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The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗

Structural analysis of the unique insecticidal activity of novel mungbean defensin VrD1 reveals possibility of homoplasy evolution between plant defensins and scorpion neurotoxins.

A variety of evolutionarily related defensin molecules is found in plants and animals. Plant gamma-thionins and scorpion neurotoxins, for instance, may be categorized in this functional group, although each class recognizes a distinct receptor binding site. Such molecules are also categorized into the superfamily of cysteine-rich proteins. Plant defensins were generally believed to be involved in antimicrobial or antifungal mechanisms and, unlike scorpion toxins, little is known about whether these molecules are also endowed with the function of insect resistance. We have previously reported the isolation of a cDNA encoding a small cysteine-rich protein designated VrD1 (VrCRP) from a bruchid-resistant mungbean, which is apparently the first discovered plant defensin exhibiting in vitro and in vivo both insecticidal and antifungal activities. Our previous data also successfully demonstrated that VrD1 is toxic to E. coli and able to completely arrest the growth of Sf-21 insect cells at low concentration. However, the molecular and structural basis of this unique insecticidal activity of VrD1 is not clear. Therefore, in the present study, we use structural approach and phylogenic analysis to investigate the evolutionary and functional relations for such unique insecticidal activity. From our results, it is suggested that VrD1, in addition to gamma-thionins and several amylase inhibitors, is highly homologous to scorpion toxins, especially the short toxins. Moreover, based on the observation from our homology structures, VrD1 may utilize a newly found cluster of basic residues to achieve its insecticidal function, whereas all the other plant gamma-thionins were known to use a previously identified basic cluster conserved for gamma-thionins. Considering the general feature of short scorpion toxins to act on insect cell membranes with K(+)- or Cl(-)-channels as molecular targets, our analysis of interaction and recognition modes provides reasonable correlations between this newly found basic cluster and the insecticidal activity of VrD1, which is also comprehended as a possible link for "homoplasy evolution" between plant and animal defensin molecules.

Amino Acid Sequence↗

The evolutionary history of chromosomal super-integrons provides an ancestry for multiresistant integrons.

Integrons are genetic elements that acquire and exchange exogenous DNA, known as gene cassettes, by a site-specific recombination mechanism. Characterized gene cassettes consist of a target recombination sequence (attC site) usually associated with a single open reading frame coding for an antibiotic resistance determinant. The affiliation of multiresistant integrons (MRIs), which contain various combinations of antibiotic resistance gene cassettes, with transferable elements underlies the rapid evolution of multidrug resistance among diverse Gram-negative bacteria. Yet the origin of MRIs remains unknown. Recently, a chromosomal super-integron (SI) harboring hundreds of cassettes was identified in the Vibrio cholerae genome. Here, we demonstrate that the activity of its associated integrase is identical to that of the MRI integrase, IntI1. We have also identified equivalent integron superstructures in nine distinct genera throughout the gamma-proteobacterial radiation. Phylogenetic analysis revealed that the evolutionary history of the system paralleled that of the radiation, indicating that integrons are ancient structures. The attC sites of the 63 antibiotic-resistance gene cassettes identified thus far in MRIs are highly variable. Strikingly, one-fifth of these were virtually identical to the highly related yet species-specific attC sites of the SIs described here. Furthermore, antimicrobial resistance homologues were identified among the thousands of genes entrapped by these SIs. Because the gene cassettes of SIs are substrates for MRIs, these data identify SIs as the source of contemporary MRIs and their cassettes. However, our demonstration of the metabolic functions, beyond antibiotic resistance and virulence, of three distinct SI gene cassettes indicates that integrons function as a general gene-capture system for bacterial innovation.

Alteromonas↗

Structural stabilization of GTP-binding domains in circularly permuted GTPases: implications for RNA binding.

GTP hydrolysis by GTPases requires crucial residues embedded in a conserved G-domain as sequence motifs G1-G5. However, in some of the recently identified GTPases, the motif order is circularly permuted. All possible circular permutations were identified after artificially permuting the classical GTPases and subjecting them to profile Hidden Markov Model searches. This revealed G4-G5-G1-G2-G3 as the only possible circular permutation that can exist in nature. It was also possible to recognize a structural rationale for the absence of other permutations, which either destabilize the invariant GTPase fold or disrupt regions that provide critical residues for GTP binding and hydrolysis, such as Switch-I and Switch-II. The circular permutation relocates Switch-II to the C-terminus and leaves it unfastened, thus affecting GTP binding and hydrolysis. Stabilizing this region would require the presence of an additional domain following Switch-II. Circularly permuted GTPases (cpGTPases) conform to such a requirement and always possess an 'anchoring' C-terminal domain. There are four sub-families of cpGTPases, of which three possess an additional domain N-terminal to the G-domain. The biochemical function of these domains, based on available experimental reports and domain recognition analysis carried out here, are suggestive of RNA binding. The features that dictate RNA binding are unique to each subfamily. It is possible that RNA-binding modulates GTP binding or vice versa. In addition, phylogenetic analysis indicates a closer evolutionary relationship between cpGTPases and a set of universally conserved bacterial GTPases that bind the ribosome. It appears that cpGTPases are RNA-binding proteins possessing a means to relate GTP binding to RNA binding.

Amino Acid Sequence↗

Towards unbiased parentage assignment: combining genetic, behavioural and spatial data in a Bayesian framework.

Inferring the parentage of a sample of individuals is often a prerequisite for many types of analysis in molecular ecology, evolutionary biology and quantitative genetics. In all but a few cases, the method of parentage assignment is divorced from the methods used to estimate the parameters of primary interest, such as mate choice or heritability. Here we present a Bayesian approach that simultaneously estimates the parentage of a sample of individuals and a wide range of population-level parameters in which we are interested. We show that joint estimation of parentage and population-level parameters increases the power of parentage assignment, reduces bias in parameter estimation, and accurately evaluates uncertainty in both. We illustrate the method by analysing a number of simulated test data sets, and through a re-analysis of parentage in the Seychelles warbler, Acrocephalus sechellensis. A combination of behavioural, spatial and genetic data are used in the analyses and, importantly, the method does not require strong prior information about the relationship between nongenetic data and parentage.

Animals↗

Evolution of enterovirus 70 in nature: all isolates were recently derived from a common ancestor.

The data of large RNase T1-resistant oligonucleotide mapping of enterovirus 70 (EV 70) previously reported (Takeda et al., Virology 134, 375-388, 1984) were subjected to further genetical analysis to estimate the evolutionary rate of genome RNA of EV 70 and to clarify the phylogenetic relationship among isolates. A proportion of common spots between strains decreased as the year elapsed and eventually, only seven spots were common to all the 16 isolates tested, indicating that the substitution is scattered throughout the genome. On the other hand, some specific sets of spots were conserved among geographically or epidemiologically related strains. Base sequence variation of the isolates was deduced according to Aaronson et al. (Nucleic Acids Res. 10, 237-246, 1982) from pariwise comparison of the common spots and used as a genetic distance between them. The base substitution rate of virus genome was estimated by regression analysis of the genetic distance of the isolates against the sampling time. A fairly constant and rapid rate was obtained; it was 1.83 X 10(-3)/base/year. Based on the substitution rate, genetic distance and sampling time of the strains, the phylogenetic tree of EV 70 was constructed using Unweighted Pair Group Method Using Arithmetic Averages (UPGMA) (Nei, Molecular Population Genetics and Evolution, North Holland, Amsterdam, 1975). The tree supports the previous hypothesis that evolution of EV 70 started from a single common ancestor. The time of its emergence was estimated to be 1967 +/- 15 months. The virus branched into many strains early during the first pandemic and has evolved in a divergent fashion, yielding genetically polymorphic viruses in the world.

Biological Evolution↗

Genetic and functional analysis of the von Hippel-Lindau (VHL) tumour suppressor gene promoter.

The VHL gatekeeper tumour suppressor gene is inactivated in the familial cancer syndrome von Hippel-Lindau disease and in most sporadic clear cell renal cell carcinomas. Recently the VHL gene product has been identified as a specific component of a SCF-like complex, which regulates proteolytic degradation of the hypoxia inducible transcription factors HIF-1 and HIF-2. pVHL is critical for normal development and mRNA expression studies suggest a role in nephrogenesis. Despite the importance of VHL in oncogenesis and development, little is known about the regulation of VHL expression. To investigate VHL promoter activity, we performed comparative sequence analysis of human, primate, and rodent 5' VHL sequences. We then proceeded to deletion analysis of regions showing significant evolutionary conservation between human and rat promoter sequences, and defined two positive and one negative regulatory regions. Analysis of specific putative transcription factor binding sites identified a functional Sp1 site, which was shown to be a regulatory element. Overlapping Sp1/AP2 sites were also identified and candidate E2F1 binding sites evaluated. Three binding sites for as yet unidentified transcription factors were mapped also. These investigations provide a basis for elucidating the regulation of VHL expression in development, the molecular pathology of epigenetic silencing of VHL in tumourigenesis, and suggest a possible link between Sp1, VHL, and nephrogenesis.

Animals↗

In silico identification and Bayesian phylogenetic analysis of multiple new mammalian kallikrein gene families.

Kallikrein gene families have been identified previously in genomes of the human, the mouse, and the rat, and individual kallikrein-like genes have been found in many more species. This study presents the in silico identification of kallikrein gene families in the recently sequenced genomes of four additional mammalian species, the chimpanzee, the dog, the pig, and the opossum. Phylogenies were constructed with gene sequences from all seven mammalian families, using Bayesian analysis, which clarified the evolutionary relationships between these genes. Individual gene sequences, as well as concatenated constructs of multiple sequences, were used. Fifteen kallikrein genes were located in the chimpanzee (Pan troglodytes) genome, while only 14 were identified in the canine (Canis familiaris) genome as no orthologue to human KLK3 was found. Thirteen genes were identified from the pig (Sus scrofa) genome, which lacked homologues to KLK2 and KLK3, and 11 genes, orthologous to human KLK5 through KLK15, were found in the opossum (Monodelphis domestica) genome. No kallikrein genes were identified from the available genome sequences of the chicken (Gallus gallus) or African clawed frog (Xenopus tropicalis). Within the family of kallikreins several subfamilies were suggested by phylogenetic analysis. One consisted of KLK4, KLK5, and KLK14; another of KLK9, KLK11, and KLK15; a third of KLK10 and KLK12; a fourth of KLK6 and KLK13; and finally one of KLK8 and the classical kallikreins (KLK1, KLK2, and KLK3).

Animals↗

Bayesian models of episodic evolution support a late precambrian explosive diversification of the Metazoa.

Multicellular animals, or Metazoa, appear in the fossil records between 575 and 509 million years ago (MYA). At odds with paleontological evidence, molecular estimates of basal metazoan divergences have been consistently older than 700 MYA. However, those date estimates were based on the molecular clock hypothesis, which is almost always violated. To relax this hypothesis, we have implemented a Bayesian approach to describe the change of evolutionary rate over time. Analysis of 22 genes from the nuclear and the mitochondrial genomes under the molecular clock assumption produced old date estimates, similar to those from previous studies. However, by allowing rates to vary in time and by taking small species-sampling fractions into account, we obtained much younger estimates, broadly consistent with the fossil records. In particular, the date of protostome-deuterostome divergence was on average 582 +/- 112 MYA. These results were found to be robust to specification of the model of rate change. The clock assumption thus had a dramatic effect on date estimation. However, our results appeared sensitive to the prior model of cladogenesis, although the oldest estimates (791 +/- 246 MYA) were obtained under a suboptimal model. Bayes posterior estimates of evolutionary rates indicated at least one major burst of molecular evolution at the end of the Precambrian when protostomes and deuterostomes diverged. We stress the importance of assumptions about rates on date estimation and suggest that the large discrepancies between the molecular and fossil dates of metazoan divergences might partly be due to biases in molecular date estimation.

Algorithms↗

Functional analysis of the small subunit of the putative homoaconitase from Pyrococcus horikoshii in the Thermus lysine biosynthetic pathway.

An in vivo disruption-integration vector system for Thermus thermophilus was developed and used for the functional analysis of an evolutionary-related archaeal protein for lysine biosynthesis. In contrast to fungal one, the putative homoaconitase of T. thermophilus consists of two subunits and catalyzes the second and third steps of lysine biosynthesis. ORFs from hyperthermophilic archaeon Pyrococcus horikoshii, PH1726 and PH1724, share a high degree of amino acid identity with the T. thermophilus subunits LysT and LysU, respectively. In the present report, gene encoding the putative small subunit of archaeal homoaconitase, PH1724, was integrated into the lysU locus of T. thermophilus. The archaeal gene was expressed under the control of PslpA promoter and functional analyses were performed. Transformants were able to grow on minimal medium without lysine when PH1724 ORF was integrated, whereas the lysU disruption led to lysine auxotrophy. Chromosomal integration was verified by PCR analysis, and homoaconitase assay showed that the archaeal gene product functions as a small subunit of homoaconitase, possibly by forming a heterodimer with the LysT subunit of T. thermophilus. These results strongly suggest the functional relation of P. horikoshii PH1724 with LysU in the Thermus lysine biosynthetic pathway, together with functional assignment of LysU as small subunit of homoaconitase. In addition, the provided results indicate that archaeal genes products from hyperthermophiles can be studied in a thermophilic eubacterium such as T. thermophilus.

Amino Acid Sequence↗

Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the beta subunit.

Human alcohol dehydrogenase (ADH) exists as a heterogeneous group of isozymes capable of oxidizing a wide variety of aliphatic and aromatic alcohols. The five distinct human ADH subunits, each encoded by a separate gene, are differentially expressed during development and are subject to tissue-specific regulation. To analyze the organization and regulation of human ADH genes we first isolated a cDNA clone (pADH12) encoding the 3' portion of the beta ADH gene. In the current study pADH12 was used to screen a human genomic library, and several overlapping and nonoverlapping clones were selected. Hybridization and partial nucleotide sequence analyses of the clones indicated that three full-length human ADH genes encoding the alpha, beta, and gamma subunits were isolated. Human genomic DNA hybridization results indicate that the alpha, beta, and gamma ADH genes form a closely related gene family and suggest that the other known human ADH genes (i.e. those encoding the pi and chi subunits) share a more distant evolutionary relationship. Nucleotide sequence analysis of the beta ADH gene reveals that the coding region is interrupted by eight introns and spans approximately 15 kilobases. A presumptive transcription initiation site for the beta ADH gene was located by S1 nuclease mapping at a position 70 base pairs upstream of the start codon. The 5' flanking region possesses a TATA box promoter element as well as two tandem DNA sequences which display homology to previously examined glucocorticoid-responsive elements.

Alcohol Dehydrogenase↗

Evolutionary relationships among proteins probed by an iterative neighborhood cluster analysis (INCA). Alignment of bacteriorhodopsins with the yeast sequence YRO2.

PURPOSE: Searching the existing databases for homologous sequences is essential to understanding a protein's structure and function. For a query sequence, its nearest neighbors can be identified by BLAST (basic local alignment search tool). However, a single query sequence is sufficient to define the entire neighborhood of related sequences, and multiple BLAST queries are needed. We describe here a program which permits automated and iterative BLAST analysis of an entire neighborhood of sequences and apply this to search for homologs of the bacteriorhodopsins outside the archaea phylum. METHODS: We have developed a Java program, 'Iterative Neighborhood Cluster Analysis' (INCA), which performs iterative BLAST searches, beginning with a single starter sequence, and proceeding with any other sequence achieving a predefined minimum alignment score. This results in a cluster of sequences where each sequence is related to at least one other sequence by the cutoff score, additional lists of more distantly related sequences for each member of cluster. RESULTS: Bacteriorhodopsins had not been previously aligned with any other protein family with scores indicative of probable homology. Using INCA, we identified a probable homolog in yeast, YRO2_YEAST, also containing seven putative transmembrane domains. A finding of probable homology was supported by additional alignment strategies. CONCLUSIONS: INCA is a useful tool to assess complete protein neighborhoods. With an increasing database, INCA can serve to detect the emergence of evolutionary links between even the most distantly related protein families. Identifying a homolog of the bacteriorhodopsins in yeast illustrates this approach but at the same time highlights the vast evolutionary distances between polytopic membrane proteins, such as the bacteriorhodopsins.

Amino Acid Sequence↗

[Phylogeographic approach in the interpretation of mitochondrial DNA sequencing results in forensics].

In recent years, forensic mitochondrial DNA analysis has been undertaken from an evolutionary perspective. In particular, the phylogeographic approach based on a phylogenetic analysis of the spatial distribution of mitochondrial haplotypes and haplogroups appears to be a useful tool in the interpretation of identification cases. In this study, the phylogeographic approach has been employed in the analysis of three difficult forensic cases, where single nucleotide, homoplasmic differences were found between the reference and evidentiary haplotypes. mtDNA sequence variation has been examined by the control region (HVS I and HVS II) direct sequencing. Additionally, in order to clarify the subhaplogroup status of the selected haplotypes, DNA sequences of entire mitochondrial genomes obtained from two samples representing J1b subclade have been analyzed.

DNA Fingerprinting↗

A genome-wide survey of R gene polymorphisms in Arabidopsis.

We used polymorphism analysis to study the evolutionary dynamics of 27 disease resistance (R) genes by resequencing the leucine-rich repeat (LRR) region in 96 Arabidopsis thaliana accessions. We compared single nucleotide polymorphisms (SNPs) in these R genes to an empirical distribution of SNP in the same sample based on 876 fragments selected to sample the entire genome. LRR regions are highly polymorphic for protein variants but not for synonymous changes, suggesting that they generate many alleles maintained for short time periods. Recombination is also relatively common and important for generating protein variants. Although none of the genes is nearly as polymorphic as RPP13, a locus previously shown to have strong signatures of balancing selection, seven genes show weaker indications of balancing selection. Five R genes are relatively invariant, indicating young alleles, but all contain segregating protein variants. Polymorphism analysis in neighboring fragments yielded inconclusive evidence for recent selective sweeps at these loci. In addition, few alleles are candidates for rapid increases in frequency expected under directional selection. Haplotype sharing analysis revealed significant underrepresentation of R gene alleles with extended haplotypes compared with 1102 random genomic fragments. Lack of convincing evidence for directional selection or selective sweeps argues against an arms race driving R gene evolution. Instead, the data support transient or frequency-dependent selection maintaining protein variants at a locus for variable time periods.

Arabidopsis↗

Analyzing developmental sequences within a phylogenetic framework.

Heterochrony is important as a potential mechanism of evolutionary change. However, the analysis of developmental timing data within a phylogenetic framework to identify important shifts has proven difficult. In particular, analytical problems with sequence (event) heterochrony revolve around the lack of an absolute time frame in development to allow standardization of timing data across species. An important breakthrough in this regard is the method of "event-pairing," which compares the relative timing of developmental events in a pairwise fashion. The resulting event-pair-encoded data can be mapped onto a phylogeny, which can provide important biological information. However, event-paired data are cumbersome to work with and lack a rigorous quantitative framework under which to analyze them. Critically, the otherwise advantageous relativity of event-pairing prevents an assessment of whether one or both events in a single event-pair have changed position during evolutionary history. Building on the method of event-pairing, we describe a protocol whereby event-pair transformations along a given branch are analyzed en bloc. Our method of "event-pair cracking" thereby allows developmental timing data to be analyzed quantitatively within a phylogenetic framework to infer key heterochronic shifts. We demonstrate the utility of event-pair cracking through a worked example and show how it provides a set of desired features identified by previous authors.

Animals↗

Molecular analysis of Cotton leaf curl virus-Sudan reveals an evolutionary history of recombination.

Monopartite begomoviral DNAs (2761 bp) were cloned and sequenced from field cotton, okra, and Sida alba, from Gezira, and field okra from Shambat. Comparison of the four apparent full-length begomoviral DNAs revealed 99.3-99.5% shared nucleotide (nt) identity, indicating that they are the same viral species, hereafter, referred to as Cotton leaf curl virus-Sudan (CLCuV-SD). Host range studies revealed that the field okra isolate of CLCuV-SD was whitefly-transmissible from okra to okra, M. parviflora, and hollyhock, but not to cotton. In contrast, the cotton isolate of CLCuV-SD infected cotton and hollyhock, but not okra. The genome of CLCuV-SD encodes six open reading frames (ORFs), and was most closely related to other monopartite begomoviruses of the Eastern Hemisphere. CLCuV-SD shared highest nucleotide sequence identity (95.5%) with Okra enation virus (OkEV), but was distantly related (approximately 74% nt sequence identity) to begomoviruses isolated from cotton in Pakistan. While extensive genomic regions of CLCuV-SD and OkEV are highly conserved (approximately 99% nt identity), nt sequence identity of the V1 ORF encoding the coat protein was uncharacteristically low (87.9%), suggesting a history of recombination. An analysis conducted with Sawyer's GENECONV program support the recombination hypothesis, indicating that the V1 ORF and a small segment of the intergenic region of CLCuV-SD and OkEV were derived from other begomoviruses. As a BLAST analysis failed to identify a prospective extant source of either V1 ORF, the parental viruses serving as CP donors remain undiscovered or are extinct.

Evolution, Molecular↗

Genome variation and evolution of the malaria parasite Plasmodium falciparum.

Infections with the malaria parasite Plasmodium falciparum result in more than 1 million deaths each year worldwide. Deciphering the evolutionary history and genetic variation of P. falciparum is critical for understanding the evolution of drug resistance, identifying potential vaccine candidates and appreciating the effect of parasite variation on prevalence and severity of malaria in humans. Most studies of natural variation in P. falciparum have been either in depth over small genomic regions (up to the size of a small chromosome) or genome wide but only at low resolution. In an effort to complement these studies with genome-wide data, we undertook shotgun sequencing of a Ghanaian clinical isolate (with fivefold coverage), the IT laboratory isolate (with onefold coverage) and the chimpanzee parasite P. reichenowi (with twofold coverage). We compared these sequences with the fully sequenced P. falciparum 3D7 isolate genome. We describe the most salient features of P. falciparum polymorphism and adaptive evolution with relation to gene function, transcript and protein expression and cellular localization. This analysis uncovers the primary evolutionary changes that have occurred since the P. falciparum-P. reichenowi speciation and changes that are occurring within P. falciparum.

Animals↗

From The Cover: Binocularity and brain evolution in primates.

Primates are distinguished by frontally directed, highly convergent orbits, which are associated with stereoscopic vision. Although stereoscopic vision requires specialized neural mechanisms, its implications for brain evolution are unknown. Using phylogenetic comparative analysis, I show that evolutionary increases among primate taxa in the degree of orbital convergence correlate with expansion of visual brain structures and, as a consequence, with the overall size of the brain. This pattern is found across the whole primate order and is also repeated within each of the two major primate subtaxa. The visual expansion associated with increased binocularity is specific to the parvocellular visual pathway, consistent with recent evidence implicating this pathway in fine-grained stereopsis. The results support the hypothesis that brain size evolution in primates was associated with visual specialization.

Animals↗