed a lower omega ratio for ECD than TMD/ICD along those branches leading to pig, dog and rabbit but a higher ratio for ECD than TMD/ICD on the branches leading to primates, rodents and ruminants, on which bursts of rapid evolution were observed. These observations can be best explained by coevolution between PRL and its receptor and between the two domains of the PRLR.

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids

The growth hormone (GH) gene family represents an erratic and complex evolutionary pattern, involving many evolutionary events, such as multiple gene duplications, positive selection, the birth-and-death process and gene conversions. In the present study, we cloned and sequenced GH-like genes from three species of New World monkeys (NWM). Phylogenetic analysis strongly suggest monophyly for NWM GH-like genes with respect to those of Old World monkeys (OWM) and hominoids, indicating that independent gene duplications have occurred in NWM GH-like genes. There are three main clusters of genes in putatively functional NWM GH-like genes, according to our gene tree. Comparison of the ratios of nonsynonymous and synonymous substitutions revealed that these three clusters of genes evolved under different kinds of selective pressures. Detailed analysis of the evolution of pseudogenes showed that the evolutionary pattern of this gene family in platyrrhines is in agreement with the so-called birth-and-death process.

Episodic evolution of prolactin gene in primates

In the present study, we obtained exon 2-5 of prolactin (PRL) gene from four primate species by PCR and sequencing. Adding other genes available in GenBank, we calculate amino acid substitution rates for prolactin gene in primate. Comparison of nonsynonymous substitution rate to synonymous substitution rate ratios shows no evidence of positive selection for any lineage of primate prolactin gene. According to this and the facts that (i) no sites under positive selection are inferred by using maximum-likelihood method; (ii) among 32 amino acid replacement that occurred along the rapid evolutionary phase, only two are included in the 40 functionally important residues, indicating that amino acid replacement tends to occur in those functionally unimportant residues; (iii) partial of prolactin function is replaced by placental lactogen in primate at the rapid evolutionary phase of prolactin gene, we thus deem that it is relaxation of purifying selection to some extent rather than positive selection that enforces the rapid evolution of primate prolactin gene.

Composition and evolution of the V2r vorneronasal receptor gene repertoire in mice and rats

Pheromones are chemicals produced and detected by conspecifics to elicit social/sexual physiological and behavioral responses, and they are perceived primarily by the vomeronasal organ (VNO) in terrestrial vertebrates. Two large superfamilies of G protein-coupled receptors, V1rs and V2rs, have been identified as pheromone receptors in vomeronasal sensory neurons. Based on a computational analysis of the mouse and rat genome sequences, we report the first global draft of the V2r gene repertoire, composed of similar to 200 genes and pseudogenes. Rodent V2rs are subject to rapid gene births/deaths and accelerated amino acid substitutions, likely reflecting the species-specific nature of pheromones. Vertebrate V2rs appear to have originated twice prior to the emergence of the VNO in ancestral tetrapods, explaining seemingly inconsistent observations among different V2rs. The identification of the entire V2r repertoire opens the door to genomic-level studies of the structure, function, and evolution of this diverse group of sensory receptors. (c) 2005 Elsevier Inc. All rights reserved.

Molecular evolution of growth hormone gene family in old world monkeys and hominoids

Growth hormone is a classic molecule in the study of the molecular clock hypothesis as it exhibits a relatively constant rate of evolution in most mammalian orders except primates and artiodactyls, where dramatically enhanced rate of evolution (25-50-fold) has been reported. The rapid evolution of primate growth hormone occurred after the divergence of tarsiers and simians, but before the separation of old world monkeys (OWM) from new world monkeys (NWM). Interestingly, this event of rapid sequence evolution coincided with multiple duplications of the growth hormone gene, suggesting gene duplication as a possible cause of the accelerated sequence evolution. Here we determined 21 different GH-like sequences from four species of OWM and hominoids. Combining with published sequences from OWM and hominoids, our analysis demonstrates that multiple gene duplications and several gene conversion events both occurred in the evolutionary history of this gene family in OWM/hominoids. The episode of recent duplications of CSH-like genes in gibbon is accompanied with rapid sequence evolution likely resulting from relaxation of purifying selection. GHN genes in both hominoids and OWM are under strong purifying selection. In contrast, CSH genes in both lineages are probably not. GHV genes in OWM and hominoids evolved at different evolutionary rates and underwent different selective constraints. Our results disclosed the complex history of the primate growth hormone gene family and raised intriguing questions on the consequences of these evolutionary events. © 2005 Elsevier B.V. All rights reserved.

Exclusive gene mapping of congenital microphthalmia in a Chinese family

Congenital microphthalmia is a developmental ocular disorder and might be caused by the mutations in the genes involved in eye development. To uncover the genetic cause in a six-generation Chinese pedigree with autosomal dominant congenital microphthalmia

Haplotype frequency distribution and linkage disequilibrium analysis of single nucleotide polymorphisms at the human FMO3 gene locus

We analyzed flavin-containing monooxygenase 3 (FMO3) polymorphisms, haplotype structure, and linkage disequilibrium (LD) in 256 Han Chinese and 50 African-American individuals to compare their haplotype frequencies and LD with other world populations. For