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The evolutionary forces underlying the rapid evolution in sequences and functions of new genes remain a mystery. Adaptation by natural selection explains the evolution of some new genes. However, many new genes perform sex-biased functions that have rapidly evolved over short evolutionary time scales, suggesting that new gene evolution may often be driven by conflicting selective pressures on males and females. It is well established that such sexual conflict (SC) plays a central role in maintaining phenotypic and genetic variation within populations, but the role of SC in driving new gene evolution remains essentially unknown. This review explores the connections between SC and new gene evolution through discussions of the concept of SC, the phenotypic and genetic signatures of SC in evolving populations, and the molecular mechanisms by which SC could drive the evolution of new genes. We synthesize recent work in this area with a discussion of the case of Apollo and Artemis, two extremely young genes (<200,000 years) in Drosophila melanogaster, which offered the first empirical insights into the evolutionary process by which SC could drive the evolution of new genes. These new duplicate genes exhibit the hallmarks of sexually antagonistic selection: rapid DNA and protein sequence evolution, essential sex-specific functions in gametogenesis, and complementary sex-biased expression patterns. Importantly, Apollo is essential for male fitness but detrimental to female fitness, while Artemis is essential for female fitness but detrimental to male fitness. These sexually antagonistic fitness effects and complementary changes to expression, sequence, and function suggest that these duplicates were selected for mitigating SC, but that SC has not been fully resolved. Finally, we propose Sexual Conflict Drive as a self-driven model to interpret the rapid evolution of new genes, explain the potential for SC and sexually antagonistic selection to contribute to long-term evolution, and suggest its utility for understanding the rapid evolution of new genes in gametogenesis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A hallmark of aging is the progressive accumulation of cellular damage. Age-induced damage arises due to a decrease in organelle function along with a decline in protein quality control. Although somatic tissues deteriorate with age, the germline must maintain cellular homeostasis in order to ensure the production of healthy progeny. While germline quality control has been primarily studied in multicellular organisms, recent evidence suggests the existence of gametogenesis-specific quality control mechanisms in unicellular eukaryotes, highlighting the evolutionary conservation of meiotic events beyond chromosome morphogenesis. Notably, budding yeast eliminates age-induced damage during meiotic differentiation, employing novel organelle and protein quality control mechanisms to produce young and healthy gametes. Similarly, organelle and protein quality control is present in metazoan gametogenesis; however, whether and how these mechanisms contribute to cellular rejuvenation requires further investigation. Here, we summarize recent findings that describe organelle and protein quality control in budding yeast gametogenesis, examine similar quality control mechanisms in metazoan development, and identify research directions that will improve our understanding of meiotic cellular rejuvenation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The reproductive cycle of teleost fishes is regulated by the brain-pituitary-gonad (BPG) axis. The transcription profile of genes involved in the reproduction signalling in the BPG-axis differs in females and males during the gametogenic cycle. Impacts of endocrine disrupting chemicals on these signalling pathways in fish are known, but the participation of the BPG-axis in the development of the intersex condition is not well understood. Intersex thicklip grey mullets (Chelon labrosus) have been identified in several estuaries from the SE Bay of Biscay, revealing the presence of feminizing contaminants in the area. In previous studies, transcription patterns of genes related with steroidogenesis and gamete growth have been shown to differ among female, male and intersex mullets. However, many components of the reproduction control have not been studied yet. The aim of this study was to assess the transcription levels of target BPG-axis genes in female, male and intersex mullets captured in the polluted harbour of Pasaia, during their gametogenic cycle. After histologically examining the gonads, the transcription levels of previously sequenced target genes were measured by qPCR: kiss2, gpr54 and gnrh1 in brain, fshβ and lhβ in pituitary and fshr and lhr in gonads. In both females and males, brain genes were most transcribed in early gametogenesis, proving their relevance in the onset of both oogenesis and spermatogenesis. Pituitary gonadotropins in females showed upregulation as oogenesis progressed, reaching the highest transcription levels at vitellogenic stage, while in males transcript levels were constant during spermatogenesis. Transcription levels of gonadotropin receptors showed different patterns in ovaries and testes, suggesting differing function in relation to gametogenesis and maturation. Intersex mullets showed transcription levels of brain target genes similar to those observed in females at cortical alveoli stage and to those in mid spermatogenic males. In intersex testes the transcription pattern of gonadotropin receptor fshr was downregulated in comparison to non-intersex testes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

PIWI-interacting RNAs (piRNAs) are abundantly found in germ cells and involved in gametogenesis and gonadal development. Information on the regulatory roles of piRNAs in crustacean reproduction, however, is scarce. Thus, we identified gonadal piRNAs of mud crab Scylla paramamosain. Of the 115,491 novel piRNAs, 596 were differentially expressed. Subsequently, 389,887 potential piRNA-target genes were predicted. The expression of 4 piRNAs and 9 genes with high piRNA interactions were validated with the inclusion of additional immature specimens, including LRP2 that is involved in growth and reproduction, MDN1 in ribosome biogenesis pathway and gametogenesis, and PRKDC, a DNA repair gene involved in gonadal differentiation and maturation. KEGG analysis further revealed the involvement of predicted piRNA target genes in gametogenesis- and reproduction-related pathways. Our findings provide baseline information of mud crab piRNAs and their differential expression between testes and ovaries suggests that piRNAs play an essential role in regulating gametogenesis and gonadal development., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The Atlantic Bluefin Tuna (ABFT, Thunnus thynnus) is one of the most intensely exploited fisheries resources in the world. In spite of the years of studies on ABFT, basic aspects of its reproductive biology remain uncertain. To gain insight regarding the seasonal changes of the reproductive characteristics of the eastern stock of ABFT, blood and tissue samples were collected from mature specimens caught in the Mediterranean basin during the reproductive (May-June) and non-reproductive season (Oct-Nov). Histological analysis of the gonads of May-June samples indicated that there were females which were actively spawning (contained post-ovulatory follicles) and females that were not actively spawning that had previtellogenic and fully vitellogenic oocytes. In males, testis were at early or late stage of spermatogenesis during the reproductive season. In Oct-Nov, ovaries contained mostly previtellogenic oocytes as well as β and α atretic follicles while the testis predominantly contained spermatogonia and few cysts with spermatocytes and spermatozoa. Gonadosomatic index (GSI) in females was highest among the actively spawning individuals while in males GSI was higher in early and late spermatogenic individuals compared to those that were spent. Plasma sex steroids levels varied with the reproductive season. In females, estradiol (E 2 ), was higher in May-June while testosterone (T) and progesterone (P) did not vary. In males, E 2 and T were higher in May-June while P levels were similar at the two sampling points. Circulating follicle stimulating hormone (FSH) was higher in Oct-Nov than in May-June both in males and females. Vitellogenin (VTG) was detected in plasma from both males and females during the reproductive season with levels in females significantly higher than in males. VTG was undetected in Oct-Nov samples. Since choriogenesis is an important event during follicle growth, the expression of three genes involved in vitelline envelope formation and hardening was measured and results showed significantly higher levels in ovaries in fish caught in May-June with respect to those sampled in Oct-Nov. In addition, a set of genes encoding for ion channels that are responsible for oocyte hydration and buoyancy, as well as sperm viability, were characterized at the two time points, and these were found to be more highly expressed in females during the reproductive season. Finally, the expression level of three mRNAs encoding for different lipid-binding proteins was analyzed with significantly higher levels detected in males, suggesting sex-specific expression. Our findings provide additional information on the reproductive biology of ABFT, particularly on biomarkers for the assessment of the state of maturation of the gonad, highlighting gender-specific signals and seasonal differences., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Efforts to establish an aquaculture industry for sablefish (Anoplopoma fimbria) are constrained by reproductive dysfunction in wild-caught fish and by lack of reproduction of F1 females. Toward a better understanding of the reproductive dysfunction of captive broodstock, full-length cDNAs encoding the sablefish gonadotropin subunits (fshb, lhb and cga) and their receptors (fshr and lhcgr) were cloned, sequenced and quantitative real-time PCR assays developed. Sablefish gonadotropin subunits display some unique features, such as two additional Cys residues in the N-terminal region of Fshb and a lack of potential N-glycosylation sites in Fshb and Lhb, whereas Fshr and Lhcgr possess conserved structural characteristics described in other vertebrates. Wild females captured in fall completed gametogenesis in captivity the next spawning season, whereas females captured three months earlier, during summer, failed to mature. Interestingly, these wild non-maturing females exhibited similar reproductive features as prepubertal F1 females, including low levels of pituitary gonadotropin and ovarian receptor mRNAs and plasma sex steroids, and ovarian follicles arrested at the perinucleolus stage. In conclusion, this study described the cloning, molecular characterization and development of qPCRs for sablefish gonadotropins and their receptors. Rearing conditions may impair vitellogenic growth of ovarian follicles in sablefish, compromising the reproductive success of broodstock., (Published by Elsevier Inc.)

The present study characterized changes in key parameters of reproduction in adult roach (Rutilus rutilus) from Lake Grosser Mueggelsee (Berlin, Germany) during natural gametogenesis. Fish of both sexes were sampled in monthly intervals between April and August in order to cover the onset of gametogenesis. Investigated parameters included gonad histology, plasma levels of 17β-oestradiol (E2), testosterone (T), 11-ketotestosterone (11-KT), and 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) as well as the expression of gonadotropin subunits in the pituitary. Furthermore, the mRNA-expression of brain-type aromatase (cyp19a1b), androgen receptor (ar), and estrogen receptor isoforms was studied at the pituitary level. The onset of gametogenesis - as indicated by follicles with cortical alveoli in females and first spermatogonia B in males - was observed in July, accompanied by a significant up-regulation of follicle-stimulating hormone β (fshβ) mRNA in the pituitary in both sexes. On the other hand, luteinizing hormone β (lhβ) mRNA increased later on in August. In males, the increase of fshβ mRNA in July coincided with a rise in plasma 11-KT concentrations. In females, E2 in plasma increased later, not until August, shortly before true vitellogenesis (late cortical alveoli stage). Expression of sex steroid receptors in the pituitary revealed only minor seasonal fluctuations. Most pronounced, ar mRNA displayed the highest level pre-spawning in both sexes. Interestingly, cyp19a1b mRNA-expression in the pituitary increased in parallel with fshβ already before any changes in plasma E2 or T occurred. These data suggest an important role of pituitary FSH and aromatase at the onset of gametogenesis in the roach., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Mature gametocytes, the sexual stage of Plasmodium falciparum, ensure the continued transmission of malaria from the human host to the mosquito vector. Even if gametocytes are not implicated in the malaria physiopathology it is crucial to the spread of malaria. Gametocytes are to be a key target for drugs used against Plasmodium in public health. The expression levels of 4 sexual-stage specific genes, Pfs 16, Pfs 25, Pfg 27 and S 18S rRNA, during gametocytogenesis of various P. falciparum strains were analyzed by a real time PCR assay. The strains showed different capacities to produce mature gametocytes and in parallel different patterns of sexual gene expression. There was a correlation only between Pfs 16 cDNA overexpression in the first 48h of the culture and the production of mature gametocytes. Pfs 16 is an early marker of the development of mature gametocytes in cultures and is therefore a potential target for new antimalarial drugs.

Triploid fishes generally show sterility along with retarded gonadal development and aneuploid gametes. In teleosts, thyroid hormones influence seasonal adaptations and annual events such as reproduction. In addition, thyroid hormone deposition in matured ova is important for reproductive success as the role of thyroid hormones in early development and metamorphosis is well established. The present study deals with measurements of free and total thyroxine (T4) and triiodothyronine (T3) in the plasma of triploid and diploid catfish Heteropneustes fossilis (Bloch) in a complete reproductive cycle. Accumulations of total T4 and T3 within the oocytes have also been measured during the spawning period from fishes of both ploidy groups. No difference of plasma free hormones was noticed between the diploids and triploids of both the sexes in any period of reproductive cycle, although, seasonal variations were noted in both the groups. A significant decrease in the total thyroid hormone levels was noticed in plasma of the diploids in the spawning period compared to triploid fish. During the same period, accumulation of THs was significantly higher in the oocytes of diploids than that of the triploids. Thyroid gland structure also revealed a higher state of activity in the female diploids than the triploids during spawning period. Lower activity of thyroid tissue, higher levels of THs in plasma, and lower accumulation of maternally derived hormones in the oocytes of triploid females during spawning period may be associated with sterility of triploids.

Imprinted genes are characterized by predominant expression from one parental allele and differential DNA methylation. Few imprinted genes have been found to acquire a methylation mark in the male germ line, however, and only one of these, H19, has been studied in detail. We examined methylation of the Rasgrf1 and Gtl2 differentially methylated regions (DMR) to determine whether methylation is erased in male germ cells at e12.5 and when the paternal allele acquires methylation. We also compared their methylation dynamics with those of H19 and the maternally methylated gene Snrpn. Our results show that methylation is erased on Rasgrf1, H19, and Snrpn at e12.5, but that Gtl2 retains substantial methylation at this stage. Erasure of methylation marks on Gtl2 appears to occur later in female germ cells to give the unmethylated profile seen in mature MII oocytes. In the male germ line, de novo methylation of Rasgrf1, Gtl2, and H19 occurs in parallel between e12.5 and e17.5, but the DMR are not completely methylated until the mature sperm stage, suggesting a methylation dynamic different from that of IAP, L1, and minor satellite sequences, which have been shown to become fully methylated by e17.5 in male germ cells. This study also indicates important differences between different imprinted DMR in timing and extent of methylation in the germ cells.

Nhlh2 is a member of the basic helix-loop-helix (bHLH) transcription factor family and is expressed in developing and adult neuroendocrine tissues such as the pituitary and hypothalamus. Targeted deletion of Nhlh2 (N2KO) in mice results in hypogonadism and obesity. While gonadally intact male N2KO mice are infertile and lack male sexual behavior, female N2KO mice can become pregnant and carry litters to full term. Unlike normal females in which fertility averages 8-12 months with approximately one pregnancy per month, N2KO females have a shorter reproductive span with most females supporting only three to four pregnancies in a 9-month period. In addition, N2KO females exhibit abnormal estrous cycles characterized by a truncated estrus and a prolonged proestrus. We have found that while young female N2KO mice ovulate the same number of oocytes as normal females in response to exogenous hormones, the number of oocytes released by aged N2KO females is reduced over 50%. Interestingly, oocytes from N2KO females are equally competent for in vitro fertilization assays when compared to oocytes from similarly aged normal and heterozygous mice. We have further demonstrated that both young and old N2KO females show at least a 50% reduction in hormone-stimulated sexual behavior as measured by their lordosis quotient. This suggests that N2KO females show a lifelong behavioral hyporesponsiveness to exogenous steroid hormones accompanied by a reduction in reproductive longevity via reduced ovulation with aging. Potential gene regulatory mechanisms that involve the action of the Nhlh2 transcription factor on female fertility and sexual behavior are discussed.

DNA methylation differences between maternal and paternal alleles of many imprinted genes are inherited from the male and female gametes and subsequently maintained during development. However, the stages of gametogenesis during which methylation imprints are established have not been well defined. In this study, we used bisulfite sequencing to determine the methylation dynamics of the imprinted genes small nuclear ribonucleoprotein N (Snrpn), insulin-like growth factor 2 receptor (Igf2r), mesoderm-specific transcript (Mest; formerly Peg1), paternally expressed gene 3 (Peg3), and H19 fetal liver mRNA (H19). We identified regions in the maternally imprinted genes (Snrpn, Mest, and Peg3) that were unmethylated in sperm but 100% methylated in mature oocytes. Igf2r, which is expressed from the maternal allele, was completely methylated within intronic differentially methylated region 2 in oocytes and unmethylated in sperm. The 5' region of H19, a paternally imprinted gene, was completely methylated in sperm and unmethylated in oocytes. We examined the methylation status of Snrpn during oocyte growth and maturation. Whereas the DNA of non-growing oocytes was mostly unmethylated, mid-size growing oocytes had a mosaic pattern of allelic methylation, and full acquisition of the methylation imprint was complete by metaphase II. We have identified regions within imprinted genes that show gamete-specific methylation patterns in mature germ cells and demonstrated that maternal methylation imprints on at least one imprinted gene, Snrpn, are established during the postnatal growth phase of oogenesis. Thus, whereas paternal imprints seem to be established early (in diploid gonocytes well before the onset of meiosis), maternal imprints are established late (in growing oocytes that are arrested in the diplotene stage of meiosis). These findings raise the possibility that assisted reproductive technologies that involve in vitro maturation of oocytes may result in developmental abnormalities due to incomplete methylation imprints in immature oocytes.

With the Plasmodium falciparum genome sequencing near completion, functional analysis of individual parasite genes has become the major task of the postgenomic era. Understanding the expression patterns of individual genes is the initial step toward this goal. In this report, we have examined gene expression during gametocytogenesis of the malaria parasite, P. falciparum, using a modified differential display (DD) method. The modifications of this method include adjusting the dNTP mix, using upstream primers with higher AT contents, and reducing the extension temperature of the polymerase chain reaction (PCR). With a combination of 16 arbitrary upstream primers and 3 one-base-anchored oligo(dT) primers, we have successfully cloned 80 unique cDNA tags from stage IV-V gametocytes. Further analysis by dot blots and semiquantitative reverse transcriptase-PCR showed that at least 49 cDNAs had induced or elevated levels of expression in gametocytes. These results indicate that this modified DD procedure is suitable for large-scale identification of developmentally regulated genes in the AT-rich Plasmodium genome., (Copyright 2001 Elsevier Science (USA).)

To clarify the profiles of two distinct gonadotropin (GTH-I and -II) mRNA levels during gametogenesis in a multiple spawner, the Japanese flounder (Paralichthys olivaceus), the cDNAs encoding GTH-Ibeta and -IIbeta from the pituitary gland have been cloned and sequenced. The nucleotide sequence of GTH-Ibeta was 542 bp long, encoding 120 amino acids, and that of GTH-IIbeta was 554 bp long, encoding 145 amino acids. In females, Northern blot analysis has revealed that relative mRNA levels of GTH-Ibeta and -IIbeta were low in immature fish, showed a gradual increase with ovarian development, and reached the highest level at the maturation stage. Both GTH-Ibeta and -IIbeta mRNA levels were highly correlated with gonadosomatic index (GSI) values and with circulating estradiol-17beta and testosterone (T) levels. In males, the mRNA levels of GTH-Ibeta increased with the increase in GSI values and in circulating 11-ketotestosterone and T levels, whereas the mRNA levels of GTH-IIbeta did not show any correlation with GSI values and with circulating steroid levels, suggesting a difference in regulatory mechanisms of GTH-I and -II synthesis in males. The similar changes in GTH-Ibeta and -IIbeta mRNA levels during oogenesis are considered to be characteristic of GTH synthesis in multiple spawners, differing from the differential changes reported in annual spawners such as salmonids., (Copyright 2001 Academic Press.)

We previously reported that karyotype and gametocyte-producer mutants spontaneously arose during in vivo asexual multiplication of Plasmodium berghei. Here we studied the rate of selection of these mutants in vivo. Gametocyte production and karyotype pattern were established at regular intervals during prolonged periods of asexual multiplication of clone 8417 of P. berghei. We found that karyotype mutants and mutants which do not produce gametocytes can replace the original high-producer parasites of clone 8417 within several weeks. The time at which mutants became predominant in the population in different experiments, however, differed greatly. Mutants with intermediate or low gametocyte production were not found. In experimentally mixed infections, containing parasites from two clones from different strains (clone 8417 of the ANKA strain; clone 1 of the K173 strain), high-producer parasites of clone 8417 were overgrown by parasites of the nonproducer clone. Nonproducer mutants from the originally high-producer clone 8417, however, were able to coexist with parasites of the nonproducer clone. These results demonstrate that in our experiments nonproducer parasites had a strong selective advantage during asexual multiplication compared to high producers. All karyotype mutants which became predominant in our experiments were nonproducers. In two experiments a change in karyotype coincided with the loss of gametocyte production which may suggest a causal relationship between these events.