Molecular evolution of microcephalin, a gene determining human brain size

Microcephalin gene is one of the major players in regulating human brain development. It was reported that truncated mutations in this gene can cause primary microcephaly in humans with a brain size comparable with that of early hominids. We studied the m

Molecular evolution of CXCR1, a G protein-coupled receptor involved in signal transduction of neutrophils

Human neutrophils are a type of white blood cell, which forms an early line of defense against bacterial infections. Neutrophils are highly responsive to the chemokine, interleukin-8 (IL-8) due to the abundant distribution of CXCR1, one of the IL-8 receptors on the neutrophil cell surface. As a member of the GPCR family, CXCR1 plays a crucial role in the IL-8 signal transduction pathway in neutrophils. We sequenced the complete coding region of the CXCR1 gene in worldwide human populations and five representative nonhuman primate species. Our results indicate accelerated protein evolution in the human lineage, which was likely caused by Darwinian positive selection. The sliding window analysis and the codon-based neutrality test identified signatures of positive selection at the N-terminal ligand/receptor recognition domain of human CXCR1.

Defining the orientation of the tandem fusions that occurred during the evolution of Indian muntjac chromosomes by BAC mapping

The Indian muntjac (Muntiacus muntjak vaginalis) has a karyotype of 2n=6 in the female and 7 in the male, the karyotypic evolution of which through extensive tandem fusions and several centric fusions has been well-documented by recent molecular cytogenetic studies. In an attempt to define the fusion orientations of conserved chromosomal segments and the molecular mechanisms underlying the tandem fusions, we have constructed a highly redundant (more than six times of whole genome coverage) bacterial artificial chromosome (BAC) library of Indian muntjac. The BAC library contains 124,800 clones with no chromosome bias and has an average insert DNA size of 120 kb. A total of 223 clones have been mapped by fluorescent in situ hybridization onto the chromosomes of both Indian muntjac and Chinese muntjac and a high-resolution comparative map has been established. Our mapping results demonstrate that all tandem fusions that occurred during the evolution of Indian muntjac karyotype from the acrocentric 2n=70 hypothetical ancestral karyotype are centromere-telomere (head-tail) fusions.

Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel Deuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition.

Adaptive evolution of MRGX2, a human sensory neuron specific gene involved in nociception

MRGX2, a G-protein-coupled receptor, is specifically expressed in the sensory neurons of the human peripheral nervous system and involved in nociception. Here, we studied DNA polymorphism patterns and evolution of the MRGX2 gene in world-wide human populations and the representative nonhuman primate species. Our results demonstrated that MRGX2 had undergone adaptive changes in the path of human evolution, which were likely caused by Darwinian positive selection. The patterns of DNA sequence polymorphisms in human populations showed an excess of derived substitutions, which against the expectation of neutral evolution, implying that the adaptive evolution of MRGX2 in humans was a relatively recent event. The reconstructed secondary structure of the human MRGX2 revealed that three of the four human-specific amino acid substitutions were located in the extra-cellular domains. Such critical substitutions may alter the interactions between MRGX2 protein and its ligand, thus, potentially led to adaptive changes of the pain-perception-related nervous system during human evolution. (c) 2005 Elsevier B.V. All rights reserved.

Genetic evidence of a strong functional constraint of neurotrypsin during primate evolution

Neurotrypsin is one of the extra-cellular serine proteases that are predominantly expressed in the brain and involved in neuronal development and function. Mutations in humans are associated with autosomal recessive non-syndromic mental retardation (MR). We studied the molecular evolution of neurotrypsin by sequencing the coding region of neurotrypsin in 11 representative non-human primate species covering great apes, lesser apes, Old World monkeys and New World monkeys. Our results demonstrated a strong functional constraint of neurotrypsin that was caused by strong purifying selection during primate evolution, an implication of an essential functional role of neurotrypsin in primate cognition. Further analysis indicated that the purifying selection was in fact acting on the SRCR domains of neurotrypsin, which mediate the binding activity of neurotrypsin to cell surface or extracellular proteins. In addition, by comparing primates with three other mammalian orders, we demonstrated that the absence of the first copy of the SRCR domain (exon 2 and 3) in mouse and rat was due to the deletion of this segment in the murine lineage. Copyright (C) 2005 S. Karger AG, Basel.

Detecting lineage-specific adaptive evolution of brain-expressed genes in human using rhesus macaque as outgroup

Comparative genetic analysis between human and chimpanzee may detect genetic divergences responsible for human-specific characteristics. Previous studies have identified a series of genes that potentially underwent Darwinian positive selection during huma

No accelerated evolution of 3 ' UTR region in human for brain-expressed genes

The difference in cognitive skills between humans and nonhuman primates is one of the major characters that define our own species. It was previously hypothesized that this divergence might be attributable to genetic differences at gene expression level,

The testis-specific apoptosis related gene TTL.6 underwent adaptive evolution in the lineage leading to humans

The TTL.6 gene is a member of the tubulin-tyrosine ligase (TTL) family involved in apoptosis and preferentially expressed in the testis. We sequenced the coding region and part of the introns of TTL.6 in world wide human populations and five representativ

Rapid evolution, genetic variations, and functional association of the human spermatogenesis-related gene NYD-SP12

NYD-SP12 is a recently identified spermatogenesis-related gene with a pivotal role in human testis development. In this study, we analyzed between-species divergence and within-species variation of NYD-SP12 in seven representative primate species, four wo

Rapid evolution of an X-linked microRNA cluster in primates

MicroRNAs (miRNAs) are a growing class of small RNAs ( about 22 nt) that play crucial regulatory roles in the genome by targeting mRNAs for cleavage or translational repression. Most of the identified miRNAs are highly conserved among species, indicating

Detecting positive darwinian selection in brain-expressed genes during human evolution

To understand the genetic basis that underlies the phenotypic divergence between human and non-human primates, we screened a total of 7176 protein-coding genes expressed in the human brain and compared them with the chimpanzee orthologs to identity genes

Adaptive evolution of SCML1 in primates, a gene involved in male reproduction

Background: Genes involved in male reproduction are often the targets of natural and/or sexual selection. SCML1 is a recently identified X-linked gene with preferential expression in testis. To test whether SCML1 is the target of selection in primates, we