Preferential retention of the slowly evolving gene in pairs of duplicates in angiosperm genomes

Gene duplication provides raw material for functional innovation, but gene duplicability varies considerably. Previous studies have found widespread asymmetrical sequence evolution between paralogs. However, it remains unknown whether the rate of evolution among paralogs affects their propensity of being retained after another round of whole-genome duplication (WGD). In this study, we investigated gene groups that have experienced two successive WGDs to determine which of two older duplicates with different evolutionary rates was more likely to retain both younger duplicates. To uncouple the measurement of evolutionary rates from any assignment of duplicate or singleton status, we measured the evolutionary rates of singleton genes in out-lineages but classified these singleton genes according to whether they are retained or not in a crown group of species. We found that genes that retained younger duplicates in the crown group of genomes were more constrained prior to the younger duplication event than those that failed to leave duplicates. In addition, we also found that the retained clades have more genes in out-lineages. Subsequent analyses showed that genes in the retained clades were expressed more broadly and highly than genes in the singleton clades. We concluded that the set of repeatedly retained genes after two WGDs is biased toward slowly evolving genes in angiosperms, suggesting that the potential of genes for both functional conservation and divergence likely affects their propensity of being retained after WGD in angiosperms.     

VH gene segments in the mouse and human genomes

We have examined the mouse genome sequence to determine its VH gene segment repertoire. In all, 141 segments are mapped to a 3 Mb region of chromosome 12. There is evidence that 92 of these are functional in the mouse strain used for the genome sequence, C57BL/6J; 12 are functional in other mouse strains, and 37 are pseudogenes. The mouse VH gene segment repertoire is therefore twice the size of that in humans. The mouse and human loci bear no large-scale similarity to each other. The 104 functional segments belong to one of the 15 known sequence subgroups, which have been further clustered into eight sets here. Seven of these sets, comprising 101 sequences, are related to five of the human VH families and have the same canonical structures in their hypervariable regions. Duplication of members of one set in the distal half of the locus is mainly responsible for the larger size of the mouse repertoire. Phylogenetic analysis of the VH segments indicates that most of the sequences in the human and mouse VH loci have arisen subsequent to the divergence of the two organisms from their common ancestor.     

A diffusion model for the fate of tandem gene duplicates in diploids

Suppose one chromosome in one member of a population somehow acquires a duplicate copy of the gene, fully linked to the original gene's locus. Preservation is the event that eventually every chromosome in the population is a descendant of the one which initially carried the duplicate. For a haploid population in which the absence of all copies of the gene is lethal, the probability of preservation has recently been estimated via a diffusion approximation. That approximation is shown to carry over to the case of diploids and arbitrary strong selection against the absence of the gene. The techniques used lead to some new results. In the large population limit, it is shown that the relative probability that descendants of a small number of individuals carrying multiple copies of the gene fix in the population is proportional to the number of copies carried. The probability of preservation is approximated when chromosomes carrying two copies of the gene are subject to additional, fully non-functionalizing mutations, thereby modelling either an additional cost of replicating a longer genome, or a partial duplication of the gene. In the latter case the preservation probability depends only on the mutation rate to null for the duplicated portion of the gene.     

Comparative analysis of processed pseudogenes in the mouse and human genomes

Pseudogenes are important resources in evolutionary and comparative genomics because they provide molecular records of the ancient genes that existed in the genome millions of years ago. We have systematically identified approximately 5000 processed pseudogenes in the mouse genome, and estimated that approximately 60% are lineage specific, created after the mouse and human diverged. In both mouse and human genomes, similar types of genes give rise to many processed pseudogenes. These tend to be housekeeping genes, which are highly expressed in the germ line. Ribosomal-protein genes, in particular, form the largest sub-group. The processed pseudogenes in the mouse occur with a distinctly different chromosomal distribution than LINEs or SINEs - preferentially in GC-poor regions. Finally, the age distribution of mouse-processed pseudogenes closely resembles that of LINEs, in contrast to human, where the age distribution closely follows Alus (SINEs).     

Substitution pattern of the CArG element in human and mouse genomes

cis-Elements CArG bound by serum response factor (SRF) are presently being intensively studied, but little is known about the substitution pattern of functional CArG elements. Here, we have performed the first evolutionary analysis of CArGome in the human and mouse genome through bioinformatic methods and statistical tests. We calculated the substitution rate at each site of the functional CArG elements. The results showed that the core sites of the functional CArG elements evolved faster than did the background DNA, indicating that these sites were likely to evolve under positive selection. Moreover, a strong TATA "motif" was evident in the core region within the functional CArG elements in both human and mouse promoters. This motif could probably be a major contribution to the formation of the spatial structure, which was important for CArG-SRF recognition. Thus, the study further revealed the sequence character and substitution pattern of CArG elements and provided useful information for the study of the SRF-binding efficiencies of CArG promoters in functional assays.     

The six hyaluronidase-like genes in the human and mouse genomes.

The human genome contains six hyaluronidase-like genes. Three genes (HYAL1, HYAL2 and HYAL3) are clustered on chromosome 3p21.3, and another two genes (HYAL4 and PH-20/SPAM1) and one expressed pseudogene (HYALP1) are similarly clustered on chromosome 7q31.3. The extensive homology between the different hyaluronidase genes suggests ancient gene duplication, followed by en masse block duplication, events that occurred before the emergence of modern mammals. Very recently we have found that the mouse genome also has six hyaluronidase-like genes that are also grouped into two clusters of three, in regions syntenic with the human genome. Surprisingly, the mouse ortholog of HYALP1 does not contain any mutations, and unlike its human counterpart may actually encode an active enzyme. Hyal-1 is the only hyaluronidase in mammalian plasma and urine, and is also found at high levels in major organs such as liver, kidney, spleen, and heart. A model is proposed suggesting that Hyal-2 and Hyal-1 are the major mammalian hyaluronidases in somatic tissues, and that they act in concert to degrade high molecular weight hyaluronan to the tetrasaccharide. Twenty-kDa hyaluronan fragments are generated at the cell surface in unique endocytic vesicles resulting from digestion by the glycosylphosphatidyl-inositol-anchored Hyal-2, transported intracellularly by an unknown process, and then further digested by Hyal-1. The two beta-exoglycosidases, beta-glucuronidase and beta-N-acetyl glucosaminidase, remove sugars from reducing termini of hyaluronan oligomers, and supplement the hyaluronidases in the catabolism of hyaluronan.     

Density peaks of paralog pairs in human and mouse genomes

Paralog gene trees, which reflect the increase of genomic complexity in the evolution, can be complicated and ambiguous. A simpler complementary approach is analysis of density distribution of paralog pairs. It can reveal general features of genome evolution, which may be hidden in the forest of gene trees. It is known that distribution of human paralog pairs along the axis of protein divergence between pair members forms two main peaks. Here I show that there are three main peaks in the mouse genome. Thus, the multimodality of paralog pair distribution seems to be a fundamental feature of mammalian genomes. Despite the great diversity of domains presented in small amounts or in multidomain architectures with a few predominant domains, both in human and mouse the first peak consists mostly of gene pairs with zinc finger domains or olfactory receptor domain. In the mouse the olfactory receptor predominates, which stipulates the three-peak distribution (since in the olfactory receptors the second peak is closer to the first peak than in other genes). The mammalian-wide zinc finger orthologs are biased towards the second peak. Thus, the marsupial orthologs are nearly absent in the first peak of human and mouse. The gene pairs in the first peak show a lower ratio of nonsynonymous to synonymous substitutions, which suggests that their evolution is more constrained. The plausible explanation is that they are in subfunctionalization state (partition of initial function of ancestral gene), whereas the second peak contains gene pairs that are already in neofunctionalization state (acquiring of novel functions). These data suggest that the adaptive radiation of mammals was accompanied by a burst of duplication of zinc finger genes, which are located in the first (most recent) peak of paralog pairs.     

Origins of new male germ-line functions from X-derived autosomal retrogenes in the mouse

Recent literature demonstrates that retrogenes tend to leave the X chromosome and integrate onto the autosomes and evolve male-biased expression patterns. Several selection-based evolutionary mechanisms have been proposed to explain this observation. Testing these selection-based models requires examining the evolutionary history and functional properties of new retrogenes, particularly those that show evidence of directional movement between the X and the autosomes (X-related retrogenes). This includes autosomal retrogenes with parental paralogs on the X chromosome (X-derived autosomal retrogenes) and those retrogenes integrated onto the X chromosomes (X-linked retrogenes). In order to understand why retrogenes tend to move nonrandomly in genomes, we examined the expression patterns and evolutionary mechanisms concerning gene pairs having young retrogenes--originating less than 20 MYA (after mouse-rat split). We demonstrate that these X-derived autosomal retrogenes evolved a more restricted male-biased expression pattern: they are expressed exclusively or predominantly in the testis, in particular, during the late stages of spermatogenesis. In contrast, the parental counterparts have relatively broad expression patterns in various tissues and spermatogenetic stages. We further observed that positive selection is targeting these X-derived autosomal retrogenes with novel male-biased expression patterns. This suggests that such retrogenes evolved new male germ-line functions that may be complementary to the functions of the parental paralogs, which themselves contribute little during spermatogenesis. Such evolutionary changes may be beneficial to the populations. Furthermore, most identified X-related retrogenes have recruited novel adjacent sequences as their untranslated regions (UTRs), suggesting that these UTRs, acquired de novo, may play an important role in establishing new regulatory mechanisms to carry out the new male germ-line functions.     

An analysis on gene architecture in human and mouse genomes

A comparative genome analysis on exon-intron distribution profiles is performed for human and mouse genomes to deduce similarities and differences between them. Interestingly, both in human and mouse genomes, the total length in introns and intergenic DNA on each chromosome is significantly correlated to the chromosome size. The results presented provide a framework for understanding the nature and patterns of exon-intron length distributions, the constraints on them and their role in genome design and evolution.     

Selective constraint in intergenic regions of human and mouse genomes.

We aligned and analyzed 100 pairs of complete, orthologous intergenic regions from the human and mouse genomes (average length approximately 12 000 nucleotides). The alignments alternate between highly similar segments and dissimilar segments, indicating a wide variation of selective constraint. The average number of selectively constrained nucleotides within a mammalian intergenic region is at least 2000. This is threefold higher than within a nematode intergenic region and at least twofold higher than the number of selectively constrained nucleotides coding for an average protein. Because mammals possess only two- to threefold more proteins than Caenorhabditis elegans, the higher complexity of mammals might be primarily because of the functioning of intergenic DNA.     

The scattered distribution of actin genes in the mouse and human genomes.

A hamster actin cDNA probe was used to localize actin genes on the major components of mouse and human DNAs, namely on the four families of fragments forming the bulk of these genomes. Over 20 EcoRI fragments hybridizing the probe could be detected; a different subset of these fragments was found in each component. Since the fragment families forming the major components of the mouse and human DNAs derive from very long chromosomal segments, the isochores , the presence of actin genes on all components provides evidence for their dispersion in both genomes. In situ hybridization of 125I-labeled probe to metaphase chromosomes in the presence of dextran sulfate confirmed this dispersion by showing that the 29-30 actin gene sites so identified are distributed on almost all chromosomes. Moreover, some human actin genes could be mapped on specific chromosomal segments; in particular, one gene was localized on the long arm of the X chromosome. Finally, three different mouse actin genes were isolated from a recombinant DNA library and previously investigated interspersed repeated sequences were identified in the vicinity of these genes.     

Computational comparison of two mouse draft genomes and the human golden path

Background  

The availability of both mouse and human draft genomes has marked the beginning of a new era of comparative mammalian genomics. The two available mouse genome assemblies, from the public mouse genome sequencing consortium and Celera Genomics, were obtained using different clone libraries and different assembly methods.     

Quantifying the major mechanisms of recent gene duplications in the human and mouse genomes: a novel strategy to estimate gene duplication rates

Background  

The rate of gene duplication is an important parameter in the study of evolution, but the influence of gene conversion and technical problems have confounded previous attempts to provide a satisfying estimate. We propose a new strategy to estimate the rate that involves separate quantification of the rates of two different mechanisms of gene duplication and subsequent combination of the two rates, based on their respective contributions to the overall gene duplication rate.     

Importance of lineage-specific expansion of plant tandem duplicates in the adaptive response to environmental stimuli

Plants have substantially higher gene duplication rates compared with most other eukaryotes. These plant gene duplicates are mostly derived from whole genome and/or tandem duplications. Earlier studies have shown that a large number of duplicate genes are retained over a long evolutionary time, and there is a clear functional bias in retention. However, the influence of duplication mechanism, particularly tandem duplication, on duplicate retention has not been thoroughly investigated. We have defined orthologous groups (OGs) between Arabidopsis (Arabidopsis thaliana) and three other land plants to examine the functional bias of retained duplicate genes during vascular plant evolution. Based on analysis of Gene Ontology categories, it is clear that genes in OGs that expanded via tandem duplication tend to be involved in responses to environmental stimuli, while those that expanded via nontandem mechanisms tend to have intracellular regulatory roles. Using Arabidopsis stress expression data, we further demonstrated that tandem duplicates in expanded OGs are significantly enriched in genes that are up-regulated by biotic stress conditions. In addition, tandem duplication of genes in an OG tends to be highly asymmetric. That is, expansion of OGs with tandem genes in one organismal lineage tends to be coupled with losses in the other. This is consistent with the notion that these tandem genes have experienced lineage-specific selection. In contrast, OGs with genes duplicated via nontandem mechanisms tend to experience convergent expansion, in which similar numbers of genes are gained in parallel. Our study demonstrates that the expansion of gene families and the retention of duplicates in plants exhibit substantial functional biases that are strongly influenced by the mechanism of duplication. In particular, genes involved in stress responses have an elevated probability of retention in a single-lineage fashion following tandem duplication, suggesting that these tandem duplicates are likely important for adaptive evolution to rapidly changing environments.