Left panel: short green irregular lines arranged in pairs. Right: Close up of one pair shows that the two strands form a cross shape.
Paired chromosomes showing crossovers in a mouse oocyte.
Hunter lab.
This article continues my series exploring the many ways in which the human body demonstrates unintelligent design. Far from being the perfect handiwork of a benevolent creator, our anatomy and physiology are full of flaws, inefficiencies, and dangerous vulnerabilities. Each of these makes sense in light of evolution by natural selection—an opportunistic, short-term process that tinkers with existing structures—but they make no sense at all if we are supposed to be the product of an all-wise designer.
Creationists often argue from a position of ignorant incredulity, claiming that complexity implies intelligent design, when in fact the opposite is true. The hallmark of good, intelligent design is simplicity, for two very simple reasons: first, simple things are easier to construct and require fewer resources; and second, simple structures and processes have fewer potential points of failure, making them more reliable.
In short: complexity is evidence against intelligent design and in favour of a mindless, utilitarian, natural process such as evolution.
In addition to being minimally complex, another characteristic we would expect of something designed by an omniscient, maximally intelligent, and benevolent designer is that the process should work perfectly, every time, without fail.
The problem for creationists is that their favourite example of supposed intelligent design — the human body — is riddled with complexity in both its structures and processes. This complexity provides countless examples of systems that fail to perform adequately, or fail altogether, with varying frequency. Many failures occur in the layers of complexity needed to control or compensate for the inadequacies of other systems, and when those compensatory mechanisms themselves fail, the result can be a cascade of dysfunctions or processes running out of control. The consequences manifest as diseases, defects, and disabilities — hardly the work of an all-wise designer.
They are, however, exactly what we would expect from a mindless, utilitarian process like evolution, which prioritises short-term survival and reproduction, selecting only what is better — sometimes only marginally better — than what preceded it, rather than seeking optimal solutions. I have catalogued many such suboptimal compromises in the anatomy and physiology of the human body, and the problems that arise from them, in my book, The Body of Evidence: How the Human Body Refutes Intelligent Design, one of my Unintelligent Design series.
Just yesterday, I wrote about research suggesting that autism may be a by-product of the rapid evolution of intelligence in humans. Now we have another striking example of extreme biological complexity which, when it goes wrong, can have catastrophic consequences: the production of eggs in women and sperm cells in men.
Background^ How Humans Produce Eggs and Sperm. Egg production (oogenesis)This research, led by Professor Neil Hunter of the Department of Microbiology and Molecular Genetics at the University of California, Davis, has been published open access in Nature and summarised in a UC Davis news article by Douglas Fox.
- In females, all the eggs a woman will ever have are formed before birth. During foetal development, cells in the ovaries undergo meiosis (a special type of cell division that halves the number of chromosomes).
- These immature egg cells (oocytes) remain “frozen” in an early stage until puberty, when hormones begin to stimulate their monthly maturation.
- Usually, only one egg completes development and is released each month during ovulation.
- Because oocytes are stored for decades, they accumulate damage and errors over time, which explains why fertility declines and the risk of genetic disorders rises with age.
Sperm production (spermatogenesis)
- In males, sperm are produced continuously from puberty onwards in the testes.
- Specialised stem cells divide by meiosis to create sperm cells with half the normal number of chromosomes.
- Each cell division cycle produces millions of sperm every day, but the process is intricate and vulnerable to errors.
- Defective sperm are common, though usually filtered out, and sperm quality can decline with age, illness, or environmental factors.
Why it matters
Both processes rely on precise chromosome sorting and pairing. Even small mistakes—such as an extra or missing chromosome—can lead to infertility, miscarriage, or genetic disorders such as Down syndrome. The complexity and fragility of gamete production underline how far these processes fall short of “perfect design”.
In addition, as this article exposes, the eggs are maintained in a state of partial meiosis, 'frozen' at a critical point, sometimes for several decades, until just before ovulation, requiring special processes to conserve them in that state. If this stage fails then it can result in miscarriage, or birth defects.
Landmark Discovery Reveals How Chromosomes Are Passed From One Generation to the Next
Critical Event Guides Accurate Distribution of Chromosomes To Eggs and Sperm
When a woman becomes pregnant, the outcome of that pregnancy depends on many things — including a crucial event that happened while she was still growing inside her own mother’s womb. It depends on the quality of the egg cells that were already forming inside her fetal ovaries. The DNA-containing chromosomes in those cells must be cut, spliced and sorted perfectly. In males, the same process produces sperm in the testes but occurs only after puberty.
If that goes wrong, then you end up with the wrong number of chromosomes in the eggs or sperm. This can result in infertility, miscarriage or the birth of children with genetic diseases.
Professor Neil Hunter, corresponding author
Department of Microbiology and Molecular Genetics
University of California Davis
Davis, CA, USA.
In a paper published Sept. 24 in the journal Nature, Hunter’s team reports a major new discovery about a process that helps safeguard against these mistakes. He has pieced together the choreography of proteins that connect matching chromosome pairs — ensuring that they are sorted correctly as egg and sperm cells develop and divide.
Hunter’s discoveries required methods to watch the molecular events of chromosome recombination unfold with unprecedented detail. This involved genetic engineering in budding yeast — a model organism that has been used for decades to discover how fundamental cellular processes work.
The chromosome structures that we studied have changed very little across evolution. Every protein that we looked at in yeast has a direct counterpart in humans.
Professor Neil Hunter.
His findings could improve our understanding of fertility problems and how they are diagnosed and treated in humans.
Forming chromosome crossovers for strong connections
Humans have 46 chromosomes in each of our cells, made up of 23 pairs of matching, “homologous” chromosomes, with one of each pair inherited from each parent. Early in the process of making sperm or eggs, those chromosome pairs line up, and the parental chromosomes break and rejoin to each other. These chromosome exchanges, called “crossovers,” serve two important functions.
First, they help ensure that each chromosome that is passed on to the offspring contains a unique mixture of genes from both parents. Crossovers also keep the chromosomes connected in matching pairs. These connections guide the distribution of chromosomes when cells divide to produce eggs and sperm. Maintaining crossover connections is especially crucial in females, Hunter said.
As chromosomes pair up in developing egg or sperm cells, matching DNA strands are exchanged and twined together over a short distance to form a structure called a “double Holliday junction.” DNA strands of this structure are then cut to join the chromosomes forming a crossover.
In males, developing immature sperm cells then immediately divide and distribute chromosomes to the sperm. In contrast, egg cells developing in the fetal ovary arrest their development after crossovers have formed. The immature egg cells can remain in suspended animation for decades after birth, until they are activated to undergo ovulation.
Left panel: short green irregular lines arranged in pairs. Right: Close up of one pair shows that the two strands form a cross shape. Paired chromosomes showing crossovers in a mouse oocyte.Hunter lab.
Only then does the process lurch back into motion: The egg cell finally divides, and the chromosome pairs that were connected by crossovers are finally separated to deliver a single set of chromosomes to the mature egg.
Maintaining the crossover connections over many years is a major challenge for immature egg cells.
Professor Neil Hunter.
If chromosome pairs aren’t connected by at least one crossover, they can lose contact with each other, like two people separated in a jostling crowd. This causes them to segregate incorrectly when the cell finally divides, producing egg cells with extra or missing chromosomes. This can cause infertility, miscarriage or genetic conditions such as Down syndrome, in which a child is born with an extra copy of chromosome 21, leading to cognitive impairment, heart defects, hearing loss and other problems.
From yeast to humans
Hunter has spent years trying to understand how crossovers form and how this process can fail and cause reproductive problems. By studying this process in yeast, researchers can directly visualize molecular events of double-Holliday junction resolution in synchronized populations of cells.
Researchers have identified dozens of proteins that bind and process these junctions. Hunter and then-postdoctoral fellow Shangming Tang (now an assistant professor of biochemistry and molecular genetics at the University of Virginia) used a technique called “real-time genetics” to investigate the function of those proteins. With this method, they made cells degrade one or more specific proteins within the junction-associated structures. They could then analyze the DNA from these cells, to see whether the junctions were resolved and if they formed crossovers. In this way, they built up a picture in which a network of proteins function together to ensure that crossovers are formed.
This strategy allowed us to answer a question that previously wasn’t possible.
Professor Neil Hunter.
They identified key proteins such as cohesin that prevent an enzyme called the STR complex (or Bloom complex in humans) from inappropriately dismantling the junctions before they can form crossovers.They protect the double Holliday junction. That is a key discovery.
Professor Neil Hunter.
This years-long research project in yeast is broadly relevant for human reproduction because the process has changed very little during evolution. Failure to protect double-Holliday junctions may be linked to fertility problems in humans.
In addition to Tang, the postdoc, seven undergraduates in the UC Davis College of Biological Sciences contributed to this work, including Jennifer Koo, Mohammad Pourhosseinzadeh, Emerald Nguyen, Natalie Liu, Christopher Ma, Hanyu Lu and Monica Lee.
Additional authors on the paper include Sara Hariri, Regina Bohn and John E. McCarthy, all members of the Hunter lab.
Publication:
Protecting double Holliday junctions ensures crossing over during meiosis Shangming Tang, Sara Hariri, Regina Bohn, John E. McCarthy, Jennifer Koo, Mohammad Pourhosseinzadeh, Emerald Nguyen, Natalie Liu, Christopher Ma, Hanyu Lu, Monica Lee & Neil HunterThis study highlights how even the fundamental processes of human reproduction are fragile, failure-prone, and riddled with inefficiencies. The intricate mechanisms required to produce eggs and sperm—the most basic requirement for life to continue—are full of potential points of breakdown. These flaws make perfect sense in light of evolution, a blind tinkerer that cobbles together workable solutions from existing parts, but they are utterly inconsistent with the idea of an intelligent, purposeful designer.
Abstract
Chromosomal linkages formed through crossover recombination are essential for the accurate segregation of homologous chromosomes during meiosis1. The DNA events of recombination are linked to structural components of meiotic chromosomes2. Imperatively, the biased resolution of double Holliday junction (dHJ) intermediates into crossovers3,4 occurs within the synaptonemal complex (SC), the meiosis-specific structure that mediates end-to-end synapsis of homologues during the pachytene stage5,6. However, the role of the SC in crossover-specific dHJ resolution remains unclear. Here we show that key SC components function through dependent and interdependent relationships to protect dHJs from aberrant dissolution into non-crossover products. Conditional ablation experiments reveal that cohesin, the core of SC lateral elements, is required to maintain both synapsis and dHJ-associated crossover recombination complexes (CRCs) during pachytene. The SC central region transverse-filament protein is also required to maintain CRCs. Reciprocally, the stability of the SC central region requires the continuous presence of CRCs effectively coupling synapsis to dHJ formation and desynapsis to resolution. However, dHJ protection and CRC maintenance can occur without end-to-end homologue synapsis mediated by the central element of the SC central region. We conclude that local ensembles of SC components are sufficient to enable crossover-specific dHJ resolution to ensure the linkage and segregation of homologous chromosomes.
Main
During meiotic prophase I, cohesin complexes connect sister chromatids and mediate their organization into linear arrays of chromatin loops tethered to a common axis2,5,7,8,9. These cohesin-based axes define interfaces for the pairing and synapsis of homologous chromosomes that culminates in the formation of SCs. An SC is a tripartite structure comprising the two juxtaposed homologue axes, now called lateral elements, connected by a central lattice of transverse filaments5,6. Extension of this lattice to achieve full synapsis requires an additional central element complex5,6,10 (Extended Data Fig. 1a). Meiotic recombination facilitates pairing and synapsis between homologous chromosomes and then connects them through crossing over. These connections are necessary for accurate segregation during the first meiotic division1. To this end, the DNA events of recombination are physically and functionally linked to underlying chromosome structures2. The protein complexes that catalyse DNA double-strand breaks (DSBs) and subsequent strand exchange are tethered to homologue axes. The ensuing joint molecule intermediates and their associated recombination complexes interact with the central region of the SC. A subset of recombination events is assigned a crossover fate with a tightly regulated distribution to ensure that each chromosome pair receives at least one2. At designated sites, nascent joint molecules mature into dHJs that then undergo biased resolution specifically into crossovers3,4. These steps occur in the context of the SC central region and associated CRCs. The post-synapsis roles of SC components in crossing over remain unclear, particularly whether the SC functions after dHJ formation to facilitate crossover-specific resolution.
Tang, S., Hariri, S., Bohn, R. et al.
Protecting double Holliday junctions ensures crossing over during meiosis.
Nature (2025). https://doi.org/10.1038/s41586-025-09555-1
Copyright: © 2025 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
Who in their right mind would consider designing a critical function such as the production of reproductive gametes, that needs to be suspended at a critical point for decades, requiring more complexity to minimise the risk of it failing - and then designing that process so it sometimes fails with serious, even fatal consequences for the resulting child?
Gamete production is just one of many such examples: from reproductive bottlenecks to skeletal weaknesses and brain vulnerabilities, our bodies bear the unmistakable stamp of compromise and accident, not foresight or perfection. This is the reality I explore in detail in my book, The Body of Evidence: How the Human Body Refutes Intelligent Design, part of my Unintelligent Design series.
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