Common Ancestor Of Mammals Research Articles

Chromosomal Gene Movements Reflect the Recent Origin and Biology of Therian Sex Chromosomes

Mammalian sex chromosomes stem from ancestral autosomes and have substantially differentiated. It was shown that X-linked genes have generated duplicate intronless gene copies (retrogenes) on autosomes due to this differentiation. However, the precise driving forces for this out-of-X gene “movement” and its evolutionary onset are not known. Based on expression analyses of male germ-cell populations, we here substantiate and extend the hypothesis that autosomal retrogenes functionally compensate for the silencing of their X-linked housekeeping parental genes during, but also after, male meiotic sex chromosome inactivation (MSCI). Thus, sexually antagonistic forces have not played a major role for the selective fixation of X-derived gene copies in mammals. Our dating analyses reveal that although retrogenes were produced ever since the common mammalian ancestor, selectively driven retrogene export from the X only started later, on the placental mammal (eutherian) and marsupial (metatherian) lineages, respectively. Together, these observations suggest that chromosome-wide MSCI emerged close to the eutherian–marsupial split approximately 180 million years ago. Given that MSCI probably reflects the spread of the recombination barrier between the X and Y, crucial for their differentiation, our data imply that these chromosomes became more widely differentiated only late in the therian ancestor, well after the divergence of the monotreme lineage. Thus, our study also provides strong independent support for the recent notion that our sex chromosomes emerged, not in the common ancestor of all mammals, but rather in the therian ancestor, and therefore are much younger than previously thought.

Possible involvement of SINEs in mammalian-specific brain formation

Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINEs), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.

Loss of Egg Yolk Genes in Mammals and the Origin of Lactation and Placentation

Embryonic development in nonmammalian vertebrates depends entirely on nutritional reserves that are predominantly derived from vitellogenin proteins and stored in egg yolk. Mammals have evolved new resources, such as lactation and placentation, to nourish their developing and early offspring. However, the evolutionary timing and molecular events associated with this major phenotypic transition are not known. By means of sensitive comparative genomics analyses and evolutionary simulations, we here show that the three ancestral vitellogenin-encoding genes were progressively lost during mammalian evolution (until around 30–70 million years ago, Mya) in all but the egg-laying monotremes, which have retained a functional vitellogenin gene. Our analyses also provide evidence that the major milk resource genes, caseins, which have similar functional properties as vitellogenins, appeared in the common mammalian ancestor ∼200–310 Mya. Together, our data are compatible with the hypothesis that the emergence of lactation in the common mammalian ancestor and the development of placentation in eutherian and marsupial mammals allowed for the gradual loss of yolk-dependent nourishment during mammalian evolution.

Cross-species analysis of the mammalian β-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract

Mammalian beta-defensins are an important family of innate host defense peptides with pleiotropic activities. As a first step to study the evolutionary relationship and biological role of the beta-defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most beta-defensin genes are composed of two exons separated by an intron of variable length, some contain an additional one or two exons encoding an internal pro-sequence, a segment of carboxy-terminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several beta-defensins. Furthermore, all beta-defensin genes are densely clustered in four to five syntenic chromosomal regions, with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of beta-defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some beta-defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, RT-PCR revealed that all but one rat beta-defensin transcript are preferentially expressed in the male reproductive tract, particularly in epididymis and testis, except that Defb4, a human beta-defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most beta-defensins expressed in the reproductive tract are developmentally regulated, with enhanced expression during sexual maturation. Existence of such a vast array of beta-defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.

Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC

CD1 molecules play an important role in the immune system, presenting lipid-containing antigens to T and NKT cells. CD1 genes have long been thought to be as ancient as MHC class I and II genes, based on various arguments, but thus far they have been described only in mammals. Here we describe two CD1 genes in chickens, demonstrating that the CD1 system was present in the last common ancestor of mammals and birds at least 300 million years ago. In phylogenetic analysis, these sequences cluster with CD1 sequences from other species but are not obviously like any particular CD1 isotype. Sequence analysis suggests that the expressed proteins bind hydrophobic molecules and are recycled through intracellular vesicles. RNA expression is strong in lymphoid tissues but weaker to undetectable in some nonlymphoid tissues. Flow cytometry confirms expression from one gene on B cells. Based on Southern blotting and cloning, only two such CD1 genes are detected, located approximately 800 nucleotides apart and in the same transcriptional orientation. The sequence of one gene is nearly identical in six chicken lines. By mapping with a backcross family, this gene could not be separated from the chicken MHC on chromosome 16. Mining the draft chicken genome sequence shows that chicken has only these two CD1 genes located approximately 50 kb from the classical class I genes. The unexpected location of these genes in the chicken MHC suggests the CD1 system was present in the primordial MHC and is thus approximately 600 million years old.

Presence of isochore structures in reptile genomes suggested by the relationship between GC contents of intron regions and those of coding regions.

Vertebrate genomes are mosaics of isochores. On the assumption that marked differences exist in the isochore structure between warm-blooded and cold-blooded animals, variations among vertebrates were previously attributed to adaptation to homeothermy. However, based on the data of coding regions from representatives of extant vertebrates, including a turtle, a crocodile (Archosauromorpha) and a few kinds of snakes (Lepidosauromorpha), it was recently hypothesized that the common ancestors of mammals, birds and extant reptiles already had the "warm-blooded" isochore structure. To test this hypothesis, the nucleotide sequences of alpha-globin genes including non-coding regions (introns) from two snakes, N. kaouthia and E. climacophora, were determined (accession number: AB104824, AB104825). The correlation between the GC contents in the introns and exons of alpha-globin genes from snakes and those from other vertebrates supports the above hypothesis. Similar analysis using data for exons and introns of other genes obtained from the GenBank (Release 131) also support the above hypothesis.

Evolution of Milk Oligosacharides and Lactose.

Living mammals comprise monotremes, marsupials and eutherians (placental mammals). These three Infraclasses, although they differ markedly in their patterns of reproduction, have in common the phenomenon of lactation, i.e. the production of milk by the female subsequent to hatching (monotremes) or birth (marsupials, eutherians).The dominant carbohydrate in the milk of most eutherians is the disaccharide lactose, whose synthesis by the lactating mammary gland is catalysed by lactose synthase, which is a complex consisting of β4galactosyltransferase I and α-lactalbumin. α-Lactalbumin is found only in mammals and is believed to have evolved from lysozyme, an ancient protein which is widely distributed in the animal kingdom. The α-lactalbumin content within the mammary gland is the controlling factor determining the rate of lactose synthesis.The dominant carbohydrates in the milk of monotremes and marsupials and of a few eutherian species are oligosaccharides, i.e. sugars which consist of three or more monosaccharide residues. The milk and colostrum of humans and of some other eutherians also contains significant amounts of oligosaccharides. Milk oligosaccharide synthesis is catalysed by a variety of glycosyltransferases which transfer monosaccharide residues (galactosyl, fucosyl, sialyl or N-acetylglucosaminyl) either to free lactose or to another monosaccharide residue attached to lactose. In terms of chemical structures, eutherian and monotreme oligosaccharides resemble each other whereas the marsupial oligosaccharides are mostly unique, but almost all contain lactose at their reducing ends.Milk oligosaccharides are now recognised as being very significant as anti-microbial compounds against pathogenic microorganisms as well as being an energy source for the young of monotremes and marsupials. Milk oligosaccharides may also provide specific monosaccharides which are required for the postnatal biosynthesis of glycoconjugates, particularly of the nervous system.We propose the following hypothesis for the evolution of milk oligosaccharides. The primitive mammary glands of the first common ancestor of mammals contained lysozyme and a variety of glycosyltransferases but little or no α-lactalbumin. When α-lactalbumin first appeared, its content within the lactating mammary glands was low and lactose was synthesised at a relatively slow rate. Because of the presence of glycosyl transferases, almost all of the lactose was utilised for the synthesis of oligosaccharides and did not accumulate, its steady-state concentration remaining low. Consequently the predominant saccharides in the proto-lacteal secretions or milk produced by this common ancestor were oligosaccharides and not free lactose.Initially, the oligosaccharides served mainly as anti-infection factors against pathogenic organisms. They were then recruited as an energy source for the neonates, and natural selection favoured an increase in their concentration. This was achieved by an increase in the synthesis of α-lactalbumin and possibly also of the glycosyltransferases. The two biological roles of anti-infection and provision of energy were preserved in both monotremes and marsupials but in most eutherians the milk concentration of free lactose increased due to a significant increase in α-lactalbumin synthesis by the mammary gland. Lactose therefore became a significant energy source for most eutherians while oligosaccharides continued to serve mainly as anti-microbial agents. The advent of milk lactose at relatively high concentrations necessitated the prior evolution or co-evolution of brush border small intestinal lactase, which provided an efficient mechanism for the digestion of lactose.

Changes in body temperature pattern in vertebrates do not influence the codon usages of alpha-globin genes.

Codon usages are known to vary among vertebrates chiefly due to variations in isochore structure. Under the assumption that marked differences exist in isochore structure between warm-blooded and cold-blooded animals, the variations among vertebrates were previously attributed to an adaptation to homeothermy. However, based on data from a turtle species and a crocodile (Archosauromorpha), it was recently proposed that the common ancestors of mammals, birds and extent reptiles already had the "warm-blooded" isochore structure. We determined the nucleotide sequences of alpha-globin genes from two species of heterotherms, cuckoo (Cuculus canorus) and bat (Pipistrellus abramus), and three species of snakes (Lepidosauromorpha), Naja kaouthia from a tropical terrestrial habitat, Elaphe climacophora from a temperate terrestrial habitat, and Hydrophis melanocephalus from a tropical marine habitat. Our purposes were to assess the influence of differential body temperature patterns on codon usage and GC content at the third position of a codon (GC3), and to test the hypothesis concerning the phylogenetic position at which GC contents had increased in vertebrates. The results of principal component analysis (PCA) using the present data and data for other taxa from GenBank indicate that the primary difference in codon usage in globin genes among amniotes and other vertebrates lies in GC3. The codon usages (and GC3) in alpha-globin genes from two heterotherms and three snakes are similar to those in alpha-globin genes from warm-blooded vertebrates. These results refute the influence of body temperature pattern upon codon usages (and GC3) in alpha-globin genes, and support the hypothesis that the increase in GC content in the genome occurred in the common ancestor of amniotes.

Histone underacetylation is an ancient component of mammalian X chromosome inactivation.

Underacetylation of histone H4 is thought to be involved in the molecular mechanism of mammalian X chromosome inactivation, which is an important model system for large-scale genetic control in eukaryotes. However, it has not been established whether histone underacetylation plays a critical role in the multistep inactivation pathway. Here we demonstrate differential histone H4 acetylation between the X chromosomes of a female marsupial, Macropus eugenii. Histone underacetylation is the only molecular aspect of X inactivation known to be shared by marsupial and eutherian mammals. Its strong evolutionary conservation implies that, unlike DNA methylation, histone underacetylation was a feature of dosage compensation in a common mammalian ancestor, and is therefore likely to play a central role in X chromosome inactivation in all mammals.

Chromosomal evolution from the perspective of the bovine gene map

Abstract The bovine genome map has grown from a simple synteny map in 1990 to a chromosomal anchored synteny and linkage map today. The current map is a prototypic artiodactyl map which serves as a useful tool for the study of chromosomal evolution. Syntenic conservation is more pronounced in the cattle and human maps than in either of these relative to mouse . The recent development of the bovine linkage map, however, suggests that linear order of genes within conserved syntenic groups is often disparate. The cattle, human, and mouse maps can be used to delineate pathways of chromosomal evolution from a common mammalian ancestor. Conservation of gene order cannot be assumed from conservation of synteny, however, and the establishment of order of comparative anchor loci is essential for future development of cattle and other mammalian maps used for comparative purposes.

Strong conservation of the expression of cystatin C gene in choroid plexus.

The expression of the cystatin C gene was studied by Northern analysis of RNA isolated from the choroid plexus, other brain tissues, and liver from 11 mammalian and 4 avian species. The probe used for hybridization was cystatin C cDNA isolated previously from a rat choroid plexus cDNA library. Strong conservation of the expression of the cystatin C gene in choroid plexus was suggested by the observation of substantial levels of cystatin C mRNA in choroid plexus RNA from all mammalian and avian species studied. In contrast, levels of cystatin C mRNA in total liver RNA varied widely for mammalian as well as for avian species. It was concluded that the synthesis of cystatin C in choroid plexus has probably been conserved since the stage of the stem reptiles, the common ancestors of mammals and birds. The cystatin C gene was also found to be expressed early in ontogeny, as indicated by the observation of similar cystatin C mRNA levels in choroid plexus RNA from newly hatched and adult chickens.