Genome data have revealed great variation in the numbers of genes in different organisms, which indicates that there is a fundamental process of genome evolution: the origin of new genes. However, there has been little opportunity to explore how genes with new functions originate and evolve. The study of ancient genes has highlighted the antiquity and general importance of some mechanisms of gene origination, and recent observations of young genes at early stages in their evolution have unveiled unexpected molecular and evolutionary processes.

/pdf/the-origin-of-new-genes-glimpses-from-the-young-and-old-udlond2scr.pdf

The origin of new genes: glimpses from the young and old

The X-linked Xist gene encodes a large untranslated RNA that has been implicated in mammalian dosage compensation and in spermatogenesis. To investigate the function of the Xist gene product, we have generated male and female mice that carry a deletion in the structural gene but maintain a functional Xist promoter. Mutant males were healthy and fertile. Females that inherited the mutation from their mothers were also normal and had the wild-type paternal X chromosome inactive in every cell. In contrast to maternal transmission, females that carry the mutation on the paternal X chromosome were severely growth-retarded and died early in embryogenesis. The wild-type maternal X chromosome was inactive in every cell of the growth-retarded embryo proper, whereas both X chromosomes were expressed in the mutant female trophoblast where X inactivation is imprinted. However, an XO mouse with a paternally inherited Xist mutation was healthy and appeared normal. The imprinted lethal phenotype of the mutant females is therefore due to the inability of extraembryonic tissue with two active X chromosomes to sustain the embryo. Our results indicate that the Xist RNA is required for female dosage compensation but plays no role in spermatogenesis.

/pdf/xist-deficient-mice-are-defective-in-dosage-compensation-but-6jw5xeaxcy.pdf

Xist-deficient mice are defective in dosage compensation but not spermatogenesis.

https://www.cell.com/cell/pdf/S0092-8674(13)00205-5.pdf

X-Inactivation, Imprinting, and Long Noncoding RNAs in Health and Disease

A vast array of successive epigenetic modifications ensures the creation of a healthy individual. Crucial epigenetic reprogramming events occur during germ cell development and early embryogenesis in mammals. As highlighted by the large offspring syndrome with in vitro conceived ovine and bovine animals, any disturbance during germ cell development or early embryogenesis has the potential to alter epigenetic reprogramming. Therefore the complete array of human assisted reproductive technology (ART), starting from ovarian hormonal stimulation to embryo uterine transfer, could have a profound impact on the epigenetic state of human in vitro produced individuals. Although some investigators have suggested an increased incidence of epigenetic abnormalities in in vitro conceived children, other researchers have refuted these allegations. To date, multiple reasons can be hypothesized why irrefutable epigenetic alterations as a result of ART have not been demonstrated yet.

/pdf/epigenetics-definition-mechanisms-and-clinical-perspective-3pah9sd8r5.pdf

Epigenetics: definition, mechanisms and clinical perspective.

Sex chromosomes are primary determinants of sexual dimorphism in many organisms. These chromosomes are thought to arise via the divergence of an ancestral autosome pair and are almost certainly influenced by differing selection in males and females. Exploring how sex chromosomes differ from autosomes is highly amenable to genomic analysis. We examined global gene expression in Drosophila melanogaster and report a dramatic underrepresentation of X-chromosome genes showing high relative expression in males. Using comparative genomics, we find that these same X-chromosome genes are exceptionally poorly conserved in the mosquito Anopheles gambiae. These data indicate that the X chromosome is a disfavored location for genes selectively expressed in males.

https://science.sciencemag.org/content/sci/299/5607/697.full.pdf

Paucity of Genes on the Drosophila X-Chromosome Showing Male-Biased Expression

Inactivation of the single X chromosome in the primary spermatocytes of species with heterogametic males is postulated as a basic control mechanism on the chromosomal level that is required for normal spermatogenesis. This view is supported by (a) cytological observations of X-chromosome allocycly in the primary spermatocytes of all male-heterogametic organisms that were adequately examined, (b) autoradiographic evidence of early cessation of transcription by the X chromosome in the mouse and three species of grasshopper, and (c) the male sterility of animals with certain X-chromosome rearrangements that cannot be attributed to misfunction of specific genes. X-chromosome inactivation during spermatogenesis is proposed as the ideal system for studies of genetic control at the chromosomal level.

https://www.pnas.org/content/pnas/69/1/182.full.pdf

The Role of X-Chromosome Inactivation during Spermatogenesis

Inactivation of the single X chromosome in the primary spermatocytes of species with hetero- gametic males is postulated as a basic control mechanism on the chromosomal level that is required for normal spermatogenesis. This view is supported by (a) cytological observations of X-chromosome allocycly in the primary spermatocytes of all male-heterogametic organisms that were adequately examined, (b) autoradiographic evidence of early cessation of transcription by the X chromosome in the mouse and three species of grasshopper, and (c) the male sterility of animals with certain X-chromosome rearrangements that cannot be attributed to misfunction of specific genes. X-chromosome inactivation during spermatogenesis is proposed as the ideal system for studies of genetic control at the chromosomal level. Sex chromosomes provide a striking example of differentia- tion of the chromosomal complement and inferentially of chro- mosomal function during evolution. It seems reasonable to suppose that natural selection has resulted in a particular distribution of genes between the sex chromosomes and the autosomes that is related to the role of these genes in the development and expression of sexuality. For example, male- fertility genes are found on the Y chromosome (Y) in Droso- phila, whereas male-determining genes are found on mammal- ian Y chromosomes. Furthermore, sexual differentiation might depend on males differing in constitution from females (e.g. dosage) with respect to some genes but not others; Bridges' and Goldschmidt's genie balance theories of sex determination (1, 2) are based on such a requirement. If accompanying sex chromosome evolution there were the concomitant evolution of a chromosomal mechanism permitting coordinate control of sex-linked gene function, then the potential of functioning in coordination with other sex-linked genes might favor the location of certain loci on the sex chromosome. That such control could have developed is evident from other forms of control operating at the chromosomal level. For example, coordinate control of chromosomal activity is evident in all eukaryotic organisms at mitosis; furthermore, asynchro- nous control of different chromosomes or chromosome seg- ments may be inferred from their allocycly (differences in chromosome condensation) during the cell cycle. Inactivation of one X chromosome (X) in somatic cells of female mammals (3) or of the entire paternally inherited chromosome set in certain coccids (4), as well as the physical elimination of chromosomal material from cell lines (5, 6), are other examples of gene inactivation at the chromosomal level. We conclude that the evolution of both genie and chromosomal processes

Eliezer Lifschytz

Papers

The Role of X-Chromosome Inactivation during Spermatogenesis

The Role of X-Chromosome Inactivation d (Drosophila/allocycly/chromosome evolution/male sterili