Human evolution and the Y chromosome

The past two years have seen the increased study of Y-chromosome polymorphisms and their relationship to human evolution and variation. Low Y-chromosome sequence diversity indicates that the common ancestor of all extant Y chromosomes lived relatively recently and the consensus of estimates of time to the most recent common ancestor concur with estimates of the mitochondrial DNA ancestor; but we do not know where this ‘Adam’ lived. Though the reason for low nucleotide diversity on the Y-chromosome remains unresolved, some of the mutations are proving highly informative in tracing human prehistoric migrations and are generating new hypotheses on human colonizations and migrations. The recent discovery of highly polymorphic microsatellites on the Y offers new possibilities for the investigation of more recent human evolutionary events, including the identification of male founders.     

Origin and evolution of the Drosophila Y chromosome

Three recent findings are making a deep impact on our understanding of the Drosophila Y. First, the sequencing of the Drosophila genome and the development of proper computational methods increased the number of known single-copy Y-linked genes from 1 to 16, and revealed a chromosome packed with genes acquired from the autosomes. Second, this, coupled with the finding that B-chromosomes are able to show very regular segregation from the X chromosome, reinforce the hypothesis that the Drosophila Y is a specialized B-chromosome, instead of a degenerated homologue of the X. Third and finally, Y chromosomes seem to have a strong effect on male fitness.     

人类Y染色体的演化

人类Y染色体由于其性别决定的特殊功能和独有的进化史一直以来都备受关注。Y染色体起源于常染色体,经历了严重的退化过程。由于其缺乏重组,蛋白编码基因少,重复序列多所以研究进展缓慢。近年来,随着比较基因组及测序技术的快速发展,对人类Y染色体最终命运的争论不断加剧,Y染色体的研究正逐步成为热点。文章综述了人类Y染色体的结构、遗传特点、起源及进化过程,并根据目前的研究进展对Y染色体的最终命运进行了讨论,提出了作者的一些看法,以期为从事遗传及性染色体进化的研究者提供参考。     

The organization and evolution of the human Y chromosome

The recent sequencing of a large chunk of euchromatin from the human Y chromosome is a technical tour de force. It answers some evolutionary questions about this unusual chromosome while raising others.     

Mitochondrial mutations may drive Y chromosome evolution

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which impair male fertility and ultimately lead to a reduction in the effective population size (N(e)) and consequently the variability of the Y chromosome.     

HUMAN CHROMOSOME Y AND SRY

The precise location of the SRY gene on the human Y chromosome has been revealed through studies of sex reversal cases involving deletion, cross-linking and mutations of the SRY gene. Its DNA sequence and mechanism of action are being understood. Similarity of SRY with Sry of mice and its interaction with other genes in male sex determination are discussed.     

The human Y chromosome, in the light of evolution

Most eukaryotic chromosomes, akin to messy toolboxes, store jumbles of genes with diverse biological uses. The linkage of a gene to a particular chromosome therefore rarely hints strongly at that gene's function. One striking exception to this pattern of gene distribution is the human Y chromosome. Far from being random and diverse, known human Y-chromosome genes show just a few distinct expression profiles. Their relative functional conformity reflects evolutionary factors inherent to sex-specific chromosomes.     

An adaptive hypothesis for the evolution of the Y chromosome.

Population geneticists remain unsure of the forces driving the evolution of Y chromosomes. Here we consider the possibility that the degeneration of the Y reflects its inability to evolve adaptively. Because the overwhelming majority of favorable mutations on a nonrecombining proto-Y suffer a zero probability of fixation, the fitness of the Y must lag far behind that of the recombining X. At some point, this disparity will grow so large that selection favors an increase in the expression of (fit) X-linked alleles and a decrease in the expression of (unfit) Y-linked alleles. Our calculations suggest that this process acts far more rapidly than hitchhiking-induced erosion of the Y and at least as rapidly as the fixation of deleterious alleles on the Y by background selection. Most important, this hypothesis can explain the evolution of Y chromosomes in taxa such as Drosophila that have very large population sizes.     

Defective calmodulin-mediated nuclear transport of the sex-determining region of the Y chromosome (SRY) in XY sex reversal

The sex-determining region of the Y chromosome (SRY) plays a key role in human sex determination, as mutations in SRY can cause XY sex reversal. Although some SRY missense mutations affect DNA binding and bending activities, it is unclear how others contribute to disease. The high mobility group domain of SRY has two nuclear localization signals (NLS). Sex-reversing mutations in the NLSs affect nuclear import in some patients, associated with defective importin-beta binding to the C-terminal NLS (c-NLS), whereas in others, importin-beta recognition is normal, suggesting the existence of an importin-beta-independent nuclear import pathway. The SRY N-terminal NLS (n-NLS) binds calmodulin (CaM) in vitro, and here we show that this protein interaction is reduced in vivo by calmidazolium, a CaM antagonist. In calmidazolium-treated cells, the dramatic reduction in nuclear entry of SRY and an SRY-c-NLS mutant was not observed for two SRY-n-NLS mutants. Fluorescence spectroscopy studies reveal an unusual conformation of SRY.CaM complexes formed by the two n-NLS mutants. Thus, CaM may be involved directly in SRY nuclear import during gonadal development, and disruption of SRY.CaM recognition could underlie XY sex reversal. Given that the CaM-binding region of SRY is well-conserved among high mobility group box proteins, CaM-dependent nuclear import may underlie additional disease states.     

Characterization and evolution of a single-copy sequence from the human Y chromosome.

To study the evolution and organization of DNA from the human Y chromosome, we constructed a recombinant library of human Y DNA by using a somatic cell hybrid in which the only cytologically detectable human chromosome is the Y. One recombinant (4B2) contained a 3.3-kilobase EcoRI single-copy fragment which was localized to the proximal portion of the Y long arm. Sequences homologous to this human DNA are present in male gorilla, chimpanzee, and orangutan DNAs but not in female ape DNAs. Under stringent hybridization conditions, the homologous sequence is either a single-copy or a low-order repeat in humans and in the apes. With relaxed hybridization conditions, this human Y probe detected several homologous DNA fragments which are all derived from the Y in that they occur in male DNAs from humans and the apes but not in female DNAs. In contrast, this probe hybridized to highly repeated sequences in both male and female DNAs from old world monkeys. Thus, sequences homologous to this probe underwent a change in copy number and chromosomal distribution during primate evolution.     

Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

Background  

One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY) receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes) and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10.     

Assignment of SRY, ANT3, and CSF2RA to the bovine Y chromosome by FISH and RH mapping

Three genes, SRY, ANT3, and CSF2RA, were mapped to the bovine Y chromosome (BTAY) by fluorescence in situ hybridization (FISH) and/or radiation hybrid (RH) mapping. FISH analysis indicated that the bovine SRY gene maps to the distal region of BTAYq, while ANT3 and CSF2RA are located in the pseudoautosomal region (PAR) of BTAYp and BTAXq. RH mapping with a 7000-rad cattle hamster whole-genome radiation hybrid panel further defined the ANT3 and CSF2RA position in relationship to previously mapped 12 PAR markers, and resulted in a relatively high resolution RH map for the PAR of BTAY.     

Mammalian sex-chromosome evolution: a conserved homoeologous segment on the X and Y chromosomes in primates

In a representative sample of primate species, including simians (Catarrhini and Platyrrhini) and prosimians (Lemuriformes and Lorisiformes), high-resolution, early replication banding revealed a homoeologous early replicating segment at the ends of both sex chromosomes. The DXYZ2 element, a repeated sequence specific for the human pseudoautosomal region, is conserved in the genomes of all primate species studies and is specifically localized in the distal early replicating segments of the X and Y chromosomes. Thus, cytogenetic and molecular evidence is presented of a highly conserved sex-chromosomal segment in primates. The pseudoautosomal behavior of this segment is discussed.     

Mammalian karyotype evolution

The chromosome complements (karyotypes) of animals display a great diversity in number and morphology. Against this background, the genomes of all species are remarkably conserved, not only in transcribed sequences, but also in some chromosome-specific non-coding sequences and in gene order. A close examination with chromosome painting shows that this conservation can be resolved into small numbers of large chromosomal segments. Rearrangement of these segments into different combinations explains much of the observed diversity in species karyotypes. Here we discuss how these rearrangements come about, and show how their analysis can determine the evolutionary relationships of all mammals and their descent from a common ancestor.